Natalizumab

FDA, 26 Apr 2011

Accessed on 21 Nov 2011 from http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107198.htm.

Class:

Immunomodulator

(2)

New approaches in the management of multiple sclerosis.

FDA, 26 Apr 2011

Accessed on 21 Nov 2011 from http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107198.htm.

Target:

α4 integrins

(4)

Barten LJ, Allington DR, Procacci KA, Rivey MP

Drug Des Devel Ther. 2010; 4:343-66. Epub 2010 Nov 24. PMID: 21151622. Abstract

Leukocyte trafficking

(9)

Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?

Davenport RJ, Munday JR

Drug Discov Today. 2007 Jul; 12(13-14):569-76. Epub 2007 Jun 26. PMID: 17631252. Abstract

Status for MS:

Approved in the US for treating relapsing forms of MS (November, 2004)

(4)

New approaches in the management of multiple sclerosis.

Barten LJ, Allington DR, Procacci KA, Rivey MP

Drug Des Devel Ther. 2010; 4:343-66. Epub 2010 Nov 24. PMID: 21151622. Abstract

(15)

Tysabri

Biogen Idec, 2011

Accessed on 21 Nov 2011 from http://www.biogenidec.com/therapies_tysabri.aspx?ID=5589.

(263)

Medscape, 8 May 2015

Accessed on 12 May 2015 from http://www.medscape.com/viewarticle/844431.

Approved in the EU for treating highly active RRMS (June, 2006)

(263)

Medscape, 8 May 2015

Accessed on 12 May 2015 from http://www.medscape.com/viewarticle/844431.

Administration:

300 mg via intravenous infusion every four weeks (this information was provided by the manufacturer)

(14)

Extending Treatment Up To Eight Weeks With Infusion Medication Shown Safe and Effective in Patients with Multiple Sclerosis

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Extending the dose schedule (from 4 weeks to 5 to 8 weeks) did not reduce efficacy and was not associated with progressive multifocal leukoencephalopathy, as shown in a retrospective analysis involving 1964 individuals (meeting report, April 2015)

(259)

NYU Langone Medical Center, 22 Apr 2015

Accessed on 28 Apr 2015 from http://nyulangone.org/press-releases/extending-treatment-up-to-eight-weeks-with-infusion-medication-shown-safe-and-effective-in-patients-with-multiple-sclerosis.

; further analysis indicated that an 8-week dosing interval might reduce relapse rates and MRI lesions as compared with the 4-week interval (meeting report, October 2015)

(290)

New Data Show Longer Tysabri Dosing Interval in MS Is Feasible

Gever J, MedPage Today, 7 Oct 2015

Accessed on 13 Oct 2015 from http://www.medpagetoday.com/clinical-context/MultipleSclerosis/53960.

Review to assess whether the current approach for managing the risk of progressive multifocal leukoencephalopathy needs to be revised has been requested by the European Commission (May 2015)

(263)

New EMA Advice to Reduce PML Risk With Natalizumab (Tysabri) in MS

Medscape, 8 May 2015

Accessed on 12 May 2015 from http://www.medscape.com/viewarticle/844431.

; new guidelines have been issued by the European Medicines Agency (February 2016)

(318)

Jeffrey S, Medscape, 12 Feb 2016

Accessed on 16 Feb 2016 from http://www.medscape.com/viewarticle/858883.

Commercial:

Jointly developed by Elan Pharmaceuticals and Biogen Idec

(9)

Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?

Davenport RJ, Munday JR

Drug Discov Today. 2007 Jul; 12(13-14):569-76. Epub 2007 Jun 26. PMID: 17631252. Abstract

Clinical trials sponsored by Biogen Idec and Elan Pharmaceuticals

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Manufactured by Biogen Idec

(14)

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Distributed by Elan Pharmaceuticals

(14)

Biogen Idec to acquire full rights and control of Tysabri from Elan for upfront cash and contingent payments

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

; Biogen Idec will take full control of Tysabri in 2013

(65)

Biogen Idec, 6 Feb 2013

Accessed on 11 Feb 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1781970.

Available only through a special restricted distribution program (TOUCH), because of the risk of progressive multifocal leukoencephalopathy

(14)

Biogen Idec and Elan submit applications for first-line use of Tysabri in anti-JCV antibody negative patients with MS

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Marketing applications for first-line use in anti-JC virus antibody negative MS patients have been submitted to the US Food and Drug Administration and the European Medicines Agency by Biogen Idec and Elan (16 January 2013)

(62)

Biogen Idec, 16 Jan 2013

Accessed on 21 Jan 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1774946.

Full rights for and control of Tysabri will be acquired by Biogen Idec from Elan Pharmaceuticals for cash ($3.25 billion) and future contingent payments; the deal is expected to close by the end of the second quarter of 2013 (6 February 2013)

(65)

Biogen Idec to acquire full rights and control of Tysabri from Elan for upfront cash and contingent payments

Biogen Idec, 6 Feb 2013

Accessed on 11 Feb 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1781970.

Using some of the proceeds from the Tysabri restructuring, Elan Corporation will repurchase $1 billion of stock after the restructuring transaction with Biogen Idec is closed (22 February 2013)

(68)

Elan provides update post restructuring announcement of Tysabri collaboration

Elan Corporation, 22 Feb 2013

Accessed on 27 Feb 2013 from http://newsroom.elan.com/phoenix.zhtml?c=88326&p=irol-newsArticle&ID=1787913.

Full rights for and control of Tysabri have been purchased by Biogen Idec from Elan Pharmaceuticals (2 April 2013)

(83)

Biogen Idec completes purchase of full rights and control of Tysabri®

Biogen Idec, 2 Apr 2013

Accessed on 8 Apr 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1802638.

Biogen Idec, which markets Tysabri, has changed its name to Biogen (23 March 2015)

(264)

Biogen Idec Becomes Biogen

Biogen, 23 Mar 2015

Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.

Names

Name:

Natalizumab

Trade name:

Tysabri

(2)

FDA, 26 Apr 2011

Accessed on 21 Nov 2011 from http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107198.htm.

Synonyms:

Antegren

(1)

United States National Library of Medicine

Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Immunoglobulin G4 (human-mouse monoclonal AN100226 4-chain anti- human integrin 4), disulfide with human-mouse monoclonal AN100226 light chain, dimer

(1)

United States National Library of Medicine

Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Natalizumab

(1)

United States National Library of Medicine

Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Tysabri

(1)

United States National Library of Medicine

Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

UNII-3JB47N2Q2P

(1)

United States National Library of Medicine

Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Systematic name:

Immunoglobulin G4, anti-(human integrin alpha4) (human-mouse monoclonal AN100226 gamma4-chain), disulfide with human-mouse monoclonal AN100226 light chain, dimer

(1)

United States National Library of Medicine

Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Physiology

Class:

Immunomodulator

(2)

New approaches in the management of multiple sclerosis.

FDA, 26 Apr 2011

Accessed on 21 Nov 2011 from http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm107198.htm.

Target:

α4 integrins

(4)

Barten LJ, Allington DR, Procacci KA, Rivey MP

Drug Des Devel Ther. 2010; 4:343-66. Epub 2010 Nov 24. PMID: 21151622. Abstract

Leukocyte trafficking

(9)

Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?

Davenport RJ, Munday JR

Drug Discov Today. 2007 Jul; 12(13-14):569-76. Epub 2007 Jun 26. PMID: 17631252. Abstract

Properties:

Humanized monoclonal antibody against α4 integrin

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Humanized monoclonal antibody that contains the human framework regions and the murine complementarity-determining regions

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

(14)

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Molecular weight, 149 kDal

(14)

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Cell-bound drug has a different half-life than free drug, and cells can serve as a reservoir of drug (T. Sehr, meeting presentation, ECTRIMS, Oct 2011)

After intravenous administration, the mean half-life is 11 +/- 4 days

(14)

Clinical relevance of serum natalizumab concentration and anti-natalizumab antibodies in multiple sclerosis.

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Induces the production of antibodies against natalizumab in over half of treated patients (most of whom later revert to negative status for these antibodies); high titers of such antibodies (and corresponding low serum natalizumab concentrations) are associated with reduced efficacy of the drug

(35)

Vennegoor A, Rispens T, Strijbis E M, Seewann A, Uitdehaag B M, Balk LJ, Barkhof F, Polman CH, Wolbink G, Killestein J

Mult Scler. 2012 Sep 19. PMID: 22992450. Abstract

Binds to α4 integrin receptors on the surface of peripheral blood leukocytes, such that these receptors are more than 80% saturated 1 month after drug infusion

(22)

Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS.

Rudick RA, Sandrock A

Expert Rev Neurother. 2004 Jul; 4(4):571-80. PMID: 15853576. Abstract

Mechanisms/Effects

Human:

Exact mechanism unknown

(7)

About Tysabri

Biogen Idec and Elan Pharmaceuticals

Accessed on 21 Nov 2011 from http://www.tysabri.com/tysbProject/tysb.portal/_baseurl/threeColLayout/SCSRepository/en_US/tysb/home/about-tysabri/index.xml.

Binds to α4 integrins, integral membrane proteins that are expressed by leukocytes and mediate cell adhesion

(9)

Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?

Davenport RJ, Munday JR

Drug Discov Today. 2007 Jul; 12(13-14):569-76. Epub 2007 Jun 26. PMID: 17631252. Abstract

(14)

Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS.

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

(22)

Rudick RA, Sandrock A

Expert Rev Neurother. 2004 Jul; 4(4):571-80. PMID: 15853576. Abstract

Is thought to inhibit the binding of circulating immune cells to the blood brain barrier (a process that is mediated by α4 integrin)

(17)

Cutting edge: Natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis.

Coisne C, Mao W, Engelhardt B

J Immunol. 2009 May 15; 182(10):5909-13. PMID: 19414741. Abstract

Is thought to inhibit leukocyte adhesion and transmigration across the endothelium into inflammed tissue by blocking the interaction of α4 integrins with their receptors

(14)

VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells.

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Blocks the integrin dimer termed very late antigen-4 and thereby inhibits lymphocyte trafficking into the central nervous system, but promotes alternative routes for migrating across the blood-brain barrier that involve T cell rolling mediated by P-selectin glycoprotein ligand-1 and Th17 adhesion mediated by myeloma cell adhesion molecule

(211)

Schneider-Hohendorf T, Rossaint J, Mohan H, Böning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, et al.

J Exp Med. 2014 Aug 25; 211(9):1833-46. Epub 2014 Aug 18. PMID: 25135296. Abstract

T cells from individuals under long-term treatment display enhanced rolling mediated by P-selectin glycoprotein ligand-1, as well as some adhesion, on primary human endothelial cells in vitro, even with blockade of very late antigen-4

(211)

VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells.

Schneider-Hohendorf T, Rossaint J, Mohan H, Böning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, et al.

J Exp Med. 2014 Aug 25; 211(9):1833-46. Epub 2014 Aug 18. PMID: 25135296. Abstract

TH17 cells [which express myeloma cell adhesion molecule (MCAM)] from individuals under long-term treatment still adhere to primary human endothelial cells in vitro; such adhesion is not prevented by blockade of very late antigen-4 (VLA-4), but is prevented if by blockade of VLA-4 and MCAM

(211)

VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells.

Schneider-Hohendorf T, Rossaint J, Mohan H, Böning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, et al.

J Exp Med. 2014 Aug 25; 211(9):1833-46. Epub 2014 Aug 18. PMID: 25135296. Abstract

Long-term treatment is associated with increased expression of myeloma cell adhesion molecule, but a lack of the integrin alpha subunit CD49d, on T cells in the cerebrospinal fluid

(211)

VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells.

Schneider-Hohendorf T, Rossaint J, Mohan H, Böning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, et al.

J Exp Med. 2014 Aug 25; 211(9):1833-46. Epub 2014 Aug 18. PMID: 25135296. Abstract

Long-term treatment is associated with increased expression of P-selectin glycoprotein ligand-1 (which binds the adhesion molecule P-selectin and mediates rolling on endothelial cell surfaces in blood vessels) on peripheral T cells

(211)

VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells.

Schneider-Hohendorf T, Rossaint J, Mohan H, Böning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, et al.

J Exp Med. 2014 Aug 25; 211(9):1833-46. Epub 2014 Aug 18. PMID: 25135296. Abstract

Long-term treatment is associated with normal central- to effector-memory T cell ratios in the cerebrospinal fluid

(211)

VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells.

Schneider-Hohendorf T, Rossaint J, Mohan H, Böning D, Breuer J, Kuhlmann T, Gross CC, Flanagan K, Sorokin L, Vestweber D, et al.

J Exp Med. 2014 Aug 25; 211(9):1833-46. Epub 2014 Aug 18. PMID: 25135296. Abstract

Reduces levels of soluble vascular cell adhesion molecule 1, a ligand for α4β1 integrin that is upregulated in MS, in MS patients

(19)

Natalizumab treatment reduces endothelial activity in MS patients.

Millonig A, Hegen H, Di Pauli F, Ehling R, Gneiss C, Hoelzl M, Künz B, Lutterotti A, Rudzki D, Berger T, et al.

J Neuroimmunol. 2010 Oct 8; 227(1-2):190-4. Epub 2010 Aug 23. PMID: 20739072. Abstract

Partially inhibits the ability of soluble vascular cell adhesion molecule 1 to impair integrity of the brain endothelial barrier, as shown by studies with primary human brain microvascular endothelial cells

(256)

Soluble VCAM-1 impairs human brain endothelial barrier integrity via integrin α-4-transduced outside-in signalling.

Haarmann A, Nowak E, Deiß A, van der Pol S, Monoranu C-M, Kooij G, Müller N, van der Valk P, Stoll G, de Vries HE, et al.

Acta Neuropathol. 2015 Mar 27. Epub 2015 Mar 27. PMID: 25814153. Abstract

Increases peripheral accumulation of newly-produced T and B lymphocytes because of a low level of migration across endothelial cells, and because of a high level of release, in MS patients

(31)

Peripheral accumulation of newly produced T and B lymphocytes in natalizumab-treated multiple sclerosis patients.

Zanotti C, Chiarini M, Serana F, Sottini A, Garrafa E, Torri F, Caimi L, Rasia S, Capra R, Imberti L

Clin Immunol. 2012 Jul 21; 145(1):19-26. PMID: 22892399. Abstract

Reduces counts of leukocytes, CD4+ and CD8+ T cells, B cells, and plasma cells in the cerebrospinal fluid in MS patients, in agreement with the idea that the drug weakens immune surveillance in the central nervous system

(20)

Immune surveillance in multiple sclerosis patients treated with natalizumab.

Stüve O, Marra CM, Jerome KR, Cook L, Cravens PD, Cepok S, Frohman EM, Phillips TJ, Arendt G, Hemmer B, et al.

Ann Neurol. 2006 May; 59(5):743-7. PMID: 16634029. Abstract

Decreases the ratio of CD4+ T cells to CD8+ T cells in the cerebrospinal fluid in MS patients

(21)

Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis.

Stüve O, Marra CM, Bar-Or A, Niino M, Cravens PD, Cepok S, Frohman EM, Phillips TJ, Arendt G, Jerome KR, et al.

Arch Neurol. 2006 Oct; 63(10):1383-7. PMID: 17030653. Abstract

Treatment (every 4 weeks for 48 weeks) strongly increases peripheral CD4 counts, which then decline to baseline when treatment is interrupted (for 12 weeks), and then rise again when treatment is reinitiated, as shown in a study of individuals with relapsing MS

(265)

CD4 cell response to interval therapy with natalizumab.

Berkovich R, Togasaki DM, Cen SY, Steinman L

Ann Clin Transl Neurol. 2015 May; 2(5):570-4. Epub 2015 Mar 06. PMID: 26000328. Abstract

Concentrations in the cerebrospinal fluid show high interindividual variability in natalizumab-treated individuals with MS

(242)

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis.

Harrer A, Pilz G, Wipfler P, Oppermann K, Sellner J, Hitzl W, Haschke-Becher E, Afazel S, Rispens T, van der Kleij D, et al.

Clin Exp Immunol. 2015 Jan 20. PMID: 25603898. Abstract

Concentrations of free natalizumab in the cerebrospinal fluid (CSF) do not correlate with the CD4+/CD8+ T cell ratio in the CSF in natalizumab-treated individuals with MS

(242)

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis.

Harrer A, Pilz G, Wipfler P, Oppermann K, Sellner J, Hitzl W, Haschke-Becher E, Afazel S, Rispens T, van der Kleij D, et al.

Clin Exp Immunol. 2015 Jan 20. PMID: 25603898. Abstract

Cell-bound natalizumab levels do not correlate with the CD4+/CD8+ T cell ratio in the cerebrospinal fluid in natalizumab-treated individuals with MS

(242)

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis.

Harrer A, Pilz G, Wipfler P, Oppermann K, Sellner J, Hitzl W, Haschke-Becher E, Afazel S, Rispens T, van der Kleij D, et al.

Clin Exp Immunol. 2015 Jan 20. PMID: 25603898. Abstract

Associated with an increased number of circulating white blood cells, especially B lymphocytes, even after prolonged therapy in MS patients

(61)

Immune cells after prolonged Natalizumab therapy: implications for effectiveness and safety.

Marousi S, Karkanis I, Kalamatas T, Travasarou M, Paterakis G, Karageorgiou CE

Acta Neurol Scand. 2013 Jan 11. PMID: 23311457. Abstract

Associated with a decreased circulating CD4:CD8 cell ratio even after prolonged therapy, specifically in MS patients who exhibit a long-term response to therapy

(61)

Immune cells after prolonged Natalizumab therapy: implications for effectiveness and safety.

Marousi S, Karkanis I, Kalamatas T, Travasarou M, Paterakis G, Karageorgiou CE

Acta Neurol Scand. 2013 Jan 11. PMID: 23311457. Abstract

Long-term treatment is associated with a reduction in the percentage of CD4+ T cells that express L-selectin

(104)

L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients.

Schwab N, Schneider-Hohendorf T, Posevitz V, Breuer J, Göbel K, Windhagen S, Brochet B, Vermersch P, Lebrun-Frenay C, Posevitz-Fejfár A, et al.

Neurology. 2013 Sep 3; 81(10):865-71. Epub 2013 Aug 07. PMID: 23925765. Abstract

Associated with a reduction in the percentage of CD4+ T cells that express L-selectin (which is involved in leukocyte rolling and transmigration) as compared with first-line MS treatments

(280)

Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells.

Spadaro M, Caldano M, Marnetto F, Lugaresi A, Bertolotto A

J Neuroinflammation. 2015; 12:146. Epub 2015 Aug 12. PMID: 26259673. Abstract

Associated with a reduction in the percentage of CD4+ T cells that express L-selectin that is apparent in the first year of treatment, persists, and then reverses when treatment ends, as shown in a longitudinal study

(280)

Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells.

Spadaro M, Caldano M, Marnetto F, Lugaresi A, Bertolotto A

J Neuroinflammation. 2015; 12:146. Epub 2015 Aug 12. PMID: 26259673. Abstract

Induces changes in inflammatory cytokine levels in RRMS patients

(18)

Treatment with natalizumab in relapsing-remitting multiple sclerosis patients induces changes in inflammatory mechanism.

Ramos-Cejudo J, Oreja-Guevara C, Stark Aroeira L, Rodriguez de Antonio L, Chamorro B, Diez-Tejedor E

J Clin Immunol. 2011 Aug; 31(4):623-31. Epub 2011 Apr 14. PMID: 21491095. Abstract

Selectively increases levels of effector-memory T cells in the blood, but does not affect the activation state of T cells in the blood, and does not selectively increase myelin-reactive T cells, in MS patients

(52)

Effect of Natalizumab on Circulating CD4(+) T-Cells in Multiple Sclerosis.

Börnsen L, Romme Christensen J, Ratzer R, Oturai A B, Sørensen P S, Søndergaard H B, Sellebjerg F

PLoS One. 2012; 7(11):e47578. Epub 2012 Nov 30. PMID: 23226199. Abstract

Increases tumor necrosis factor-alpha mRNA expression in T cells, but does not affect the expression of other tested effector cytokines or transcription factors, in MS patients

(52)

Effect of Natalizumab on Circulating CD4(+) T-Cells in Multiple Sclerosis.

Börnsen L, Romme Christensen J, Ratzer R, Oturai A B, Sørensen P S, Søndergaard H B, Sellebjerg F

PLoS One. 2012; 7(11):e47578. Epub 2012 Nov 30. PMID: 23226199. Abstract

Decreases the expression of the co-stimulatory molecule CD134 on CD26(HIGH)CD4(+) T cells, but otherwise does not affect the response of CD4(+) T cells to myelin basic protein, in MS patients

(52)

Effect of Natalizumab on Circulating CD4(+) T-Cells in Multiple Sclerosis.

Börnsen L, Romme Christensen J, Ratzer R, Oturai A B, Sørensen P S, Søndergaard H B, Sellebjerg F

PLoS One. 2012; 7(11):e47578. Epub 2012 Nov 30. PMID: 23226199. Abstract

Restricts (and thereby appears to normalize) the T cell receptor repertoire, which is expanded in individuals with MS

(115)

Natalizumab affects the T-cell receptor repertoire in patients with multiple sclerosis.

Warnke C, Mausberg AK, Stettner M, Dehmel T, Nekrich L, Meyer Zu Horste G, Hartung H-P, Fogdell-Hahn A, Adams O, Kieseier BC

Neurology. 2013 Sep 18. PMID: 24049136. Abstract

(116)

A bird's-eye view of T cells during natalizumab therapy.

Hohlfeld R, Stüve O

Neurology. 2013 Sep 18. PMID: 24049137. Abstract

In vitro, decreases the expression of the co-stimulatory molecule CD134 on myelin basic protein-reactive CD26(HIGH)CD4(+) T-cells

(52)

Effect of Natalizumab on Circulating CD4(+) T-Cells in Multiple Sclerosis.

Börnsen L, Romme Christensen J, Ratzer R, Oturai A B, Sørensen P S, Søndergaard H B, Sellebjerg F

PLoS One. 2012; 7(11):e47578. Epub 2012 Nov 30. PMID: 23226199. Abstract

Affects the expression pattern of 10 microRNAs in B lymphocytes from RRMS patients

(28)

Altered microRNA expression in B lymphocytes in multiple sclerosis: Towards a better understanding of treatment effects.

Sievers C, Meira M, Hoffmann F, Fontoura P, Kappos L, Lindberg RLP

Clin Immunol. 2012 Jul; 144(1):70-9. Epub 2012 May 02. PMID: 22659298. Abstract

Downregulates expression of the microRNA miR-126, which is increased during relapses, in CD4+ T cells from individuals with MS

(155)

MiR-126: a novel route for natalizumab action?

Meira M, Sievers C, Hoffmann F, Derfuss T, Kuhle J, Kappos L, Lindberg RLP

Mult Scler. 2014 Mar 5. PMID: 24598267. Abstract

Treatment is associated with downregulation of the microRNA miR-126 (a non-coding RNA that reduces expression of target genes) and upregulation of proteins POU2AF1 and Spi-B; POU2AF1 regulates Spi-B, a transcription factor that interacts with promotor/enhancer sequences of the JC virus (the cause of progressive multifocal leukoencephalopathy)

(155)

MiR-126: a novel route for natalizumab action?

Meira M, Sievers C, Hoffmann F, Derfuss T, Kuhle J, Kappos L, Lindberg RLP

Mult Scler. 2014 Mar 5. PMID: 24598267. Abstract

Modifies the expression of certain microRNAs (let-7c, miR-125a-5p, and miR-642), based on a study of blood samples from 19 individuals with RRMS

(184)

Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients.

Muñoz-Culla M, Irizar H, Castillo-Triviño T, Sáenz-Cuesta M, Sepúlveda L, Lopetegi I, de Munain LA, Olascoaga J, Baranzini SE, Otaegui D

Mult Scler. 2014 May 22. PMID: 24852919. Abstract

Treatment downregulates microRNA-17 expression, which is upregulated during relapse, in CD4+ T cells from individuals with RRMS

(188)

Unraveling Natalizumab Effects on Deregulated miR-17 Expression in CD4(+) T Cells of Patients with Relapsing-Remitting Multiple Sclerosis.

Meira M, Sievers C, Hoffmann F, Rasenack M, Kuhle J, Derfuss T, Kappos L, Lindberg RLP

J Immunol Res. 2014; 2014:897249. Epub 2014 May 12. PMID: 24901013. Abstract

Treatment downregulates microRNA-17 expression, which in turn upregulates target genes PTEN, BIM, E2F1, and p21, in CD4+ T cells from individuals with RRMS; inhibition of microRNA-17 in vitro inhibits activation and proliferation of CD4+ T cells

(188)

Unraveling Natalizumab Effects on Deregulated miR-17 Expression in CD4(+) T Cells of Patients with Relapsing-Remitting Multiple Sclerosis.

Meira M, Sievers C, Hoffmann F, Rasenack M, Kuhle J, Derfuss T, Kappos L, Lindberg RLP

J Immunol Res. 2014; 2014:897249. Epub 2014 May 12. PMID: 24901013. Abstract

Restores patterns of microRNA expression that are dysregulated in MS, as shown by a longitudinal study of 17 individuals with RRMS and 18 matched healthy controls

(244)

Natalizumab restores aberrant miRNA expression profile in multiple sclerosis and reveals a critical role for miR-20b.

Ingwersen J, Menge T, Wingerath B, Kaya D, Graf J, Prozorovski T, Keller A, Backes C, Beier M, Scheffler M, et al.

Ann Clin Transl Neurol. 2015 Jan; 2(1):43-55. Epub 2014 Dec 05. PMID: 25642434. Abstract

Upregulates expression of microRNAs miR-18a, miR-20b, miR-29a, and miR-103 (which are downregulated in MS), and downregulates miR-326, as shown by a longitudinal study of 17 individuals with RRMS

(244)

Natalizumab restores aberrant miRNA expression profile in multiple sclerosis and reveals a critical role for miR-20b.

Ingwersen J, Menge T, Wingerath B, Kaya D, Graf J, Prozorovski T, Keller A, Backes C, Beier M, Scheffler M, et al.

Ann Clin Transl Neurol. 2015 Jan; 2(1):43-55. Epub 2014 Dec 05. PMID: 25642434. Abstract

Decreases expression of the proinflammatory micro-RNA miR-155, as shown by studies of monocytes isolated from treated versus untreated individuals with MS

(307)

Effects of fumarates on circulating and CNS myeloid cells in multiple sclerosis.

Michell-Robinson MA, Moore CS, Healy LM, Osso LA, Zorko N, Grouza V, Touil H, Poliquin-Lasnier L, Trudelle A-M, Giacomini PS, et al.

Ann Clin Transl Neurol. 2016 Jan; 3(1):27-41. Epub 2015 Dec 02. PMID: 26783548. Abstract

Decreases expression of the antioxidant genes HMOX1 and OSGIN1, as shown by studies of monocytes isolated from treated versus untreated individuals with MS

(307)

Effects of fumarates on circulating and CNS myeloid cells in multiple sclerosis.

Michell-Robinson MA, Moore CS, Healy LM, Osso LA, Zorko N, Grouza V, Touil H, Poliquin-Lasnier L, Trudelle A-M, Giacomini PS, et al.

Ann Clin Transl Neurol. 2016 Jan; 3(1):27-41. Epub 2015 Dec 02. PMID: 26783548. Abstract

Associated with the presence of JC virus DNA in circulating CD34+ stem cells and CD19+ (B lymphocyte) cells (as well as higher levels of CD34+ cells, which are mobilized by natalizumab into the peripheral circulation) in a prospective study that compared individuals with MS beginning or undergoing natalizumab treatment with healthy volunteers, providing a link between the effects of natalizumab and progressive multifocal leukoencephalopathy

(163)

JC Virus in CD34+ and CD19+ Cells in Patients With Multiple Sclerosis Treated With Natalizumab.

Frohman EM, Monaco M C, Remington G, Ryschkewitsch C, Jensen PN, Johnson K, Perkins M, Liebner J, Greenberg B, Monson N, et al.

JAMA Neurol. 2014 Mar 24. PMID: 24664166. Abstract

(164)

New Clues to Link Between MS Drug Tysabri and Rare Brain Disease

Goodman B, WebMD, 25 Mar 2014

Accessed on 1 Apr 2014 from http://www.webmd.com/multiple-sclerosis/news/20140325/new-clues-to-link-between-ms-drug-tysabri-and-rare-brain-disease.

Long-term therapy might affect T2 intensity of deep gray matter structures, as visualized by MRI, suggesting a potential effect of the drug beyond its anti-inflammatory role

(30)

Analysis of T2 intensity by magnetic resonance imaging of deep gray matter nuclei in multiple sclerosis patients: effect of immunomodulatory therapies.

Pawate S, Wang L, Song Y, Sriram S

J Neuroimaging. 2012 Apr; 22(2):137-44. Epub 2011 Jun 24. PMID: 21707826. Abstract

May counteract the altered metabolism of amyloid precursor protein (APP) that occurs in MS [which results in reduced levels of amyloid beta and soluble APP fragments in cerebrospinal fluid (CSF)], as determined by analysis of CSF samples from MS patients at baseline and after 1 to 2 years of treatment

(45)

Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis.

Augutis K, Axelsson M, Portelius E, Brinkmalm G, Andreasson U, Gustavsson MK, Malmeström C, Lycke J, Blennow K, Zetterberg H, et al.

Mult Scler. 2012 Oct 15. PMID: 23069872. Abstract

Inhibits intrathecal antibody production patients in some MS patients

(46)

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy.

Harrer A, Tumani H, Niendorf S, Lauda F, Geis C, Weishaupt A, Kleinschnitz C, Rauer S, Kuhle J, Stangel M, et al.

Mult Scler. 2012 Oct 23. PMID: 23093485. Abstract

Reduces expression of endogenous retroviruses of the HERV-W family, which have been linked with MS pathogenesis, as shown in a longitudinal cohort study of individuals with MS (none of whom relapsed during this study)

(99)

Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: a longitudinal cohort study.

Arru G, Leoni S, Pugliatti M, Mei A, Serra C, Delogu L G, Manetti R, Dolei A, Sotgiu S, Mameli G

Mult Scler. 2013 Jul 22. PMID: 23877972. Abstract

Reduces the antibody response against the human endogenous retrovirus HERV-Wenv(73-88) peptide (but not the response to peptides from Epstein Barr virus or Mycobacterium avium ss. Paratuberculosis) in individuals with MS after two years of treatment

(279)

Natalizumab modulates the humoral response against HERV-Wenv73-88 in a follow-up study of Multiple Sclerosis patients.

Arru G, Caggiu E, Leoni S, Mameli G, Pugliatti M, Sechi G P, Sechi LA

J Neurol Sci. 2015 Jul 8. PMID: 26190523. Abstract

Mildly upregulates interleukin 2 (IL-2), interferon gamma, and IL-17 in activated primary CD4+ T cells (which were propagated ex vivo) from healthy donors

(55)

Natalizumab exerts direct signaling capacity and supports a pro-inflammatory phenotype in some patients with multiple sclerosis.

Benkert TF, Dietz L, Hartmann EM, Leich E, Rosenwald A, Serfling E, Buttmann M, Berberich-Siebelt F

PLoS One. 2012; 7(12):e52208. Epub 2012 Dec 20. PMID: 23284936. Abstract

Upregulates interleukin 2 (IL-2), interferon gamma, and IL-17 (a pro-inflammatory phenotype) in peripheral blood mononuclear cells from some treated RRMS patients within 24 hours after the first infusion of drug

(55)

Natalizumab exerts direct signaling capacity and supports a pro-inflammatory phenotype in some patients with multiple sclerosis.

Benkert TF, Dietz L, Hartmann EM, Leich E, Rosenwald A, Serfling E, Buttmann M, Berberich-Siebelt F

PLoS One. 2012; 7(12):e52208. Epub 2012 Dec 20. PMID: 23284936. Abstract

Natalizumab or interferon beta treatment is associated with significantly reduced serum levels of a "cytokine signature" [a summed value of levels of tumor necrosis factor-alpha, interferon gamma, S100B, interleukin-1beta (IL-1beta), IL-6, IL-8, IL-17, and IL-23] in individuals with MS as compared with levels in drug naïve individuals with MS

(198)

The use of cytokine signature patterns: separating drug naïve, interferon and natalizumab-treated multiple sclerosis patients.

O'Connell KE, Mok T, Sweeney B, Ryan AM, Dev KK

Autoimmunity. 2014 Jun 30:1-7. PMID: 24974887. Abstract

Natalizumab treatment is associated with reduced serum levels of pro-inflammatory cytokines as compared with interferon beta treatment in individuals with MS

(198)

The use of cytokine signature patterns: separating drug naïve, interferon and natalizumab-treated multiple sclerosis patients.

O'Connell KE, Mok T, Sweeney B, Ryan AM, Dev KK

Autoimmunity. 2014 Jun 30:1-7. PMID: 24974887. Abstract

Enhances phosphorylation of ERK in stimulated human Jurkat (CD4+ T cell line) cells and in primary CD4+ T cells, indicating that natalizumab causes signaling effects that resemble natural integrin signaling

(55)

Natalizumab exerts direct signaling capacity and supports a pro-inflammatory phenotype in some patients with multiple sclerosis.

Benkert TF, Dietz L, Hartmann EM, Leich E, Rosenwald A, Serfling E, Buttmann M, Berberich-Siebelt F

PLoS One. 2012; 7(12):e52208. Epub 2012 Dec 20. PMID: 23284936. Abstract

Decreases the surface expression of CD49d (integrin α4) by causing the rapid internalization and degradation of CD49d, based on experiments using the human CD4+ T cell line Jurkat and human peripheral blood mononuclear cells

(55)

Natalizumab exerts direct signaling capacity and supports a pro-inflammatory phenotype in some patients with multiple sclerosis.

Benkert TF, Dietz L, Hartmann EM, Leich E, Rosenwald A, Serfling E, Buttmann M, Berberich-Siebelt F

PLoS One. 2012; 7(12):e52208. Epub 2012 Dec 20. PMID: 23284936. Abstract

Reduces levels of chitinase-3-like protein 1, as well as the inflammation-related proteins Ig mu chain C region and haptoglobin, in the cerebrospinal fluid of RRMS patients, as shown by profiling proteomics experiments

(64)

Effects of natalizumab treatment on the CSF proteome of multiple sclerosis patients.

Stoop MP, Singh V, Stingl C, Martin R, Khademi M, Olsson T, Hintzen R, Luider TM

J Proteome Res. 2013 Jan 22. PMID: 23339689. Abstract

Normalizes levels of soluble triggering receptor expressed on myeloid cells-2 in the cerebrospinal fluid, which are increased in individuals with RRMS, SPMS, or PPMS

(304)

Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone.

Öhrfelt A, Axelsson M, Malmeström C, Novakova L, Heslegrave A, Blennow K, Lycke J, Zetterberg H

Mult Scler. 2016 Jan 11. PMID: 26754805. Abstract

Normalizes the blood level of the transcription factor TBX21, which is decreased in individuals with MS

(305)

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies.

McKay FC, Gatt PN, Fewings N, Parnell GP, Schibeci SD, Basuki MAI, Powell JE, Goldinger A, Fabis-Pedrini MJ, Kermode AG, et al.

Clin Immunol. 2016 Jan 4; 163:96-107. PMID: 26762769. Abstract

May slightly reduce anti-JC virus and anti-varicella-zoster virus antibody levels, as shown by analysis of stored sera from a Swedish national MS cohort

(74)

Changes to anti-JCV antibody levels in a Swedish national MS cohort.

Warnke C, Ramanujam R, Plavina T, Bergström T, Goelz S, Subramanyam M, Kockum I, Rahbar A, Kieseier BC, Holmén C, et al.

J Neurol Neurosurg Psychiatry. 2013 Mar 5. PMID: 23463870. Abstract

May reduce anti-JC virus antibody levels, but does not affect the seroprevalence of anti-JC virus antibodies, as shown in a study of a Finnish MS cohort

(282)

Anti-JC virus seroprevalence in a Finnish MS cohort.

Kolasa M, Hagman S, Verkkoniemi-Ahola A, Airas L, Koivisto K, Elovaara I

Acta Neurol Scand. 2015 Sep 8. PMID: 26347001. Abstract

Does not appear to affect anti-JC virus antibody prevalence, as shown by a cross-sectional study of a multinational MS cohort

(75)

Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort.

Olsson T, Achiron A, Alfredsson L, Berger T, Brassat D, Chan A, Comi G, Eraksoy M, Hegen H, Hillert J, et al.

Mult Scler. 2013 Mar 4. PMID: 23459571. Abstract

Appears to increase the anti-JC virus antibody titer substantially over time, as shown in a longitudinal study involving 485 natalizumab-treated indivduals with MS, 340 of whom had repeat antibody testing

(293)

Anti-JC virus antibody titres increase over time with natalizumab treatment.

Raffel J, Gafson AR, Malik O, Nicholas R

Mult Scler. 2015 Oct 8. PMID: 26449743. Abstract

Associated with an increase in the incidence of elevated levels of anti-varicella-zoster virus IgG

(255)

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis.

Kohlmann R, Salmen A, Chan A, Knabbe C, Diekmann J, Brockmeyer N, Skaletz-Rorowski A, Michalik C, Gold R, Überla K

Mult Scler. 2015 Mar 31. PMID: 25828755. Abstract

Lowers serum IgM and IgG levels in MS patients, as shown in both cross-sectional and longitudinal analyses

(76)

Natalizumab treatment decreases serum IgM and IgG levels in multiple sclerosis patients.

Selter RC, Biberacher V, Grummel V, Buck D, Eienbröker C, Oertel WH, Berthele A, Tackenberg B, Hemmer B

Mult Scler. 2013 Feb 25. Epub 1969 Dec 31. PMID: 23439578. Abstract

Reduces or eliminates oligoclonal IgG bands from cerebrospinal fluid, as shown by a prospective, two-year longitudinal study of 24 individuals with MS

(195)

Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: A longitudinal study.

Mancuso R, Franciotta D, Rovaris M, Caputo D, Sala A, Hernis A, Agostini S, Calvo M, Clerici M

Mult Scler. 2014 Jun 16. PMID: 24948690. Abstract

Reduces intrathecal IgG production, as shown by a prospective, two-year longitudinal study of 24 individuals with MS

(195)

Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: A longitudinal study.

Mancuso R, Franciotta D, Rovaris M, Caputo D, Sala A, Hernis A, Agostini S, Calvo M, Clerici M

Mult Scler. 2014 Jun 16. PMID: 24948690. Abstract

Induces the production of anti-natalizumab antibodies (which are associated with reduced drug efficacy) in a subset of patients soon after treatment onset (most commonly, within 1 month); in a study of 134 MS patients, 15.7% produced antibodies, with 8.2% persistently positive

(93)

Early development of anti-natalizumab antibodies in MS patients.

Oliver-Martos B, Orpez-Zafra T, Urbaneja P, Maldonado-Sanchez R, Leyva L, Fernández O

J Neurol. 2013 Jun 14. Epub 2013 Jun 14. PMID: 23765090. Abstract

Can induce the production of anti-natalizumab antibodies (which reduce the drug's effectiveness); the risk of developing such antibodies is higher in individuals who smoke

(134)

Smokers run increased risk of developing anti-natalizumab antibodies.

Hedström A, Alfredsson L, Lundkvist Ryner M, Fogdell-Hahn A, Hillert J, Olsson T

Mult Scler. 2013 Dec 5. PMID: 24311118. Abstract

Increases total natural killer cells, as well as the subset of CD56(bright) (immature) natural killer cells, in peripheral blood of MS patients

(78)

The role of natural killer cells in multiple sclerosis and their therapeutic implications.

Chanvillard C, Jacolik RF, Infante-Duarte C, Nayak RC

Front Immunol. 2013; 4:63. Epub 2013 Mar 13. PMID: 23493880. Abstract

Reduces expression of natural killer cell receptor 1 in peripheral blood mononuclear cells; such expression is increased in individuals with MS relative to healthy controls

(212)

Are natural killer cells involved in multiple sclerosis etiology? Evidences from NKp46/NCR1 receptor modulation in an observational study.

Galuppo M, Giacoppo S, Sessa E, Bramanti P, Mazzon E

J Neurol Sci. 2014 Jul 30. PMID: 25115502. Abstract

Increases the absolute numbers of cells in all primary lymphocyte populations in the blood, especially natural killer cells and B cells, as shown by studies of individuals with RRMS before and after 1 year of treatment

(133)

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

Mellergård J, Edström M, Jenmalm MC, Dahle C, Vrethem M, Ernerudh J

PLoS One. 2013; 8(12):e81685. Epub 2013 Dec 02. PMID: 24312575. Abstract

Increases the proportion of memory and presumed regulatory B cell subsets and CD3(-)CD56(dim) cytotoxic natural killer cells in the blood lymphocyte population, but decreases the proportion of CD3(-)CD56(bright) regulatory natural killer cells, as shown by studies of individuals with RRMS before and after 1 year of treatment

(133)

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

Mellergård J, Edström M, Jenmalm MC, Dahle C, Vrethem M, Ernerudh J

PLoS One. 2013; 8(12):e81685. Epub 2013 Dec 02. PMID: 24312575. Abstract

Increases the responsiveness of T cells from individuals with RRMS to recall antigens and mitogens

(133)

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

Mellergård J, Edström M, Jenmalm MC, Dahle C, Vrethem M, Ernerudh J

PLoS One. 2013; 8(12):e81685. Epub 2013 Dec 02. PMID: 24312575. Abstract

Results in a stable increase in lymphocytes (which is greater than the increase in overall white blood cells) in peripheral blood over long-term treatment in RRMS patients

(141)

Long term follow up of peripheral lymphocyte subsets in a cohort of multiple sclerosis patients treated with natalizumab.

Koudriavtseva T, Sbardella E, Trento E, Bordignon V, D'Agosto G, Cordiali-Fei P

Clin Exp Immunol. 2014 Jan 6. PMID: 24387139. Abstract

Results in a stable increase in lymphocytes in peripheral blood over long-term treatment in RRMS patients, such that the increase in B cells is greater than that of T cells or natural killer cells

(141)

Long term follow up of peripheral lymphocyte subsets in a cohort of multiple sclerosis patients treated with natalizumab.

Koudriavtseva T, Sbardella E, Trento E, Bordignon V, D'Agosto G, Cordiali-Fei P

Clin Exp Immunol. 2014 Jan 6. PMID: 24387139. Abstract

Does not significantly alter the CD4/CD8 ratio over long-term treatment in RRMS patients

(141)

Long term follow up of peripheral lymphocyte subsets in a cohort of multiple sclerosis patients treated with natalizumab.

Koudriavtseva T, Sbardella E, Trento E, Bordignon V, D'Agosto G, Cordiali-Fei P

Clin Exp Immunol. 2014 Jan 6. PMID: 24387139. Abstract

Reduces the peripheral blood population of CD49d+ (α4 integrin subunit+) T cells, and this reduction is greater for regulatory T cells versus Th1 or Th17 cell subsets, as shown in a study of 27 natalizumab-naïve and 8 natalizumab-treated individuals with MS

(321)

Disrupted balance of T cells under natalizumab treatment in multiple sclerosis.

Kimura K, Nakamura M, Sato W, Okamoto T, Araki M, Lin Y, Murata M, Takahashi R, Yamamura T

Neurol Neuroimmunol Neuroinflamm. 2016 Apr; 3(2):e210. Epub 2016 Mar 03. PMID: 27006971. Abstract

Increases the expression of proinflammatory genes (TBX21, RORC, interferon γ, and interleukin 17A) and reduces the expression of FOXP3 in CD49d+ memory CD4 T cells, as shown in a study of sorted cells from natalizumab-naïve and natalizumab-treated individuals with MS

(321)

Disrupted balance of T cells under natalizumab treatment in multiple sclerosis.

Kimura K, Nakamura M, Sato W, Okamoto T, Araki M, Lin Y, Murata M, Takahashi R, Yamamura T

Neurol Neuroimmunol Neuroinflamm. 2016 Apr; 3(2):e210. Epub 2016 Mar 03. PMID: 27006971. Abstract

Increases the proportion of Th17 cells in peripheral blood, and this proportion falls to baseline when natalizumab is withdrawn (and becomes nearly undetectable during relapses that occur during washout), as shown in a study of 57 individuals with MS

(323)

Th17 cells: A prognostic marker for MS rebound after natalizumab cessation?

Haas J, Schneider K, Schwarz A, Korporal-Kuhnke M, Faller S, von Glehn F, Jarius S, Wildemann B

Mult Scler. 2016 Mar 21. PMID: 27003947. Abstract

Increases serum levels of endogenous secretory receptor for advanced glycation end-products (esRAGE); serum esRAGE levels are reduced during clinical relapse

(229)

Disease modifying drugs modulate endogenous secretory receptor for advanced glycation end-products, a new biomarker of clinical relapse in multiple sclerosis.

Sternberg Z, Sternberg D, Drake A, Chichelli T, Yu J, Hojnacki D

J Neuroimmunol. 2014 Sep 15; 274(1-2):197-201. Epub 2014 Jul 15. PMID: 25064498. Abstract

Does not affect the frequency of CD27+CD43+ B1 cells, which is reduced in RRMS

(181)

B1 cells are unaffected by immune modulatory treatment in remitting-relapsing multiple sclerosis patients.

Rovituso D, Heller S, Schroeter M, Kleinschnitz C, Kuerten S

J Neuroimmunol. 2014 Apr 24. PMID: 24814390. Abstract

Reduces the frequency of circulating plasmacytoid dendritic cells by 25 to 50%, but does not affect the frequency of myeloid dendritic cells, in individuals with MS, as shown by a cross-sectional observational study

(209)

Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a cross-sectional observational study in patients with multiple sclerosis.

Kivisäkk P, Francois K, Mbianda J, Gandhi R, Weiner HL, Khoury SJ

PLoS One. 2014; 9(7):e103716. Epub 2014 Jul 30. PMID: 25075741. Abstract

Reduces the frequency of circulating plasmacytoid dendritic cells (PDCs) in individuals with MS; the PDCs present exhibit a mature, activated phenotype as compared with those from untreated individuals, as shown by a cross-sectional observational study

(209)

Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a cross-sectional observational study in patients with multiple sclerosis.

Kivisäkk P, Francois K, Mbianda J, Gandhi R, Weiner HL, Khoury SJ

PLoS One. 2014; 9(7):e103716. Epub 2014 Jul 30. PMID: 25075741. Abstract

Does not appear to activate plasmacytoid dendritic cells in vitro

(209)

Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a cross-sectional observational study in patients with multiple sclerosis.

Kivisäkk P, Francois K, Mbianda J, Gandhi R, Weiner HL, Khoury SJ

PLoS One. 2014; 9(7):e103716. Epub 2014 Jul 30. PMID: 25075741. Abstract

May preferentially block activated plasmacytoid dendritic cell (PDC) migration (versus resting PDC migration) to lymphoid tissue, increasing the frequency of activated cells in circulation

(209)

Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a cross-sectional observational study in patients with multiple sclerosis.

Kivisäkk P, Francois K, Mbianda J, Gandhi R, Weiner HL, Khoury SJ

PLoS One. 2014; 9(7):e103716. Epub 2014 Jul 30. PMID: 25075741. Abstract

Associated with an increased proportion of CD19+ B cells in blood, but a decreased proportion in cerebrospinal fluid, in comparison to proportions in individuals with MS not treated with natalizumab

(230)

Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF.

Warnke C, Stettner M, Lehmensiek V, Dehmel T, Mausberg AK, von Geldern G, Gold R, Kümpfel T, Hohlfeld R, Mäurer M, et al.

Mult Scler. 2014 Nov 12. PMID: 25392339. Abstract

Reduces the CD4/CD8 ratio in cerebrospinal fluid, and reduces IgG and IgM levels and the IgG index, as shown in longitudinal studies

(230)

Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF.

Warnke C, Stettner M, Lehmensiek V, Dehmel T, Mausberg AK, von Geldern G, Gold R, Kümpfel T, Hohlfeld R, Mäurer M, et al.

Mult Scler. 2014 Nov 12. PMID: 25392339. Abstract

Reduces the intrathecally produced IgG fraction, as shown in longitudinal studies

(230)

Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF.

Warnke C, Stettner M, Lehmensiek V, Dehmel T, Mausberg AK, von Geldern G, Gold R, Kümpfel T, Hohlfeld R, Mäurer M, et al.

Mult Scler. 2014 Nov 12. PMID: 25392339. Abstract

Increases the number of circulating hematopoietic stem and progenitor cells, and these cells are primarily quiescent, indicating that they had recently mobilized from the bone marrow

(253)

Hematopoietic mobilization: Potential biomarker of response to natalizumab in multiple sclerosis.

Mattoscio M, Nicholas R, Sormani MP, Malik O, Lee JS, Waldman AD, Dazzi F, Muraro PA

Neurology. 2015 Mar 11. PMID: 25762712. Abstract

Increases the number of circulating hematopoietic stem and progenitor cells in some individuals, and this phenomenon is associated with clinical remission as well as an increased frequency of B cells and regulatory T cells

(253)

Hematopoietic mobilization: Potential biomarker of response to natalizumab in multiple sclerosis.

Mattoscio M, Nicholas R, Sormani MP, Malik O, Lee JS, Waldman AD, Dazzi F, Muraro PA

Neurology. 2015 Mar 11. PMID: 25762712. Abstract

Increases the mean total white cell, lymphocyte, and eosinophil counts in peripheral blood by month 1, and these counts then remain at these higher levels, as shown in an 18-month longitudinal study of 44 individuals with RRMS

(276)

Hematologic modifications in natalizumab-treated multiple sclerosis patients: An 18-month longitudinal study.

Bridel C, Beauverd Y, Samii K, Lalive PH

Neurol Neuroimmunol Neuroinflamm. 2015 Aug; 2(4):e123. Epub 2015 Jun 18. PMID: 26140281. Abstract

Progressively increases monocyte counts in peripheral blood, as shown in an 18-month longitudinal study of 44 individuals with RRMS

(276)

Hematologic modifications in natalizumab-treated multiple sclerosis patients: An 18-month longitudinal study.

Bridel C, Beauverd Y, Samii K, Lalive PH

Neurol Neuroimmunol Neuroinflamm. 2015 Aug; 2(4):e123. Epub 2015 Jun 18. PMID: 26140281. Abstract

Induces the appearance of erythroblasts and neurotrophil precursors in peripheral blood by month 1 in some individuals, as shown in an 18-month longitudinal study of 44 individuals with RRMS

(276)

Hematologic modifications in natalizumab-treated multiple sclerosis patients: An 18-month longitudinal study.

Bridel C, Beauverd Y, Samii K, Lalive PH

Neurol Neuroimmunol Neuroinflamm. 2015 Aug; 2(4):e123. Epub 2015 Jun 18. PMID: 26140281. Abstract

Does not affect mean erythrocyte, hemoglobin, hematocrit, thrombocyte, or neutrophil levels in peripheral blood, as shown in an 18-month longitudinal study of 44 individuals with RRMS

(276)

Hematologic modifications in natalizumab-treated multiple sclerosis patients: An 18-month longitudinal study.

Bridel C, Beauverd Y, Samii K, Lalive PH

Neurol Neuroimmunol Neuroinflamm. 2015 Aug; 2(4):e123. Epub 2015 Jun 18. PMID: 26140281. Abstract

Increases the relative percentage of certain minor lymphocyte subpopulations in whole blood, including early effector memory CD4+cells, central memory CD8+ T cells, recent thymic emigrants, and transitional B cells, as shown in a study of 11 individuals with RRMS treated with natalizumab and 23 untreated individuals with RRMS

(315)

Multiparametric flow cytometric analysis of whole blood reveals changes in minor lymphocyte subpopulations of multiple sclerosis patients.

Teniente-Serra A, Grau-López L, Mansilla JM, Fernández-Sanmartín M, Ester Condins A, Ramo-Tello C, Martínez-Cáceres E

Autoimmunity. 2016 Feb 1:1-10. PMID: 26829210. Abstract

Increases expression of surface integrin (CD49d and CD18) on CD14+CD16+ and CD14dimCD16+ peripheral monocyte subsets, as shown in a study of 11 individuals with RRMS followed for 1 year

(287)

Upregulation of integrin expression on monocytes in multiple sclerosis patients treated with natalizumab.

Dallari S, Franciotta D, Carluccio S, Signorini L, Gastaldi M, Colombo E, Bergamaschi R, Elia F, Villani S, Ferrante P, et al.

J Neuroimmunol. 2015 Oct 15; 287:76-9. Epub 2015 Aug 14. PMID: 26439965. Abstract

Decreases levels of neurofilament heavy and light chain (markers of axonal damage) in cerebrospinal fluid in RRMS patients, such that the effect is more pronounced for the light chain; in patients in remission, the effect was significant for the light but not heavy chain

(94)

Neurofilament light and heavy subunits compared as therapeutic biomarkers in multiple sclerosis.

Kuhle J, Malmeström C, Axelsson M, Plattner K, Yaldizli O, Derfuss T, Giovannoni G, Kappos L, Lycke J

Acta Neurol Scand. 2013 Jun 13. PMID: 23763388. Abstract

Associated with a decrease in levels of the glial marker YKL-40 in the cerebrospinal fluid (CSF) from individuals with MS; CSF YKL-40 levels are increased in MS relative to healthy controls

(158)

CSF levels of YKL-40 are increased in MS and replaces with immunosuppressive treatment.

Malmeström C, Axelsson M, Lycke J, Zetterberg H, Blennow K, Olsson B

J Neuroimmunol. 2014 Feb 13. PMID: 24582001. Abstract

Reduces levels of lipocalin-2, which is increased in progressive MS (and has been shown in inhibit remyelination in rat cultures), in the cerebrospinal fluid, as shown in a 60-week study of 17 individuals with this condition

(311)

Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination.

Al Nimer F, Elliott C, Bergman J, Khademi M, Dring AM, Aeinehband S, Bergenheim T, Romme Christensen J, Sellebjerg F, Svenningsson A, et al.

Neurol Neuroimmunol Neuroinflamm. 2016 Feb; 3(1):e191. Epub 2016 Jan 07. PMID: 26770997. Abstract

Associated with a reduction in serum levels of antibodies against neurofilament light protein, which are increased in individuals with RRMS and SPMS as compared with healthy controls

(150)

Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

Amor S, van der Star BJ, Bosca I, Raffel J, Gnanapavan S, Watchorn J, Kuhle J, Giovannoni G, Baker D, Malaspina A, et al.

Mult Scler. 2014 Feb 10. PMID: 24515731. Abstract

Reduces levels of oxidative damage biomarkers in individuals with RRMS

(108)

Effect of natalizumab on oxidative damage biomarkers in relapsing-remitting multiple sclerosis.

Tasset I, Bahamonde C, Agüera E, Conde C, Cruz AH, Pérez-Herrera A, Gascón F, Giraldo AI, Ruiz MC, Lillo R, et al.

Pharmacol Rep. 2013; 65(3):634-1. PMID: 23950585. Abstract

Associated with increased serum melatonin concentrations, increased antioxidants, and decreased oxidative stress biomarkers in individuals with RRMS

(157)

Elevated melatonin levels in natalizumab-treated female patients with relapsing-remitting multiple sclerosis: Relationship to oxidative stress.

Bahamonde C, Conde C, Agüera E, Lillo R, Luque E, Gascón F, Feijóo M, Cruz AH, Sánchez-López F, Túnez I

Eur J Pharmacol. 2014 Feb 25; 730C:26-30. PMID: 24582759. Abstract

Reduces concentrations of 24S-hydroxycholesterol in the cerebrospinal fluid, indicating reduced neurodegeneration, as shown in a 12-month study of 31 individuals with RRMS

(283)

Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis.

Novakova L, Axelsson M, Malmeström C, Zetterberg H, Björkhem I, Karrenbauer V D, Lycke J

J Neurol Sci. 2015 Aug 29. PMID: 26342940. Abstract

Reduces concentrations of 24S-hydroxycholesterol in the serum, and these serum concentrations correlate with scores on the Symbol Digit Modalities Test (a measure of cognition) before and after treatment, as shown in a 12-month study of 31 individuals with RRMS

(283)

Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis.

Novakova L, Axelsson M, Malmeström C, Zetterberg H, Björkhem I, Karrenbauer V D, Lycke J

J Neurol Sci. 2015 Aug 29. PMID: 26342940. Abstract

Reduces concentrations of 27-hydroxycholesterol in the cerebrospinal fluid, indicating improved blood-brain barrier integrity, as shown in a 12-month study of 31 individuals with RRMS

(283)

Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis.

Novakova L, Axelsson M, Malmeström C, Zetterberg H, Björkhem I, Karrenbauer V D, Lycke J

J Neurol Sci. 2015 Aug 29. PMID: 26342940. Abstract

Reduces plasma levels of osteopontin (a protein with roles in inflammation and immunity), which are increased in RRMS and SPMS

(111)

Evaluation of circulating osteopontin levels in an unselected cohort of patients with multiple sclerosis: relevance for biomarker development.

Kivisäkk P, Healy BC, Francois K, Gandhi R, Gholipour T, Egorova S, Sevdalinova V, Quintana F, Chitnis T, Weiner HL, et al.

Mult Scler. 2013 Sep 4. PMID: 24005026. Abstract

Effectiveness is not increased in patients carrying the CCR5 delta32 deletion allele versus those who do not; this idea was tested because CCR5 (a chemokine receptor) might play a role in recruiting T cells to the central nervous system in MS

(87)

The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis.

Møller M, Søndergaard HB, Koch-Henriksen N, Sorensen PS, Sellebjerg F, Oturai AB

Acta Neurol Scand. 2013 May 14. PMID: 23668375. Abstract

In individuals switching from natalizumab to fingolimod, a low saturation (<30%) of natalizumab on the surface of CD8+ and CD4+ T cells before beginning fingolimod is associated with disease activity during a 6-month followup, whereas higher levels (66 to 70%) are associated with absence of disease, based on a pilot study of 5 individuals with MS

(114)

Natalizumab saturation: biomarker for individual treatment holiday after natalizumab withdrawal?

Wipfler P, Harrer A, Pilz G, Oppermann K, Afazel S, Haschke-Becher E, Sellner J, Trinka E, Kraus J

Acta Neurol Scand. 2013 Aug 30. PMID: 24032536. Abstract

Natalizumab antigen-binding fragment binds outside the ligand-binding groove for vascular cell adhesion molecule domain 1 on the α4 integrin subunit, as shown by X-ray crystallography

(117)

How Natalizumab Binds and Antagonizes α4 Integrins.

Yu Y, Schürpf T, Springer TA

J Biol Chem. 2013 Sep 18. PMID: 24047894. Abstract

Non-competitively inhibits binding of vascular cell adhesion molecule to the α4 integrin subunit, as shown by radioligand binding assays

(117)

How Natalizumab Binds and Antagonizes α4 Integrins.

Yu Y, Schürpf T, Springer TA

J Biol Chem. 2013 Sep 18. PMID: 24047894. Abstract

Upon binding to integrin, may drive the vascular cell adhesion molecule domain 2 into a non-preferred position, as shown by X-ray crystallography and binding assays

(117)

How Natalizumab Binds and Antagonizes α4 Integrins.

Yu Y, Schürpf T, Springer TA

J Biol Chem. 2013 Sep 18. PMID: 24047894. Abstract

During the first year of treatment, decreases the extent and severity of damage to white matter, as shown in a diffusion tensor imaging study of 22 individuals with RRMS

(320)

White Matter Diffusion Changes during the First Year of Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis.

Wiebenga OT, Schoonheim MM, Hulst HE, Nagtegaal GJA, Strijbis EMM, Steenwijk MD, Polman CH, Pouwels PJW, Barkhof F, Geurts JJG

AJNR Am J Neuroradiol. 2016 Mar 10. PMID: 26965463. Abstract

Improves performance in walking-related parameters when individuals are asked to walk and perform a cognitive task at the same time, but does not improve such parameters when walking is the only task being performed, based on a study of 9 individuals with MS over 1 year

(148)

Dual-Task Assessment in Natalizumab-Treated Multiple Sclerosis Patients.

Allali G, Laidet M, Assal F, Chofflon M, Armand S, Lalive PH

Eur Neurol. 2014 Feb 1; 71(5-6):149-153. Epub 2014 Feb 01. PMID: 24503719. Abstract

Treatment results in sustained disability improvement in ~30% of individuals with MS, as well as a reduction in the MRI lesion burden; the improvement in disability is associated with shrinkage of the T1 lesion volume

(177)

Sustained disability improvement is associated with T1 lesion volume shrinkage in natalizumab-treated patients with multiple sclerosis.

Prosperini L, De Angelis F, De Angelis R, Fanelli F, Pozzilli C

J Neurol Neurosurg Psychiatry. 2014 Apr 30. PMID: 24790213. Abstract

Associated with a relative reduction of 42.8%% in the risk of ≥1 relapses during 2 years of treatment and is more cost effective than interferon beta-1a (Avonex or Rebif), interferon beta-1b (Betaferon), or glatiramer acetate, according to a pharmacoeconomic analysis that used pre-existing data

(90)

Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.

Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G

Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract

and costs of treatment in the Russian healthcare system

(199)

[Pharmacoeconomic analysis of the efficacy of natalizumab in relapsing-remitting multiple sclerosis].

Zh Nevrol Psikhiatr Im S S Korsakova. 2014; 114(5):65-9. PMID: 24988963. Abstract

Effectiveness (measured in terms of a lack of relapses and disease progression) correlates with a decrease in the titer of IgG antibodies against human herpes virus 6A/B, whereas an increase predicts relapse, as shown in a 2-year longitudinal study

(210)

Anti-Human Herpesvirus 6A/B IgG Correlates with Relapses and Progression in Multiple Sclerosis.

Ortega-Madueño I, Garcia-Montojo M, Dominguez-Mozo M I, Garcia-Martinez A, Arias-Leal A M, Casanova I, Arroyo R, Alvarez-Lafuente R

PLoS One. 2014; 9(8):e104836. Epub 2014 Aug 11. PMID: 25110949. Abstract

Early treatment is associated with an increase in the absolute concentration of N-acetylaspartate (a marker of neuronal integrity) and other brain metabolites in lesional white matter (where concentrations are reduced relative to normal white matter), potentially indicating increased axonal metabolism, as shown in a longitudinal study of individuals with RRMS

(251)

Enhanced Axonal Metabolism during Early Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis.

Wiebenga OT, Klauser AM, Schoonheim MM, Nagtegaal GJA, Steenwijk MD, van Rossum J, Polman CH, Barkhof F, Pouwels PJW, Geurts JJG

AJNR Am J Neuroradiol. 2015 Mar 5. PMID: 25742985. Abstract

Induces lymphocytosis, and people who exhibit lower-than-expected lymphocytosis may have a higher risk of relapse, indicating that such natalizumab-induced lymphocytosis may be useful as a biomarker of therapeutic efficacy, as shown in a study of 50 individuals with RRMS or progressive-relapsing MS who had been given ≥16 natalizumab infusions

(292)

Lymphocytosis as a response biomarker of natalizumab therapeutic efficacy in multiple sclerosis.

Signoriello E, Lanzillo R, Brescia Morra V, Di Iorio G, Fratta M, Carotenuto A, Lus G

Mult Scler. 2015 Oct 9. PMID: 26453682. Abstract

Appears to reduce the high risk of post-partum relapse when restarted soon after delivery (on average, 7.8 days later) in women who had stopped therapy during pregnancy, as shown in a retrospective analysis of 6 women with very active MS in whom disease activity disappeared in all but 1 of them after such early redosing

(221)

Natalizumab for the prevention of post-partum relapses in women with multiple sclerosis.

Vukusic S, Durand-Dubief F, Benoit A, Marignier R, Frangoulis B, Confavreux C

Mult Scler. 2014 Oct 10. PMID: 25305253. Abstract

Does not affect the response to immunization with either a recall antigen (tetanus toxoid) or a neoantigen (keyhold limpet hemocyanin) in a clinically relevant manner, on the basis of a study of 60 individuals with RRMS, 30 who were natalizumab-naïve and 30 who had received 6 months of natalizumab treatment

(174)

Natalizumab treatment shows no clinically meaningful effects on immunization responses in patients with relapsing-remitting multiple sclerosis.

Kaufman M, Pardo G, Rossman H, Sweetser MT, Forrestal F, Duda P

J Neurol Sci. 2014 Mar 26. PMID: 24731783. Abstract

Does not impair the function of CD4+ CD8+ T cells, which are present in the circulation at similar frequencies in individuals with and without MS; the cells are also present in the cerebrospinal fluid, but not in inflammed MS lesions

(175)

Analysis of CD4+CD8+ double positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions.

Waschbisch A, Sammet L, Schröder S, Lee D-H, Barrantes-Freer A, Stadelmann C, Linker RA

Clin Exp Immunol. 2014 Apr 14. PMID: 24730443. Abstract

Treatment can be associated with a transient reactivation of Epstein-Barr virus (EBV), but EBV-specific antibody levels do not appear to be useful as a biomarker for therapeutic natalizumab response, as shown in a 21-month study of 20 individuals with MS

(270)

Epstein-Barr Virus Specific Antibody Response in Multiple Sclerosis Patients during 21 Months of Natalizumab Treatment.

Castellazzi M, Delbue S, Elia F, Gastaldi M, Franciotta D, Rizzo R, Bellini T, Bergamaschi R, Granieri E, Fainardi E

Dis Markers. 2015; 2015:901312. Epub 2015 May 26. PMID: 26101453. Abstract

Does not affect the percentage of circulating 6-sulfo LacNAc(+) dendritic cells, proinflammatory cells that are present in demyelinated brain lesions and are often present in cerebrospinal fluid in individuals with MS

(223)

Accumulation and therapeutic modulation of 6-sulfo LacNAc(+) dendritic cells in multiple sclerosis.

Thomas K, Dietze K, Wehner R, Metz I, Tumani H, Schultheiß T, Günther C, Schäkel K, Reichmann H, Brück W, et al.

Neurol Neuroimmunol Neuroinflamm. 2014 Oct; 1(3):e33. Epub 2014 Sep 18. PMID: 25340085. Abstract

Does not affect human melanoma cell proliferation in vitro, but does reduce migration and invasion of such cells in vitro

(226)

Risk for nevus transformation and melanoma proliferation and invasion during natalizumab treatment: four years of dermoscopic follow-up with immunohistological studies and proliferation and invasion assays.

Pharaon M, Tichet M, Lebrun-Frénay C, Tartare-Deckert S, Passeron T

JAMA Dermatol. 2014 Aug; 150(8):901-3. PMID: 24919481. Abstract

Animal:

Blocks the firm adhesion (rather than the initial contact) of human T cells to the blood brain barrier in experimental autoimmune encephalomyelitis

(17)

Cutting edge: Natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis.

Coisne C, Mao W, Engelhardt B

J Immunol. 2009 May 15; 182(10):5909-13. PMID: 19414741. Abstract

Reduces leukocyte migration into the brain parenchyma in experimental autoimmune encephalomyelitis models

(14)

Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin.

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Antibodies against α4β1 integrin (i.e., not natalizumab per se) inhibit binding of lymphocytes and monocytes to inflammed experimental autoimmune encephalomyelitis brain vessels

(6)

Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N

Nature. 1992 Mar 5; 356(6364):63-6. PMID: 1538783. Abstract

Antibodies against α4β1 integrin (i.e., not natalizumab per se) prevent the development of experimental autoimmune encephalomyelitis

(6)

Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin.

Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N

Nature. 1992 Mar 5; 356(6364):63-6. PMID: 1538783. Abstract

Reduces levels of lipocalin 2 in the cerebrospinal fluid (CSF) and astrocytes in a mouse experimental autoimmune encephalomyelitis model; lipocalin 2 expression is upregulated in CSF in this model and in MS patients

(32)

Lipocalin 2 is present in the EAE brain and is modulated by natalizumab.

Marques F, Mesquita SD, Sousa JC, Coppola G, Gao F, Geschwind DH, Columba-Cabezas S, Aloisi F, Degn M, Cerqueira JJ, et al.

Front Cell Neurosci. 2012; 6:33. Epub 2012 Aug 09. PMID: 22907989. Abstract

Antibodies against α4 integrin (i.e., not natalizumab per se) suppress experimental autoimmune encephalomyelitis (EAE) in wild-type mice, whereas they do not suppress EAE in mice deficient for epithelial V-like antigen (which develop more severe EAE than wild-type mice), suggesting that EVA expression is needed for the best therapeutic response to these antibodies

(109)

Epithelial v-like antigen mediates efficacy of anti-alpha4 integrin treatment in a mouse model of multiple sclerosis.

Wright E, Rahgozar K, Hallworth N, Lanker S, Carrithers MD

PLoS One. 2013; 8(8):e70954. Epub 2013 Aug 08. PMID: 23951051. Abstract

Antibodies against α4 integrin (i.e., not natalizumab per se) reduce the frequency of mature B lymphocytes (as well as T lymphocytes) in the central nervous system in wild-type mice with experimental autoimmune encephalomyelitis (EAE), but not in EAE mice deficient for epithelial V-like antigen

(109)

Epithelial v-like antigen mediates efficacy of anti-alpha4 integrin treatment in a mouse model of multiple sclerosis.

Wright E, Rahgozar K, Hallworth N, Lanker S, Carrithers MD

PLoS One. 2013; 8(8):e70954. Epub 2013 Aug 08. PMID: 23951051. Abstract

Antibodies against α4 integrin reduce expression of chemokine SDF-1/CXCL12 and its receptor CXCR4 in an experimental autoimmune encephalomyelitis (EAE) model; both the chemokine and its receptor are upregulated in EAE

(147)

Integrin/Chemokine Receptor Interactions in the Pathogenesis of Experimental Autoimmune Encephalomyelitis.

Banisadr G, Schwartz SR, Podojil JR, Piccinini LA, Lanker S, Miller SD, Miller RJ

J Neuroimmune Pharmacol. 2014 Jan 30. Epub 2014 Jan 30. PMID: 24477403. Abstract

Early treatment reduces the severity of a progressive form of experimental autoimmune encephalomyelitis in mice, whereas later treatment is less effective

(191)

Early Treatment with Anti-VLA-4 mAb Can Prevent the Infiltration and/or Development of Pathogenic CD11b+CD4+ T Cells in the CNS during Progressive EAE.

Mindur JE, Ito N, Dhib-Jalbut S, Ito K

PLoS One. 2014; 9(6):e99068. Epub 2014 Jun 04. PMID: 24896098. Abstract

Early treatment reduces the accumulation of CD11b+CD4+ T cells producing granulocyte macrophage colony-stimulating factor in the central nervous system in a progressive experimental autoimmune encephalomyelitis mouse model

(191)

Early Treatment with Anti-VLA-4 mAb Can Prevent the Infiltration and/or Development of Pathogenic CD11b+CD4+ T Cells in the CNS during Progressive EAE.

Mindur JE, Ito N, Dhib-Jalbut S, Ito K

PLoS One. 2014; 9(6):e99068. Epub 2014 Jun 04. PMID: 24896098. Abstract

Early treatment protects neurons against inflammation-driven neurodegeneration in a progressive experimental autoimmune encephalomyelitis mouse model

(191)

Early Treatment with Anti-VLA-4 mAb Can Prevent the Infiltration and/or Development of Pathogenic CD11b+CD4+ T Cells in the CNS during Progressive EAE.

Mindur JE, Ito N, Dhib-Jalbut S, Ito K

PLoS One. 2014; 9(6):e99068. Epub 2014 Jun 04. PMID: 24896098. Abstract

Regulatory and Commercial Status

Status for MS:

Approved in the US for treating relapsing forms of MS (November, 2004)

(4)

New approaches in the management of multiple sclerosis.

Barten LJ, Allington DR, Procacci KA, Rivey MP

Drug Des Devel Ther. 2010; 4:343-66. Epub 2010 Nov 24. PMID: 21151622. Abstract

(15)

Tysabri

Biogen Idec, 2011

Accessed on 21 Nov 2011 from http://www.biogenidec.com/therapies_tysabri.aspx?ID=5589.

(263)

Medscape, 8 May 2015

Accessed on 12 May 2015 from http://www.medscape.com/viewarticle/844431.

Approved in the EU for treating highly active RRMS (June, 2006)

(263)

New approaches in the management of multiple sclerosis.

Medscape, 8 May 2015

Accessed on 12 May 2015 from http://www.medscape.com/viewarticle/844431.

Highest status achieved (for any condition):

Approved

(4)

Barten LJ, Allington DR, Procacci KA, Rivey MP

Drug Des Devel Ther. 2010; 4:343-66. Epub 2010 Nov 24. PMID: 21151622. Abstract

Other uses:

Effectively used to treat a case of Balò's concentric sclerosis, which is considered a variant of MS

(274)

Balò's concentric sclerosis: still to be considered as a variant of multiple sclerosis?

Pietroboni AM, Arighi A, De Riz MA, Ghezzi L, Calvi A, Avignone S, Scola E, Galimberti D, Triulzi F, Scarpini E

Neurol Sci. 2015 Jun 25. Epub 2015 Jun 25. PMID: 26109007. Abstract

Approved for treating moderate to severe Crohn's disease in patients who do not respond to or are intolerant of other treatments

(8)

An evidence-based review of natalizumab therapy in the management of Crohn's disease.

Edula R G, Picco MF

Ther Clin Risk Manag. 2009; 5:935-42. Epub 2009 Nov 29. PMID: 20011247. Abstract

Tested in a Phase II trial for treating rheumatoid arthritis, but study was terminated because effect was not sufficient to support further development

(10)

Natalizumab in the treatment of rheumatoid arthritis in subjects receiving methotrexate

ClinicalTrials.gov, 1 Jun 2009

Accessed on 21 Nov 2011 from http://clinicaltrials.gov/show/NCT00083759.

Was unsuccessful for treating neuromyelitis optica (which later responded to immunosuppressive therapy) in one case

(187)

Neuromyelitis optica presenting with relapses under treatment with natalizumab: a case report.

Lee D-H, Laemmer AB, Waschbisch A, Struffert T, Maihöfner C, Schwab S, Linker R A

J Med Case Rep. 2014; 8(1):155. Epub 2014 May 19. PMID: 24886528. Abstract

Administration:

300 mg via intravenous infusion every four weeks (this information was provided by the manufacturer)

(14)

Extending Treatment Up To Eight Weeks With Infusion Medication Shown Safe and Effective in Patients with Multiple Sclerosis

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

(259)

NYU Langone Medical Center, 22 Apr 2015

Accessed on 28 Apr 2015 from http://nyulangone.org/press-releases/extending-treatment-up-to-eight-weeks-with-infusion-medication-shown-safe-and-effective-in-patients-with-multiple-sclerosis.

; further analysis indicated that an 8-week dosing interval might reduce relapse rates and MRI lesions as compared with the 4-week interval (meeting report, October 2015)

(290)

New Data Show Longer Tysabri Dosing Interval in MS Is Feasible

Gever J, MedPage Today, 7 Oct 2015

Accessed on 13 Oct 2015 from http://www.medpagetoday.com/clinical-context/MultipleSclerosis/53960.

Review to assess whether the current approach for managing the risk of progressive multifocal leukoencephalopathy needs to be revised has been requested by the European Commission (May 2015)

(263)

New EMA Advice to Reduce PML Risk With Natalizumab (Tysabri) in MS

Medscape, 8 May 2015

Accessed on 12 May 2015 from http://www.medscape.com/viewarticle/844431.

; new guidelines have been issued by the European Medicines Agency (February 2016)

(318)

Jeffrey S, Medscape, 12 Feb 2016

Accessed on 16 Feb 2016 from http://www.medscape.com/viewarticle/858883.

Negative effects:

Allergic reactions

(3)

Biogen Idec and Elan Pharmaceuticals

Accessed on 21 Nov 2011 from http://www.tysabri.com/tysbProject/tysb.portal/_baseurl/threeColLayout/SCSRepository/en_US/tysb/home/index.xml?utm_campaign=Branded&utm_source=google&utm_medium=cpc&utm_content=Tysabri&utm_term=Natalizumab.

Anaphylaxis

(3)

Severe anemia in a patient with multiple sclerosis treated with natalizumab.

Biogen Idec and Elan Pharmaceuticals

Associated with anaphylactoid reactions in some individuals; specific human leukocyte antigen (HLA) alleles (HLA-DRB1*13 and HLA-DRB1*14) were present at increased frequency in a group of 54 such individuals, whereas the HLA-DRB1*15 allele was present at increased frequency in a group of 65 who lacked such reactions, suggesting that HLA-DRB1 genotyping before natalizumab therapy could be useful

(238)

de la Hera B, Urcelay E, Brassat D, Chan A, Vidal-Jordana A, Salmen A, Villar L M, Alvarez-Cermeño J C, Izquierdo G, Fernández O, et al.

Neurol Neuroimmunol Neuroinflamm. 2014 Dec; 1(4):e47. Epub 2014 Dec 11. PMID: 25520955. Abstract

Associated with severe anemia in one individual with MS

(196)

Simone A M, Ferraro D, Vitetta F, Marasca R, Bonacorsi G, Pinelli G, Federzoni L, Nichelli P F, Sola P

Neurology. 2014 Jun 18. PMID: 24944259. Abstract

Severe anemia has been reported in one individual with MS treated with natalizumab

(247)

Severe anemia in a patient with multiple sclerosis treated with natalizumab.

Seibert JB, Alvarez E

Neurology. 2015 Feb 24; 84(8):861. PMID: 25713115. Abstract

Arm and leg pain

(3)

Biogen Idec and Elan Pharmaceuticals

Breathing problems

(3)

JCV granule cell neuronopathy and GCN-IRIS under natalizumab treatment.

Biogen Idec and Elan Pharmaceuticals

Cerebellar granule cell neuronopathy, a central nervous system disease associated with JC virus, has been observed in one patient

(100)

Schippling S, Kempf C, Büchele F, Jelcic I, Bozinov O, Bont A, Linnebank M, Sospedra M, Weller M, Budka H, et al.

Ann Neurol. 2013 Jul 19. PMID: 23868420. Abstract

Associated with granule cell neuronopathy (GCN) in a second individual, who carried JC virus containing GCN-type mutations in the VP1 capsid gene

(207)

JCV GCN in a natalizumab-treated MS patient is associated with mutations of the VP1 capsid gene.

Agnihotri SP, Dang X, Carter JL, Fife TD, Bord E, Batson S, Koralnik IJ

Neurology. 2014 Jul 18. PMID: 25037207. Abstract

Associated with human papilloma virus-positive cervical dysplasia in 4 individuals with MS

(202)

Cervical dysplasia associated with the use of natalizumab.

Rolfes L, Lokhorst B, Samijn J, van Puijenbroek E

Neth J Med. 2013 Nov; 71(9):494-5. PMID: 24218428. Abstract

Chest pain

(3)

Biogen Idec and Elan Pharmaceuticals

Chills

(3)

Cryptococcal meningitis in a multiple sclerosis patient taking natalizumab.

Biogen Idec and Elan Pharmaceuticals

Cryptococcal meningitis developed in one individual with MS who was being treated with natalizumab

(169)

Valenzuela R M, Pula JH, Garwacki D, Cotter J, Kattah JC

J Neurol Sci. 2014 Mar 11. PMID: 24680560. Abstract

Depression

(3)

Acquired perforating dermatosis associated with natalizumab.

Biogen Idec and Elan Pharmaceuticals

Associated with acquired perforating dermatosis

(98)

Piqué-Duran E, Eguía P, García-Vázquez O

J Am Acad Dermatol. 2013 Jun; 68(6):e185-7. PMID: 23680214. Abstract

Diarrhea

(3)

Biogen Idec and Elan Pharmaceuticals

Dizziness

(3)

Eosinophilic Fasciitis Occurring under Treatment with Natalizumab for Multiple Sclerosis.

Biogen Idec and Elan Pharmaceuticals

Associated with eosinophilic fasciitis (a sclerosing syndrome) in one individual with MS

(138)

Bujold J, Boivin C, Amin M, Bouchard J-P, Soucy J

J Cutan Med Surg. 2014; 18:69-71. PMID: 24377479. Abstract

Causes erythroblastemia (the presence of erythroblasts in the peripheral blood, a condition linked with serious disorders) in most treated individuals

(149)

The anti-VLA-4 antibody natalizumab induces erythroblastaemia in the majority of the treated patients with multiple sclerosis.

Robier C, Amouzadeh-Ghadikolai O, Bregant C, Diez J, Melinz K, Neubauer M, Quasthoff S

Mult Scler. 2014 Feb 3. PMID: 24493472. Abstract

Fatigue

(3)

Biogen Idec and Elan Pharmaceuticals

Flushing skin

(3)

Concomitant granule cell neuronopathy in patients with natalizumab-associated PML.

Biogen Idec and Elan Pharmaceuticals

Three individuals with apparent granule cell neuronopathy (JC virus infection of cerebellar granule cell neurons, characterized by cerebellar atrophy) were identified among 44 individuals with natalizumab-associated progressive multifocal leukoencephalopathy (PML); no cases were found in a control group of 25 natalizumab-treated individuals without PML

(312)

Wijburg MT, Siepman D, van Eijk JJJ, Killestein J, Wattjes MP

J Neurol. 2016 Jan 25. PMID: 26810721. Abstract

Headache

(3)

Natalizumab-induced autoimmune hepatitis in a patient with multiple sclerosis.

Biogen Idec and Elan Pharmaceuticals

Natalizumab-induced autoimmune hepatitis has been observed in one MS patient

(44)

Martínez-Lapiscina E, Lacruz F, Bolado-Concejo F, Rodríguez-Pérez I, Ayuso T, Garaigorta M, Urman J

Mult Scler. 2012 Oct 15. PMID: 23069876. Abstract

Herpes zoster has been reported in three cases

(72)

Report of Three Cases of Herpes Zoster During Treatment with Natalizumab.

Fragoso Y D, Brooks J B B, Gomes S, de Oliveira F T M, da Gama P D

CNS Neurosci Ther. 2013 Feb 18. PMID: 23419219. Abstract

; central nervous system herpesvirus infection has been confirmed in 20 cases

(91)

Central Nervous System Herpes Simplex and Varicella-Zoster Virus Infections in Natalizumab-Treated Patients.

Fine AJ, Sorbello A, Kortepeter C, Scarazzini L

Clin Infect Dis. 2013 May 31. PMID: 23728144. Abstract

Varicella-zoster virus myelitis has been reported in one patient

(85)

Varicella-zoster virus acute myelitis in a patient with MS treated with natalizumab.

Yeung J, Cauquil C, Saliou G, Nasser G, Rostomashvili S, Adams D, Théaudin M

Neurology. 2013 Apr 24. PMID: 23616161. Abstract

Hives

(3)

Immune reconstitution inflammatory syndrome mimicking progressive multifocal leucoencephalopathy in a multiple sclerosis patient treated with natalizumab: a case report and review of the literature.

Biogen Idec and Elan Pharmaceuticals

Immune reconstitution inflammatory syndrome, which mimicked progressive multifocal leucoencephalopathy, has been reported in one individual with RRMS treated with natalizumab

(228)

Evangelopoulos M-E, Koutoulidis V, Kilidireas K, Evangelopoulos D-S, Nakas G, Andreadou E, Moulopoulos L-A

J Clin Med Res. 2015 Jan; 7(1):65-8. Epub 2014 Oct 16. PMID: 25368707. Abstract

Acute immune reconstitution inflammatory syndrome-associated cryptococcal meningoencephalitis has been reported in an individual with MS treated with natalizumab

(322)

Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab.

Gundacker ND, Jordan SJ, Jones BA, Drwiega JC, Pappas PG

Open Forum Infect Dis. 2016 Jan; 3(1):ofw038. Epub 2016 Feb 17. PMID: 27006962. Abstract

Infections

(3)

Biogen Idec and Elan Pharmaceuticals

Itching

(3)

Biogen Idec and Elan Pharmaceuticals

Joint pain

(3)

Biogen Idec and Elan Pharmaceuticals

Liver damage

(3)

Natalizumab-induced hepatic injury: A case report and review of literature.

Biogen Idec and Elan Pharmaceuticals

Severe natalizumab-associated liver injury has been reported in 12 individuals and almost 30 cases of natalizumab-associated liver failure have been listed in the postmarketing US Food and Drug Administration's adverse event reporting system (November 2015)

(300)

Antezana A, Sigal S, Herbert J, Kister I

Mult Scler Relat Disord. 2015 Nov; 4(6):495-8. Epub 2015 Sep 03. PMID: 26590653. Abstract

Low blood pressure

(3)

Asymptomatic lung disease caused by Mycobacterium kansasii as an opportunistic infection in a patient treated with natalizumab for relapsing-remitting multiple sclerosis.

Biogen Idec and Elan Pharmaceuticals

Asymptomatic lung disease resulting from an opportunistic infection of Mycobacterium kansasii has been observed in an individual with RRMS treated with natalizumab

(107)

Hradilek P, Zeman D, Tudik I, Zapletalova O, Ulmann V

Mult Scler. 2013 Aug 19. PMID: 23959714. Abstract

Possibly causally associated with primary central nervous system lymphoma in one individual

(139)

Central nervous system lymphoma associated with natalizumab.

Na A, Hall N, Kavar B, King J

J Clin Neurosci. 2013 Nov 9. PMID: 24373819. Abstract

Possibly causally associated with non-Hodgkin lymphoma of the stomach in one individual with RRMS

(277)

Non-Hodgkin Lymphoma of the Stomach in a Patient Treated with Natalizumab.

Law JY, Kim DW, Sturgis A, Naina HV

Clin Med Insights Oncol. 2015; 9:61-3. Epub 2015 Jul 01. PMID: 26157340. Abstract

Associated with melanoma in two individuals

(162)

Melanoma complicating treatment with natalizumab for multiple sclerosis.

Mullen JT, Vartanian TK, Atkins MB

N Engl J Med. 2008 Feb 7; 358(6):647-8. PMID: 18256405. Abstract

Likely associated with toxic acute myocardial damage in an individual with RRMS

(306)

Natalizumab treatment for multiple sclerosis inducing a toxic acute myocardial damage. Is there any relationship?

Fama' F, Dattola V, Cicciu' M, Buccafusca M, Russo M, Lo Presti D, Dattilo G, Di Bella G

Int J Cardiol. 2016 Mar 1; 206:127-8. Epub 2016 Jan 08. PMID: 26788687. Abstract

Nausea

(3)

Neuroborreliosis during natalizumab treatment in multiple sclerosis.

Biogen Idec and Elan Pharmaceuticals

Acute neuroborreliosis occurred in one individual with RRMS during long-term treatment with natalizumab

(103)

Thomas K, Schultheiss T, Ziemssen T

Neurology. 2013 Jul 26. PMID: 23892705. Abstract

Fatal neuroinflammation occurred in one patient with anti-natalizumab antibodies

(66)

Fatal Neuroinflammation in a Case of Multiple Sclerosis with Anti-Natalizumab Antibodies.

Svenningsson A, Dring AM, Fogdell-Hahn A, Jones I, Engdahl E, Lundkvist M, Brännström T, Gilthorpe JD

Neurology. 2013 Feb 6. PMID: 23390173. Abstract

Can potentially exacerbate neuromyelitis optica (NMO); a single dose was associated with a catastrophic brain relapse in an individual with NMO who was seronegative for aquaporin-4 antibodies

(237)

Catastrophic brain relapse in seronegative NMO after a single dose of natalizumab.

Kitley J, Evangelou N, Küker W, Jacob A, Leite IM, Palace J

J Neurol Sci. 2014 Feb 4. PMID: 24576801. Abstract

Progressive multifocal leucoencaphalopathy

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

As of 2013, has been associated with 399 cases of progressive multifocal leukoencephalopathy throughout the world

(124)

Natalizumab-associated progressive multifocal leukoencephalopathy in a patient with multiple sclerosis: a postmortem study.

Wüthrich C, Popescu B GF, Gheuens S, Marvi M, Ziman R, Denq S P, Tham M, Norton E, Parisi JE, Dang X, et al.

J Neuropathol Exp Neurol. 2013 Nov; 72(11):1043-51. PMID: 24128680. Abstract

Changes in T cell responses that are specific to JC virus [which causes progressive multifocal leukoencephalopathy (PML) only with immunodeficiency or immunosuppression] may be a risk factor for PML

(51)

Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy.

Perkins MR, Ryschkewitsch C, Liebner JC, Monaco M CG, Himelfarb D, Ireland S, Roque A, Edward HL, Jensen PN, Remington G, et al.

PLoS Pathog. 2012 Nov; 8(11):e1003014. Epub 2012 Nov 08. PMID: 23144619. Abstract

Progressive multifocal leukoencephalopathy has been detected in a patient in which four samples of cerebrospinal fluid were negative for JC virus DNA, as assayed by PCR, but a brain biopsy eventually was shown to be positive, as assayed by immunohistochemistry

(53)

A case of natalizumab-associated progressive multifocal leukoencephalopathy with repeated negative CSF JC virus testing.

Mazda ME, Brosch JR, Wiens AL, Bonnin J, Kamer AP, Mattson DH, Snook RJ

Int J Neurosci. 2012 Dec 20. PMID: 23252596. Abstract

Presumptive progressive multifocal leukoencephalopathy has been detected in an RRMS patient 14 weeks after the discontinuation of natalizumab, after 36 months of therapy; cerebrospinal fluid was negative for JC virus

(60)

Presumptive Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis after Natalizumab Therapy.

Eisele P, Szabo K, Hornberger E, Griebe M, Hennerici MG, Kieseier BC, Gass A

J Neuroimaging. 2013 Jan 16. PMID: 23323645. Abstract

Natalizumab-associated progressive multifocal leukoencephalopathy, detected presymptomatically with MRI in an MS patient, was effectively treated with plasma exchange and steroid treatment

(71)

Presymptomatic diagnosis with MRI and adequate treatment ameliorate the outcome after natalizumab-associated progressive multifocal leukoencephalopathy.

Lindå H, von Heijne A

Front Neurol. 2013; 4:11. Epub 2013 Feb 18. PMID: 23423248. Abstract

Increases the risk of progressive multifocal leukoencephalopathy (PML), but early detection of this condition (by brain scans and spinal fluid tests, before symptoms occur) may be associated with improved survival, as shown in an industry-sponsored study of 319 natalizumab-treated MS patients diagnosed with PML

(73)

Early detection of MS treatment complication may improve survival

Market Watch, The Wall Street Journal, 10 Mar 2013

Accessed on 13 Mar 2013 from http://www.marketwatch.com/story/early-detection-of-ms-treatment-complication-may-improve-survival-2013-03-10.

During prolonged natalizumab therapy, some MS patients display signs of replication of JC virus (which causes progressive multifocal leukoencephalopathy)

(80)

Immunological Hallmarks of JC Virus Replication in Multiple Sclerosis Patients on Long-Term Natalizumab.

Hendel-Chavez H, de Goër de Herve M-G, Giannesini C, Mazet A-A, Papeix C, Louapre C, Chardain A, Boutarfa N, Théaudin M, Adams D, et al.

J Virol. 2013 Mar 20. PMID: 23514886. Abstract

Rate of JC virus seroconversion (from negative to positive) in individuals with MS receiving natalizumab has been quantified in a French cohort

(113)

JC-virus seroconversion in multiple sclerosis patients receiving natalizumab.

Outteryck O, Zéphir H, Salleron J, Ongagna J-C, Etxeberria A, Collongues N, Lacour A, Fleury M-C, Blanc F, Giroux M, et al.

Mult Scler. 2013 Sep 26. PMID: 24072722. Abstract

Risk for natalizumab-associated progressive multifocal leukoencephalopathy is associated with low body weight, potentially because higher drug concentrations occur in patients with lower weight

(82)

Low body weight linked to PML risk with natalizumab in MS

Medscape Today, 3 Apr 2013

Accessed on 8 Apr 2013 from http://www.medscape.com/viewarticle/781879.

Risk for natalizumab-associated progressive multifocal leukoencephalopathy (PML) is considered relatively low in patients testing negative for anti-JC virus antibodies, but about a third of MS patients (in a group of 49) who tested negative for such antibodies had active viremia, indicating they might in fact be at high risk for PML

(88)

Tysabri screening test may be unreliable

Gever J, Medpage Today, 5 Jun 2013

Accessed on 7 Jun 2013 from http://www.medpagetoday.com/Neurology/MultipleSclerosis/39649.

(89)

JC viremia in natalizumab-treated patients with multiple sclerosis.

Major EO, Frohman E, Douek D

N Engl J Med. 2013 Jun 6; 368(23):2240-1. PMID: 23738566. Abstract

Risk for natalizumab-associated progressive multifocal leukoencephalopathy (PML) is higher in patients who exhibit an increased anti-JC virus antibody index more than 6 months before the PML diagnosis (relative to those without a PML diagnosis)

(96)

JCV test stratifies PML risk in antibody-positive MS

Keller DM, Medscape Today, 14 Jun 2013

Accessed on 24 Jun 2013 from http://www.medscape.com/viewarticle/806294.

Risk for natalizumab-associated progressive multifocal leukoencephalopathy may be further defined among individuals positive for anti-JC virus antibodies by the serum or plasma level of such antibodies (measured as an index); this idea would apply to individuals without prior immunosuppressant use

(220)

Anti-JCV antibody levels in serum or plasma further define risk of natalizumab-associated PML.

Plavina T, Subramanyam M, Bloomgren G, Richman S, Pace A, Lee S, Schlain B, Campagnolo D, Belachew S, Ticho B

Ann Neurol. 2014 Oct 1. PMID: 25273271. Abstract

Associated with a risk of progressive multifocal leukoencephalopathy (PML); a very low percentage of L-selectin-expressing CD4+ T cells is highly correlated with a risk for PML, indicating a possible biomarker for risk

(104)

L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients.

Schwab N, Schneider-Hohendorf T, Posevitz V, Breuer J, Göbel K, Windhagen S, Brochet B, Vermersch P, Lebrun-Frenay C, Posevitz-Fejfár A, et al.

Neurology. 2013 Sep 3; 81(10):865-71. Epub 2013 Aug 07. PMID: 23925765. Abstract

Associated with a risk of progressive multifocal leukoencephalopathy (PML); a correlation between the level of soluble L-selectin and the anti-JC virus antibody index in the sera of natalizumab-treated (but not interferon beta-treated) individuals with RRMS has been observed, indicating that soluble L-selectin might serve as a biomarker for PML risk

(278)

Association between soluble L-selectin and anti-JCV antibodies in natalizumab-treated relapsing-remitting MS patients.

Basnyat P, Hagman S, Kolasa M, Koivisto K, Verkkoniemi-Ahola A, Airas L, Elovaara I

Mult Scler Relat Disord. 2015 Jul; 4(4):334-8. PMID: 26195052. Abstract

Associated with a risk of progressive multifocal leukoencephalopathy (PML); a single risk algorithm that incorporates both the anti-JC virus antibody index and L-selectin (CD62L) level may be useful for reducing the incidence of PML

(289)

PML risk stratification using anti-JCV antibody index and L-selectin.

Schwab N, Schneider-Hohendorf T, Pignolet B, Spadaro M, Görlich D, Meinl I, Windhagen S, Tackenberg B, Breuer J, Cantó E, et al.

Mult Scler. 2015 Oct 2. PMID: 26432858. Abstract

A risk of natalizumab-associated progressive multifocal leukoencephalopathy (PML) is not predicted by the percentage of CD3+ CD4+ CD62L+ cells in cryopreserved peripheral blood mononuclear cells (PBMCs), as shown in a study of cell samples from 21 individuals treated with natalizumab who developed PML and 104 matched individuals who did not

(303)

CD62L is not a reliable biomarker for predicting PML risk in natalizumab-treated R-MS patients.

Lieberman LA, Zeng W, Singh C, Wang W, Otipoby KL, Loh C, Plavina T, Gorelik L, Ransohoff RM, Cahir-McFarland E

Neurology. 2015 Dec 30. PMID: 26718566. Abstract

Natalizumab-associated progressive multifocal leukoencephalopathy (PML) diagnosis might be improved by use of an anti-JC virus "antibody specificity index," a measure of the proportion of anti-JC virus antibodies in cerebrospinal fluid (CSF) versus serum (such that increased levels in CSF are associated with PML)

(128)

Antibody index test may aid PML diagnosis on natalizumab

Hughes S, Medscape, 30 Oct 2013

Accessed on 5 Nov 2013 from http://www.medscape.com/viewarticle/813469.

Estimated occurrence of progressive multifocal leukoencephalopathy (PML) among natalizumab-treated individuals with MS (with an average of 17 months of treatment) was 1 per 1000 in 2006; with more individuals receiving treatment for longer times, the occurrence is now about 1 per 330, but rises to 1 per 90 in those with additional PML risk factors (August 2013)

(105)

Risk factors for rare diseases can be risky to define: PML and natalizumab.

Major EO, Douek DC

Neurology. 2013 Aug 7. PMID: 23925759. Abstract

Risk for natalizumab-associated progressive multifocal leukoencephalopathy, based on the most recently available data, is higher in 2015 than in 2012, such that an individual with three risk factors (positive JC virus antibody status, >2 years of natalizumab therapy, and previous immunosuppressive therapy exposure) has ~1:44 chance of developing this disorder

(317)

Reassessing the risk of natalizumab-associated PML.

Berger JR, Fox RJ

J Neurovirol. 2016 Feb 3. Epub 2016 Feb 03. PMID: 26843383. Abstract

Model of natalizumab-associated progressive multifocal leukoencephalopathy risk in individuals who are sero-negative for JC virus has been developed

(130)

Modeling probability of additional cases of natalizumab-associated JCV sero-negative progressive multifocal leukoencephalopathy.

Carruthers RL, Chitnis T, Healy BC

Mult Scler. 2013 Nov 4. PMID: 24189572. Abstract

Immune reconstitution inflammatory syndrome occurred in a natalizumab-treated patient with progressive multifocal leukoencephalopathy

(97)

Immune reconstitution inflammatory syndrome in a patient treated with natalizumab presenting progressive multifocal leukoencephalopathy.

Métivier D, Arnaud F-X, Dutasta F, Nguema B, Teriitehau C, Berets O, Baccialone J, Potet J

Diagn Interv Imaging. 2013 Jan; 94(1):101-3. Epub 2012 Dec 08. PMID: 23228283. Abstract

Initiation of progressive multifocal leukoencephalopathy and reconstitution inflammatory syndrome in natalizumab-treated individuals with MS is associated with or preceded by clonal T cell expansions

(115)

Natalizumab affects the T-cell receptor repertoire in patients with multiple sclerosis.

Warnke C, Mausberg AK, Stettner M, Dehmel T, Nekrich L, Meyer Zu Horste G, Hartung H-P, Fogdell-Hahn A, Adams O, Kieseier BC

Neurology. 2013 Sep 18. PMID: 24049136. Abstract

(116)

A bird's-eye view of T cells during natalizumab therapy.

Hohlfeld R, Stüve O

Neurology. 2013 Sep 18. PMID: 24049137. Abstract

Natalizumab-related risk for progressive multifocal leukoencephalopathy appears to be lower in individuals with lipid-specific IgM antibodies in the cerebrospinal fluid

(120)

IgM antibody identifies good candidates for natalizumab

Hughes S, Medscape, 8 Oct 2013

Accessed on 10 Oct 2013 from http://www.medscape.com/viewarticle/812244.

Despite the increased risk of natalizumab-associated progressive multifocal leukoencephalopathy in individuals positive for JC virus antibodies, the decision to continue natalizumab treatment is largely unaffected by JC virus antibody status, based on a study of 112 individuals

(121)

Does jcv antibody positivity encourage cessation of natalizumab therapy in multiple sclerosis?

Lonergan R, Kinsella K, Kelly S, Duggan M, Scott J, O'Rourke K, Lynch T, Hutchinson M, Tubridy N, McGuigan C

J Neurol Neurosurg Psychiatry. 2013 Nov; 84(11):e2. PMID: 24108958. Abstract

Risk of natalizumab-associated progressive multifocal leukoencephalopathy may be increased by splenectomy, on the basis of a single case study

(122)

Immunological and clinical consequences of splenectomy in a multiple sclerosis patient treated with natalizumab.

Lee D-H, Waschbisch A, Lämmer AB, Doerfler A, Schwab S, Linker RA

J Neuroinflammation. 2013 Oct 9; 10(1):123. Epub 2013 Oct 09. PMID: 24107235. Abstract

Associated with progressive multifocal leukoencephalopathy (PML), but in one postmortem study of an individual with MS who developed PML after natalizumab therapy, the extensive PML lesions (which contained JC virus DNA), located in the neocortex and cerebral white matter, were distinct and separate from chronic inactive MS lesions nearby

(124)

Natalizumab-associated progressive multifocal leukoencephalopathy in a patient with multiple sclerosis: a postmortem study.

Wüthrich C, Popescu B GF, Gheuens S, Marvi M, Ziman R, Denq S P, Tham M, Norton E, Parisi JE, Dang X, et al.

J Neuropathol Exp Neurol. 2013 Nov; 72(11):1043-51. PMID: 24128680. Abstract

Associated with progressive multifocal leukoencephalopathy (PML); in one individual with RRMS treated with natalizumab, brainstem lesions were first interpreted to be MS plaques, but later became confluent and were identified as a PML lesion

(125)

Brainstem PML lesion mimicking MS plaque in a natalizumab-treated MS patient.

Tortorella C, Direnzo V, D'Onghia M, Trojano M

Neurology. 2013 Oct 15; 81(16):1470-1. PMID: 24127190. Abstract

Occurrence of progressive multifocal leukoencephalopathy (PML) within 6 months after discontinuation of natalizumab for reasons not related to suspected PML has been documented in 17 patients, most (16) of whom were determined to have had at least 1 risk factor for PML at the time of natalizumab withdrawal

(131)

Progressive multifocal leukoencephalopathy after natalizumab discontinuation.

Fine AJ, Sorbello A, Kortepeter C, Scarazzini L

Ann Neurol. 2013 Nov 16. PMID: 24242357. Abstract

JC virus-negative natalizumab-associated progressive multifocal leukoencephalopathy has been diagnosed

(140)

JCV-negative natalizumab-associated progressive multifocal leukoencephalopathy: a clinico-radiological diagnosis.

Travasarou M, Marousi S, Papageorgiou E, Karageorgiou CE

Clin Neurol Neurosurg. 2013 Jun; 115(6):827-9. Epub 2012 Aug 21. PMID: 22920632. Abstract

Association with a risk for progressive multifocal leukoencephalopathy has led to natalizumab's use as a second-line therapy; an algorithm has been developed to select individuals for whom use as a first-line therapy might be appropriate

(156)

First-line natalizumab in multiple sclerosis: rationale, patient selection, benefits and risks.

Nicholas J A, Racke M K, Imitola J, Boster A L

Ther Adv Chronic Dis. 2014 Mar; 5(2):62-68. PMID: 24587891. Abstract

Outcomes of either discontinuing natalizumab or obtaining additional screening in those at risk for natalizumab-associated progressive multifocal leukoencephalopathy have been described with decision tree models

(159)

Benefit of additional screening for progressive multifocal leukoencephalopathy in patients with multiple sclerosis taking natalizumab: a decision analysis.

Landy DC, Hecht EM

Clin Neuropharmacol. 2014 Mar-Apr; 37(2):45-51. PMID: 24614671. Abstract

Benefit of continuing natalizumab treatment appears to outweigh the risk of progressive multifocal leukoencephalopathy for most individuals according to theoretical calculations

(159)

Benefit of additional screening for progressive multifocal leukoencephalopathy in patients with multiple sclerosis taking natalizumab: a decision analysis.

Landy DC, Hecht EM

Clin Neuropharmacol. 2014 Mar-Apr; 37(2):45-51. PMID: 24614671. Abstract

More than 400 cases of natalizumab-associated progressive multifocal leukoencephalopathy have occurred as of March 2014

(160)

Natalizumab to fingolimod washout in patients at risk of PML: When good intentions yield bad outcomes.

Giovannoni G, Naismith RT

Neurology. 2014 Mar 7. PMID: 24610331. Abstract

During prolonged natalizumab therapy, asymptomatic JC virus reactivation can occur in the cerebrospinal fluid

(167)

JC virus Reactivation During Prolonged Natalizumab Monotherapy for Multiple Sclerosis.

Chalkias S, Dang X, Bord E, Stein MC, Kinkel PR, Sloane JA, Donnelly M, Ionete C, Houtchens MK, Buckle GJ, et al.

Ann Neurol. 2014 Mar 31. PMID: 24687904. Abstract

Differences between natalizumab-associated progressive multifocal leukoencephalopathy with and without initial manifestations in infratentorial brain structures have been described

(170)

Clinical and paraclinical findings in natalizumab-associated infratentorial progressive multifocal leukoencephalopathy patients.

Hoepner R, Ahlbrecht J, Faissner S, Schneider R, Dahlhaus S, Adams O, Raab P, Lukas C, Chan A, Stangel M, et al.

J Neurol Neurosurg Psychiatry. 2014 Apr 3. PMID: 24700881. Abstract

Three factors (anti-JC virus antibodies, previous use of immunosuppressants, and length of natalizumab therapy) have been found to contribute to the risk of natalizumab-associated progressive multifocal leukoencephalopathy (PML), but risk stratification did not reduce the incidence of PML in natalizumab-treated individuals with MS in the period between April 2010 and February 2014

(179)

Does risk stratification decrease the risk of natalizumab-associated PML? Where is the evidence?

Cutter GR, Stüve O

Mult Scler. 2014 May 8. PMID: 24812045. Abstract

Individual risk of natalizumab-associated progressive multifocal leukoencephalopathy might potentially be assessed by monitoring the expression of certain microRNAs (miR-320, miR-320b, and miR-629) in blood samples

(184)

Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients.

Muñoz-Culla M, Irizar H, Castillo-Triviño T, Sáenz-Cuesta M, Sepúlveda L, Lopetegi I, de Munain LA, Olascoaga J, Baranzini SE, Otaegui D

Mult Scler. 2014 May 22. PMID: 24852919. Abstract

Associated with a risk of developing progressive multifocal leukoencephalopathy; 430 cases have been reported to date (July 2014)

(206)

JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients.

Delbue S, Elia F, Carloni C, Pecchenini V, Franciotta D, Gastaldi M, Colombo E, Signorini L, Carluccio S, Bellizzi A, et al.

J Neurovirol. 2014 Jul 23. Epub 2014 Jul 23. PMID: 25052191. Abstract

Associated with a risk of developing progressive multifocal leukoencephalopathy, especially in individuals seropositive for JC virus (JCV); individuals can be seronegative for JCV (based on serological tests) but still shed JCV DNA into the urine; furthermore, natalizumab might accelerate JCV shedding into the urine

(206)

JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients.

Delbue S, Elia F, Carloni C, Pecchenini V, Franciotta D, Gastaldi M, Colombo E, Signorini L, Carluccio S, Bellizzi A, et al.

J Neurovirol. 2014 Jul 23. Epub 2014 Jul 23. PMID: 25052191. Abstract

Associated with progressive multifocal leukoencephalopathy (PML); the number of plasmapheresis/immunoadsorption treatments (important for PML outcome) required to reach subtherapeutic serum natalizumab concentrations varies depending on the serum natalizumab concentration at the time of PML diagnosis

(208)

Application of serum natalizumab levels during plasma exchange in MS patients with progressive multifocal leukoencephalopathy.

Vennegoor A, Rispens T, Van Oosten B, Wattjes MP, Wondergem M, Teunissen CE, Van der Kleij D, Uitdehaag BMJ, Polman CH, Killestein J

Mult Scler. 2014 Jul 30. PMID: 25078275. Abstract

Asymptomatic natalizumab-associated progressive multifocal leukoencephalopathy manifests as relatively localized disease on MRI, often affecting the frontal lobe, based on a study of 18 individuals with MS

(216)

MRI pattern in asymptomatic natalizumab-associated PML.

Wattjes MP, Vennegoor A, Steenwijk MD, de Vos M, Killestein J, van Oosten BW, Mostert J, Siepman DA, Moll W, van Golde AEL, et al.

J Neurol Neurosurg Psychiatry. 2014 Sep 9. PMID: 25205744. Abstract

Early natalizumab-associated progressive multifocal leukoencephalopathy (PML) with immune reconstitution inflammatory syndrome exhibits certain characteristics in MRI; the most common first sign is patchy or punctate contrast enhancement in the border of the PML lesion, based on a retrospective study of 26 individuals with MS

(284)

MRI characteristics of early PML-IRIS after natalizumab treatment in patients with MS.

Wattjes MP, Wijburg MT, Vennegoor A, Witte BI, de Vos M, Richert ND, Uitdehaag B M, Barkhof F, Killestein J, Dutch-Belgian Natalizumab-associated PML study group

J Neurol Neurosurg Psychiatry. 2015 Sep 14. PMID: 26369555. Abstract

Natalizumab-associated progressive multifocal leukoencephalopathy (PML) is associated with a punctate pattern in MRI, as shown in a study of 20 individuals with PML, and this pattern might represent the first imaging feature detectable during presymmptomatic stages of PML

(330)

Punctate pattern: A promising imaging marker for the diagnosis of natalizumab-associated PML.

Hodel J, Darchis C, Outteryck O, Verclytte S, Deramecourt V, Lacour A, Zins M, Pruvo J-P, Vermersch P, Leclerc X

Neurology. 2016 Mar 23. PMID: 27009257. Abstract

Natalizumab-associated asymptomatic progressive multifocal leukoencephalopathy (PML) is associated with certain features in MRI; the most predictive features are hyperintensity on diffusion-weighted images and U fiber involvement, as shown in a retrospective study of 11 individuals with MS with such a diagnosis and 40 individuals with MS treated with natalizumab but without PML

(288)

Asymptomatic Progressive Multifocal Leukoencephalopathy Associated with Natalizumab: Diagnostic Precision with MR Imaging.

Hodel J, Outteryck O, Dubron C, Dutouquet B, Benadjaoud M A, Duhin E, Verclytte S, Zins M, Luciani A, Rahmouni A, et al.

Radiology. 2015 Oct 5:150673. PMID: 26436861. Abstract

Natalizumab-associated progressive multifocal leukoencephalopathy (PML) is preceded by high serum anti-JC virus antibody indexes, although an increase just before PML diagnosis was not observed, as shown by a longitudinal study in 4 individuals with MS who developed PML

(245)

Longitudinal JCV serology in multiple sclerosis patients preceding natalizumab-associated progressive multifocal leukoencephalopathy.

Vennegoor A, van Rossum JA, Polman CH, Wattjes MP, Killestein J

Mult Scler. 2015 Feb 6. PMID: 25662344. Abstract

Increases the risk of developing progressive multifocal leukoencephalopathy, which requires exposure to JC virus; the JC virus antibody index correlates with ultrasensitive C-reactive protein serum levels and with JC virus DNA levels in the urine

(222)

JC virus antibody index in natalizumab-treated patients: correlations with John Cunningham virus DNA and C-reactive protein level.

Lanzillo R, Liuzzi R, Vallefuoco L, Moccia M, Amato L, Vacca G, Vacchiano V, Portella G, Brescia Morra V

Ther Clin Risk Manag. 2014; 10:807-14. Epub 2014 Oct 09. PMID: 25328396. Abstract

Individuals with natalizumab-associated progressive multifocal leukoencephalopathy (PML) exhibit low total IgG levels in blood and cerebrospinial fluid at the time of PML diagnosis

(230)

Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF.

Warnke C, Stettner M, Lehmensiek V, Dehmel T, Mausberg AK, von Geldern G, Gold R, Kümpfel T, Hohlfeld R, Mäurer M, et al.

Mult Scler. 2014 Nov 12. PMID: 25392339. Abstract

Survival and disability outcomes for individuals with natalizumab-associated progressive multifocal leukoencephalopathy (PML) are better for those who are asymptomatic at the time of PML diagnosis (by MRI and JC virus detection) than for those who are symptomatic

(234)

Outcome and survival of asymptomatic PML in natalizumab-treated MS patients.

Dong-Si T, Richman S, Wattjes MP, Wenten M, Gheuens S, Philip J, Datta S, McIninch J, Bozic C, Bloomgren G, et al.

Ann Clin Transl Neurol. 2014 Oct; 1(10):755-64. Epub 2014 Oct 09. PMID: 25493267. Abstract

Progressive multifocal leukoencephalopathy (PML)-immune reconstitution inflammatory syndrome was diagnosed in an individual after the discontinuation of natalizumab (at which time PML was missed by MRI) and the initiation of fingolimod

(236)

PML-IRIS during Fingolimod Diagnosed after Natalizumab Discontinuation.

Killestein J, Vennegoor A, van Golde AEL, Bourez RLJH, Wijlens MLB, Wattjes MP

Case Rep Neurol Med. 2014; 2014:307872. Epub 2014 Nov 23. PMID: 25506447. Abstract

Risk of natalizumab-associated progressive multifocal leukoencephalopathy (PML) is lower in individuals with lipid-specific IgM oligoclonal bands in cerebrospinal fluid (a marker of highly inflammatory MS), as shown in a study of 24 individuals who developed PML and 343 who did not

(241)

lipid-specific IgM bands in csf associated with a reduced risk of developing pml during treatment with natalizumab.

Villar LM, Costa-Frossard L, Masterman T, Fernandez O, Montalban X, Casanova B, Izquierdo G, Coret F, Tumani H, Saiz A, et al.

Ann Neurol. 2015 Jan 7. PMID: 25581547. Abstract

Survival of natalizumab-associated progressive multifocal leukoencephalopathy is more likely in those who are younger at diagnosis and have lower Expanded Disability Status Scale scores before diagnosis, lower loads of JC virus in the cerebrospinal fluid at diagnosis, less functional disability in general, and localized rather than widespread disease at diagnosis as assessed by MRI, as shown in a study of 336 individuals, 76% of whom survived this condition

(252)

Predictors of survival and functional outcomes in natalizumab-associated progressive multifocal leukoencephalopathy.

Dong-Si T, Gheuens S, Gangadharan A, Wenten M, Philip J, McIninch J, Datta S, Richert N, Bozic C, Bloomgren G, et al.

J Neurovirol. 2015 Mar 14. Epub 2015 Mar 14. PMID: 25771865. Abstract

Risk of natalizumab-associated progressive multifocal leukoencephalopathy might be lower in pediatric versus adult MS patients, because the seroprevalence of JC virus antibody is lower in this pediatric population (33.3%) than reported in adults (60%), as shown in a study of 109 pediatric MS patients

(294)

Age-Dependent Seroprevalence of JCV Antibody in Children.

Hennes E M, Kornek B, Huppke P, Reindl M, Rostasy K, Berger T

Neuropediatrics. 2015 Oct 19. Epub 2015 Oct 19. PMID: 26479766. Abstract

In a case of severe natalizumab-associated progressive multifocal leukoencephalopathy (PML), four neurotropic variants of the JC virus were detected in blood cells, serum, and urine, suggesting that detection of such a variant in blood might aid in the prevention of severe PML

(297)

Monitoring the John Cunningham virus throughout natalizumab treatment in multiple sclerosis patients.

Domínguez-Mozo MI, García-Montojo M, Arias-Leal A, García-Martínez Á, Santiago JL, Casanova I, Galán V, Arroyo R, Fernández-Arquero M, Alvarez-Lafuente R

Eur J Neurol. 2015 Oct 25. PMID: 26498276. Abstract

Natalizumab-associated progressive multifocal leukoencephalopathy (PML) has been reported in an individual using extended dosing intervals (300 mg every 6 weeks), a method that has been suggested for lowering the risk of PML

(298)

Progressive multifocal leukoencephalopathy associated to natalizumab extended dosing regimen.

Hervás J V, Presas-Rodríguez S, Crespo-Cuevas A M, Canento T, Lozano-Sánchez M, Massuet-Vilamajó A, Ramo-Tello C

Neurodegener Dis Manag. 2015 Oct 30. PMID: 26517599. Abstract

Natalizumab-associated early progressive multifocal leukoencephalopathy (PML) lesions were distinguished from MS lesions by 7T MRI in a case in which PML and ongoing MS activity presented simultaneously

(299)

7T MRI in natalizumab-associated PML and ongoing MS disease activity: A case study.

Sinnecker T, Othman J, Kühl M, Mekle R, Selbig I, Niendorf T, Kunkel A, Wienecke P, Kern P, Paul F, et al.

Neurol Neuroimmunol Neuroinflamm. 2015 Dec; 2(6):e171. Epub 2015 Oct 29. PMID: 26568970. Abstract

Associated with a high annualized rate of seroconversion for anti-JC virus antibodies (7.1%, with a cumulative seroconversion rate of >25% over 4 years), as shown in a Dutch cohort of 179 individuals with RRMS; such seropositivity is a risk factor for natalizumab-associated progressive multifocal leukoencephalopathy

(325)

High cumulative JC virus seroconversion rate during long-term use of natalizumab.

Vennegoor A, van Rossum J, Leurs C, Wattjes MP, Rispens T, Murk JLAN, Uitdehaag BMJ, Killestein J

Eur J Neurol. 2016 Mar 27. PMID: 27018481. Abstract

Might increase seroconversion to positive JC virus antibody status, and increase JC virus index values, as shown in a study of 525 German and 711 French individuals with MS who were followed longitudinally (such that 10.3% of the German group and 8.5% of the French group converted per year); such seropositivity is a risk factor for natalizumab-associated progressive multifocal leukoencephalopathy

(331)

Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values.

Schwab N, Schneider-Hohendorf T, Pignolet B, Breuer J, Gross CC, Göbel K, Brassat D, Wiendl H

Neurol Neuroimmunol Neuroinflamm. 2016 Feb; 3(1):e195. Epub 2016 Jan 27. PMID: 26848486. Abstract

Aggravated psoriasis in one patient

(47)

Psoriasis during natalizumab treatment for multiple sclerosis.

Millán-Pascual J, Turpín-Fenoll L, Del Saz-Saucedo P, Rueda-Medina I, Navarro-Muñoz S

J Neurol. 2012 Oct 25. Epub 2012 Oct 25. PMID: 23096069. Abstract

Rash

(3)

ACUTE RETINAL NECROSIS AND IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME IN A NATALIZUMAB-TREATED PATIENT WITH MULTIPLE SCLEROSIS.

Biogen Idec and Elan Pharmaceuticals

Acute retinal necrosis, followed by immune reconstitution inflammatory syndrome, has been reported in an individual with MS treated with natalizumab

(262)

Saraiva VS

Retin Cases Brief Rep. 2015 Apr 29. PMID: 25933353. Abstract

Progressive outer retinal necrosis has been reported in an individual with MS being treated with natalizumab

(308)

Progressive outer retinal necrosis in a multiple sclerosis patient on natalizumab.

Bourre B, Gueudry J, Lefaucheur R, Borden A, Maltête D, Patel SS, Van Tassel S H, Gupta MP, Orlin A, Nealon NM

Neurology. 2016 Jan 19; 86(3):312-3. PMID: 26783270. Abstract

Reversible leukoencephalopathy syndrome (which can mimic progressive multifocal leukoencephalopathy)

(26)

Natalizumab-associated reversible encephalopathy syndrome mimicking progressive multifocal leukoencephalopathy.

Décard BF, Haghikia A, Tönnes C, Thöne J, Lukas C, Chan A, Gold R

Mult Scler. 2012 May 17. PMID: 22596228. Abstract

Stomach pain

(3)

A possible case of natalizumab-dependent suicide attempt: A brief review about drugs and suicide.

Biogen Idec and Elan Pharmaceuticals

Suicidal ideation might be an uncommon secondary effect of treatment (suicidal behavior has been observed in one individual with MS who was being treated with natalizumab)

(135)

Mumoli L, Ciriaco M, Gambardella A, Bombardiere G N, Valentino P, Palleria C, Labate A, Russo E

J Pharmacol Pharmacother. 2013 Dec; 4(Suppl 1):S90-3. PMID: 24347991. Abstract

Cyclical suicidal ideation after infusion for MS has been reported

(246)

Cyclical suicidal ideation following natalizumab infusion for multiple sclerosis.

Nagesh O, Bastiampillai T, Fisher L, Mohan T

Aust N Z J Psychiatry. 2015 Feb 16. PMID: 25688123. Abstract

Urinary tract infection

(3)

Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study.

Biogen Idec and Elan Pharmaceuticals

Reduced the efficacy of vaccination against pandemic H1N1 (swine flu, in 2009) and seasonal influenza (in 2010)

(143)

Olberg HK, Cox RJ, Nostbakken JK, Aarseth JH, Vedeler CA, Myhr K-M

Mult Scler. 2014 Jan 16. PMID: 24436455. Abstract

Vaginitis

(3)

Varicella zoster-associated retinal and central nervous system vasculitis in a patient with multiple sclerosis treated with natalizumab.

Biogen Idec and Elan Pharmaceuticals

Associated with combined retinal and central nervous system vasculitis, which was linked with varicella zoster, in one individual

(146)

Kobeleva X, Wegner F, Brunotte I, Dadak M, Dengler R, Stangel M

J Neuroinflammation. 2014; 11(1):19. Epub 2014 Jan 30. PMID: 24479415. Abstract

Might increase the risk of subclinical varicella-zoster virus (VZV) reactivation or reinfection, based on the increased incidence of elevated levels of anti-VZV IgG in natalizumab-treated individuals with MS

(255)

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis.

Kohlmann R, Salmen A, Chan A, Knabbe C, Diekmann J, Brockmeyer N, Skaletz-Rorowski A, Michalik C, Gold R, Überla K

Mult Scler. 2015 Mar 31. PMID: 25828755. Abstract

Wheezing

(3)

Natalizumab treatment during pregnancy - effects on the neonatal immune system.

Biogen Idec and Elan Pharmaceuticals

Use in pregnancy was associated with a reduction in CXCL12-induced T-cell chemotaxis in neonates in two cases, a change that might compromise the neonatal immune system

(34)

Schneider H, Weber CE, Hellwig K, Schroten H, Tenenbaum T

Acta Neurol Scand. 2012 Sep 5. PMID: 22950358. Abstract

Use during the entire gestational period was not associated with any problems in the pregnancy or resulting child in one case

(152)

Normal outcome of pregnancy with ongoing treatment with natalizumab.

Fagius J, Burman J

Acta Neurol Scand. 2014 Feb 15. PMID: 24527849. Abstract

Use during the third trimester of pregnancy caused modest hematological alterations that included thrombocytopenia and anemia in 10 of 13 infants monitored

(180)

Natalizumab Use During the Third Trimester of Pregnancy.

Haghikia A, Langer-Gould A, Rellensmann G, Schneider H, Tenenbaum T, Elias-Hamp B, Menck S, Zimmermann J, Herbstritt S, Marziniak M, et al.

JAMA Neurol. 2014 May 12. PMID: 24821217. Abstract

Transferred to, and appeared to accumulate in, breast milk in one woman with MS who was breastfeeding her infant, but the safety of this effect was not determined

(240)

Transfer of Natalizumab into Breast Milk in a Mother with Multiple Sclerosis.

Baker TE, Cooper SD, Kessler L, Hale TW

J Hum Lact. 2015 Jan 13. PMID: 25586712. Abstract

Associated with drug-induced immune thrombocytopenia in one case

(192)

Drug-induced thrombocytopenia secondary to natalizumab treatment.

Cachia D, Izzy S, Berriosmorales I, Ionete C

BMJ Case Rep. 2014; 2014. PMID: 24879724. Abstract

Concomitant use of fingolimod or natalizumab is not associated with complications of Dengue fever in individuals with MS, as shown in a study of 15 individuals

(327)

Dengue fever in patients with multiple sclerosis taking fingolimod or natalizumab.

Fragoso Y D, da Gama P D, Gomes S, Khouri J M N, da Matta A P C, Mendes M F, Stella C R A V

Mult Scler Relat Disord. 2016 Mar; 6:64-5. Epub 2016 Jan 28. PMID: 27063625. Abstract

Discontinuation of treatment led to progressive multifocal encephalopathy immune reconstitution inflammatory syndrome and related malignant cerebral edema in an individual with MS

(272)

Surgical management of malignant cerebral edema secondary to immune reconstitution inflammatory syndrome from natalizumab-associated progressive multifocal encephalopathy.

Tan LA, Lopes DK

J Clin Neurosci. 2015 Jun 24. PMID: 26115897. Abstract

Cessation of natalizumab [to avoid risk of progressive multifocal leukoencephalopathy (PML) or because PML was detected] was associated with immune reconstitution inflammatory syndrome in four cases; the case in which no PML was detected was fatal

(316)

Immune-Reconstitution Inflammatory Syndrome in Multiple Sclerosis Patients Treated With Natalizumab: A Series of 4 Cases.

N'gbo N'gbo Ikazabo R, Mostosi C, Quivron B, Delberghe X, El Hafsi K, Lysandropoulos AP

Clin Ther. 2016 Feb 4. PMID: 26856928. Abstract

End of dosing cycle is associated with a return of MS symptoms (such as fatigue, weakness, impaired walking, and difficulties with cognition) in about two thirds of those receiving treatment, based on a study of 100 individuals; such symptoms began a median of 21 days after infusion

(204)

Multiple sclerosis symptom recrudescence at the end of the natalizumab dosing cycle.

Ratchford JN, Brock-Simmons R, Augsburger A, Steele SU, Mohn K, Rhone M, Bo J, Costello K

Int J MS Care. 2014 Summer; 16(2):92-8. PMID: 25061433. Abstract

Discontinuations (due to pregnancy planning) led to recurrent disease-activity rebound in an MS patient

(95)

Recurrent disease-activity rebound in a patient with multiple sclerosis after natalizumab discontinuations for pregnancy planning.

Martinelli V, Colombo B, Dalla Costa G, Dalla Libera D, Moiola L, Falini A, Comi G, Filippi M

Mult Scler. 2013 Jun 17. PMID: 23773984. Abstract

Discontinuation during pregnancy was associated with a strong increase in disability and a high load of MRI lesions in 4 women with MS, despite the fact that pregnancy is generally associated with disease stability

(243)

Natalizumab discontinuation and disease restart in pregnancy: a case series.

De Giglio L, Gasperini C, Tortorella C, Trojano M, Pozzilli C

Acta Neurol Scand. 2015 Jan 18. PMID: 25598313. Abstract

Discontinuation due to pregnancy leads to strong rebound activity (resulting in a relapse rate of 32.2% in this study), indicating that the protective effects of pregnancy do not extend to this situation, based on an analysis of 59 women who discontinued natalizumab during pregnancy (meeting report)

(291)

Pregnancy Does Not Prove Neuroprotective for Women with MS Who Stop Taking Natalizumab

Susman E, Neurology Today, 9 Oct 2015

Accessed on 13 Oct 2015 from http://journals.lww.com/neurotodayonline/blog/NeurologyTodayConferenceReportersCongressofECTRIMS/pages/post.aspx?PostID=4.

Withdrawal led to a lethal MS relapse in one patient

(48)

LETHAL MULTIPLE SCLEROSIS RELAPSE AFTER NATALIZUMAB WITHDRAWAL.

Rigau V, Mania A, Béfort P, Carlander B, Jonquet O, Lassmann H, Camu W, Thouvenot E

Neurology. 2012 Oct 24. PMID: 23100404. Abstract

Cessation of treatment is followed by relapses (with a cumulative probability of 52.9% in the year after cessation) associated with abnormal inflammatory activity (>5 gadolinium-enhancing lesions, exceeding the number before treatment), as shown in a study of 32 individuals with MS

(185)

Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis.

Gueguen A, Roux P, Deschamps R, Moulignier A, Bensa C, Savatovsky J, Heran F, Gout O

J Neurol Neurosurg Psychiatry. 2014 May 29. PMID: 24876183. Abstract

Withdrawal from long-term treatment, followed by a single dose after a relapse beginning 3 months after withdrawal, was associated with a massive exacerbation of MS symptoms in one individual

(214)

Massive exacerbation of multiple sclerosis after withdrawal and early restart of treatment with natalizumab.

Beume L-A, Dersch R, Fuhrer H, Stich O, Rauer S, Niesen WD

J Clin Neurosci. 2014 Aug 20. PMID: 25150761. Abstract

Each of two episodes of natalizumab discontinuation in a study of 15 individuals was followed by disease reactivation, despite immunomodulant treatment (after the first withdrawal) or a second-line therapy such as fingolimod (after the second withdrawal)

(219)

Recurrence of disease activity after repeated Natalizumab withdrawals.

Ferrè L, Moiola L, Sangalli F, Radaelli M, Barcella V, Comi G, Martinelli V

Neurol Sci. 2014 Sep 24. Epub 2014 Sep 24. PMID: 25249399. Abstract

After natalizumab withdrawal, significant clinical worsening is associated with a higher Expanded Disability Status Scale (EDSS) score at baseline and with a 1-step increase in the EDSS during treatment

(232)

Significant clinical worsening after natalizumab withdrawal: Predictive factors.

Vidal-Jordana A, Tintoré M, Tur C, Pérez-Miralles F, Auger C, Río J, Nos C, Arrambide G, Comabella M, Galán I, et al.

Mult Scler. 2014 Nov 12. PMID: 25392320. Abstract

Treatment discontinuation (as a result of concerns about the risk of progressive multifocal leukoencephalopathy) is associated with a 1 in 3 risk of disability worsening, and that risk increases to 1 in 2 if the Expanded Disability Status Scale Score is >3 when treatment begins, based on a study of data from 318 individuals who did not exhibit worsening disability in the first 2 years of treatment and a followup time of 6 years

(248)

Natalizumab discontinuation in patients with multiple sclerosis: Profiling risk and benefits at therapeutic crossroads.

Prosperini L, Annovazzi P, Capobianco M, Capra R, Buttari F, Gasperini C, Galgani S, Solaro C, Centonze D, Bertolotto A, et al.

Mult Scler. 2015 Feb 19. PMID: 25698174. Abstract

Discontinuation is followed by a period of high risk for disease activation (between the second and eighth months), during which most individuals return to pre-natalizumab levels of disease activity and 10% exhibit rebound activity, and neither immunomodulant therapy nor fingolimod protects sufficiently against this activity, based on a study of 110 individuals

(258)

Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients.

Sangalli F, Moiola L, Ferrè L, Radaelli M, Barcella V, Rodegher M, Colombo B, Martinelli Boneschi F, Martinelli V, Comi G

Mult Scler Relat Disord. 2014 Jul; 3(4):520-6. Epub 2014 Apr 13. PMID: 25877065. Abstract

Commercial:

Jointly developed by Elan Pharmaceuticals and Biogen Idec

(9)

Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?

Davenport RJ, Munday JR

Drug Discov Today. 2007 Jul; 12(13-14):569-76. Epub 2007 Jun 26. PMID: 17631252. Abstract

Clinical trials sponsored by Biogen Idec and Elan Pharmaceuticals

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Manufactured by Biogen Idec

(14)

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

Distributed by Elan Pharmaceuticals

(14)

Biogen Idec to acquire full rights and control of Tysabri from Elan for upfront cash and contingent payments

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

; Biogen Idec will take full control of Tysabri in 2013

(65)

Biogen Idec, 6 Feb 2013

Accessed on 11 Feb 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1781970.

Available only through a special restricted distribution program (TOUCH), because of the risk of progressive multifocal leukoencephalopathy

(14)

Biogen Idec and Elan submit applications for first-line use of Tysabri in anti-JCV antibody negative patients with MS

Biogen Idec and Elan Pharmaceuticals, Sep 2011

Accessed on 21 Nov 2011 from http://www.tysabri.com/en_US/tysb/site/pdfs/TYSABRI-pi.pdf.

(62)

Biogen Idec, 16 Jan 2013

Accessed on 21 Jan 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1774946.

(65)

Biogen Idec to acquire full rights and control of Tysabri from Elan for upfront cash and contingent payments

Biogen Idec, 6 Feb 2013

Accessed on 11 Feb 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1781970.

Using some of the proceeds from the Tysabri restructuring, Elan Corporation will repurchase $1 billion of stock after the restructuring transaction with Biogen Idec is closed (22 February 2013)

(68)

Elan provides update post restructuring announcement of Tysabri collaboration

Elan Corporation, 22 Feb 2013

Accessed on 27 Feb 2013 from http://newsroom.elan.com/phoenix.zhtml?c=88326&p=irol-newsArticle&ID=1787913.

Full rights for and control of Tysabri have been purchased by Biogen Idec from Elan Pharmaceuticals (2 April 2013)

(83)

Biogen Idec completes purchase of full rights and control of Tysabri®

Biogen Idec, 2 Apr 2013

Accessed on 8 Apr 2013 from http://www.biogenidec.com/PRESS_RELEASE_DETAILS.aspx?ID=5981&ReqId=1802638.

Biogen Idec, which markets Tysabri, has changed its name to Biogen (23 March 2015)

(264)

Biogen Idec Becomes Biogen

Biogen, 23 Mar 2015

Accessed on 7 Apr 2015 from http://biogen.newshq.businesswire.com/press-release/corporate/biogen-idec-becomes-biogen.

Key Clinical Trials

Placebo-controlled Trials:

Trial name:

TOFINGO (meeting report, October 2013; publ May 2015)

(119)

Shorter washout reduces MS relapse switching off natalizumab

Hughes S, Medscape, 7 Oct 2013

Accessed on 10 Oct 2013 from http://www.medscape.com/viewarticle/812174.

(266)

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.

Kappos L, Radue E-W, Comi G, Montalban X, Butzkueven H, Wiendl H, Giovannoni G, Hartung H-P, Derfuss T, Naegelin Y, et al.

Neurology. 2015 May 29. Epub 1969 Dec 31. PMID: 26024899. Abstract

Phase:

Phase IV trial

(266)

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.

Kappos L, Radue E-W, Comi G, Montalban X, Butzkueven H, Wiendl H, Giovannoni G, Hartung H-P, Derfuss T, Naegelin Y, et al.

Neurology. 2015 May 29. Epub 1969 Dec 31. PMID: 26024899. Abstract

Study Design:

Company-sponsored, multicenter, randomized, double-blind, placebo-controlled trial to determine the optimum timing for beginning fingolimod treatment after discontinuation of natalizumab; individuals who had been treated with natalizumab for at least 6 months (and had reason to discontinue such as positive JC virus antibody status, a risk for progressive multifocal leukoencephalopathy) were randomized to the following regimens: a washout period of 8 weeks followed by 24 weeks of fingolimod, a washout period of 12 weeks (no therapy for 8 weeks followed by 4 weeks of placebo) followed by 20 weeks of fingolimod, or a washout period of 16 weeks (no therapy for 8 weeks followed by 8 weeks of placebo) followed by 16 weeks of fingolimod; the primary outcome was the number of active T2 lesions during the washout and first 8 weeks of fingolimod; brain MRIs were obtained at baseline and weeks 8, 12, 16, 20, and 24

(119)

Shorter washout reduces MS relapse switching off natalizumab

Hughes S, Medscape, 7 Oct 2013

Accessed on 10 Oct 2013 from http://www.medscape.com/viewarticle/812174.

(266)

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.

Kappos L, Radue E-W, Comi G, Montalban X, Butzkueven H, Wiendl H, Giovannoni G, Hartung H-P, Derfuss T, Naegelin Y, et al.

Neurology. 2015 May 29. Epub 1969 Dec 31. PMID: 26024899. Abstract

Disease Stage:

RRMS

(266)

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.

Kappos L, Radue E-W, Comi G, Montalban X, Butzkueven H, Wiendl H, Giovannoni G, Hartung H-P, Derfuss T, Naegelin Y, et al.

Neurology. 2015 May 29. Epub 1969 Dec 31. PMID: 26024899. Abstract

Enrollment/Number of Patients:

142, with 112 completing the trial

(119)

Shorter washout reduces MS relapse switching off natalizumab

Hughes S, Medscape, 7 Oct 2013

Accessed on 10 Oct 2013 from http://www.medscape.com/viewarticle/812174.

(266)

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.

Kappos L, Radue E-W, Comi G, Montalban X, Butzkueven H, Wiendl H, Giovannoni G, Hartung H-P, Derfuss T, Naegelin Y, et al.

Neurology. 2015 May 29. Epub 1969 Dec 31. PMID: 26024899. Abstract

Duration:

32 weeks from the last natalizumab infusion

(266)

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.

Kappos L, Radue E-W, Comi G, Montalban X, Butzkueven H, Wiendl H, Giovannoni G, Hartung H-P, Derfuss T, Naegelin Y, et al.

Neurology. 2015 May 29. Epub 1969 Dec 31. PMID: 26024899. Abstract

Status/Outcome:

8- and 12-week washout periods were associated with fewer active T2 lesions during washout and the first 8 weeks of fingolimod (2.1 and 1.7 versus 8.2 for the 16-week washout) and a higher percentage of relapse-free individuals (88% and 91% versus 84% for the 16-week washout) during the 24 weeks since the last natalizumab treatment

(119)

Shorter washout reduces MS relapse switching off natalizumab

Hughes S, Medscape, 7 Oct 2013

Accessed on 10 Oct 2013 from http://www.medscape.com/viewarticle/812174.

(266)

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.

Kappos L, Radue E-W, Comi G, Montalban X, Butzkueven H, Wiendl H, Giovannoni G, Hartung H-P, Derfuss T, Naegelin Y, et al.

Neurology. 2015 May 29. Epub 1969 Dec 31. PMID: 26024899. Abstract

Trial name:

Fox et al., Neurology, April 2014 study (RESTORE)

(165)

MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study.

Fox RJ, Cree BAC, De Sèze J, Gold R, Hartung H-P, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, et al.

Neurology. 2014 Apr 9. Epub 2014 Mar 28. PMID: 24682966. Abstract

(302)

Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE.

Kaufman M, Cree BAC, De Sèze J, Fox RJ, Gold R, Hartung H-P, Jeffery D, Kappos L, Montalbán X, Weinstock-Guttman B, et al.

J Neurol. 2015 Feb; 262(2):326-36. Epub 2014 Nov 09. PMID: 25381458. Abstract

Phase:

Exploratory study

(165)

MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study.

Fox RJ, Cree BAC, De Sèze J, Gold R, Hartung H-P, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, et al.

Neurology. 2014 Apr 9. Epub 2014 Mar 28. PMID: 24682966. Abstract

Study Design:

Industry-funded, randomized, partially placebo-controlled exploratory study to examine disease activity in individuals who had been treated with natalizumab (with no relapse activity during the previous year and no gadolinium-enhancing lesions at the time of screening) during an interruption of natalizumab treatment; participants received either natalizumab, interferon beta-1a, glatiramer acetate, methylprednisolone, or placebo during the interruption

(165)

MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study.

Fox RJ, Cree BAC, De Sèze J, Gold R, Hartung H-P, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, et al.

Neurology. 2014 Apr 9. Epub 2014 Mar 28. PMID: 24682966. Abstract

(302)

Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE.

Kaufman M, Cree BAC, De Sèze J, Fox RJ, Gold R, Hartung H-P, Jeffery D, Kappos L, Montalbán X, Weinstock-Guttman B, et al.

J Neurol. 2015 Feb; 262(2):326-36. Epub 2014 Nov 09. PMID: 25381458. Abstract

Disease Stage:

RRMS

(165)

MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study.

Fox RJ, Cree BAC, De Sèze J, Gold R, Hartung H-P, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, et al.

Neurology. 2014 Apr 9. Epub 2014 Mar 28. PMID: 24682966. Abstract

Enrollment/Number of Patients:

175

(165)

MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study.

Fox RJ, Cree BAC, De Sèze J, Gold R, Hartung H-P, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, et al.

Neurology. 2014 Apr 9. Epub 2014 Mar 28. PMID: 24682966. Abstract

Duration:

24 weeks (length of interruption)

(165)

MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study.

Fox RJ, Cree BAC, De Sèze J, Gold R, Hartung H-P, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, et al.

Neurology. 2014 Apr 9. Epub 2014 Mar 28. PMID: 24682966. Abstract

Status/Outcome:

Interruption in natalizumab treatment was associated with an increased risk of MRI and relapse activity even when other therapies were used; relapses occurred in 4% of participants receiving natalizumab versus 15% to 29% of participants in other arms of the study

(165)

MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study.

Fox RJ, Cree BAC, De Sèze J, Gold R, Hartung H-P, Jeffery D, Kappos L, Kaufman M, Montalbán X, Weinstock-Guttman B, et al.

Neurology. 2014 Apr 9. Epub 2014 Mar 28. PMID: 24682966. Abstract

; during the randomized treatment period, gadolinium-enhancing lesions were observed in 0% of individuals receiving natalizumab, 48% of those receiving other treatments, and 61% of those on placebo; such lesions were primarily observed at week 16 or later

(302)

Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE.

Kaufman M, Cree BAC, De Sèze J, Fox RJ, Gold R, Hartung H-P, Jeffery D, Kappos L, Montalbán X, Weinstock-Guttman B, et al.

J Neurol. 2015 Feb; 262(2):326-36. Epub 2014 Nov 09. PMID: 25381458. Abstract

Trial name:

A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects with Secondary Progressive Multiple Sclerosis (ASCEND in SPMS) (press release, October 2015)

(145)

A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis (ASCEND in SPMS)

ClinicalTrials.gov, 12 Sep 2013

Accessed on 6 Feb 2014 from http://clinicaltrials.gov/show/NCT01416181.

(296)

Biogen Reports Top-Line Results from Phase 3 Study Evaluating Natalizumab in Secondary Progressive MS

Biogen, 21 Oct 2015

Accessed on 27 Oct 2015 from http://media.biogen.com/press-release/corporate/biogen-reports-top-line-results-phase-3-study-evaluating-natalizumab-seconda.

Phase:

Phase IIIb trial

(145)

A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis (ASCEND in SPMS)

ClinicalTrials.gov, 12 Sep 2013

Accessed on 6 Feb 2014 from http://clinicaltrials.gov/show/NCT01416181.

Study Design:

Industry-sponsored, multinational, randomized, double-blind, placebo-controlled study to examine the efficacy of intravenous natalizumab (300 mg every 4 weeks) on slowing disability accumulation that is not related to relapses, as measured by the Expanded Disability Status Scale or other tests (primary outcome measure)

(145)

A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis (ASCEND in SPMS)

ClinicalTrials.gov, 12 Sep 2013

Accessed on 6 Feb 2014 from http://clinicaltrials.gov/show/NCT01416181.

Disease Stage:

SPMS

(145)

A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis (ASCEND in SPMS)

ClinicalTrials.gov, 12 Sep 2013

Accessed on 6 Feb 2014 from http://clinicaltrials.gov/show/NCT01416181.

Enrollment/Number of Patients:

889

(296)

Biogen Reports Top-Line Results from Phase 3 Study Evaluating Natalizumab in Secondary Progressive MS

Biogen, 21 Oct 2015

Accessed on 27 Oct 2015 from http://media.biogen.com/press-release/corporate/biogen-reports-top-line-results-phase-3-study-evaluating-natalizumab-seconda.

Duration:

Up to 96 weeks (to measure disability progression); after this point, participants can enroll in a 2-year open-label extension (to evaluate safety profile)

(145)

A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis (ASCEND in SPMS)

ClinicalTrials.gov, 12 Sep 2013

Accessed on 6 Feb 2014 from http://clinicaltrials.gov/show/NCT01416181.

Status/Outcome:

The trial did not achieve its primary or secondary endpoints, but natalizumab was associated with an improvement in upper limb function (press release, October 2015)

(296)

Biogen Reports Top-Line Results from Phase 3 Study Evaluating Natalizumab in Secondary Progressive MS

Biogen, 21 Oct 2015

Accessed on 27 Oct 2015 from http://media.biogen.com/press-release/corporate/biogen-reports-top-line-results-phase-3-study-evaluating-natalizumab-seconda.

Trial name:

Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) (publ 2006; additional analyses publ 2011, 2013-2015; press releases, 2013, 2014)

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

(58)

Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis.

Phillips TJ, Giovannoni G, Lublin FD, O'Connor PW, Polman CH, Willoughby E, Aschenbach W, Pace A, Hyde R, Munschauer FE

Mult Scler. 2011 Aug; 17(8):970-9. Epub 2011 Mar 18. PMID: 21421809. Abstract

(59)

Clinical effects of natalizumab on multiple sclerosis appear early in treatment course.

Kappos L, O'Connor PW, Polman CH, Vermersch P, Wiendl H, Pace A, Zhang A, Hotermans C

J Neurol. 2013 Jan 5. Epub 2013 Jan 05. PMID: 23292204. Abstract

(118)

New TYSABRI® data show earlier treatment and longer-term use result in significant reductions in MS disease activity

Biogen Idec, 3 Oct 2013

Accessed on 4 Oct 2013 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1861119.

(178)

New TYSABRI® analysis at AAN annual meeting shows improved walking speed in significant number of MS patients

Biogen Idec, 1 May 2014

Accessed on 15 May 2014 from https://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2322&M=NewsV2&PID=61997.

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

(295)

Natalizumab reduces relapse clinical severity and improves relapse recovery in MS.

Lublin FD, Cutter G, Giovannoni G, Pace A, Campbell NR, Belachew S

Mult Scler Relat Disord. 2014 Nov; 3(6):705-11. Epub 2014 Sep 06. PMID: 25891549. Abstract

Phase:

Phase III trial

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

Study Design:

Industry-sponsored, multinational, randomized, placebo-controlled trial to study the efficacy and safety of natalizumab (300 mg, intravenous infusion every 4 weeks), with the primary endpoint at one year being the rate of clinical relapse and the primary endpoint at two years the cumulative probability of sustained progression of disability, measured by the Expanded Disability Status Scale (EDSS) score

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

Disease Stage:

RRMS

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

Enrollment/Number of Patients:

942

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

Duration:

More than 2 years

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

Status/Outcome:

Natalizumab reduced the rate of clinical relapse by 68% at one year, the risk of sustained progression of disabilty by 42% over two years, and the accumulation of lesions over two years by 83%

(5)

A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips TJ, Lublin FD, Giovannoni G, Wajgt A, et al.

N Engl J Med. 2006 Mar 2; 354(9):899-910. PMID: 16510744. Abstract

; posthoc analysis showed that natalizumab increased the cumulative probability of improvement in EDSS scores (which correlated with quality of life measurements) by 69%

(58)

Phillips TJ, Giovannoni G, Lublin FD, O'Connor PW, Polman CH, Willoughby E, Aschenbach W, Pace A, Hyde R, Munschauer FE

Mult Scler. 2011 Aug; 17(8):970-9. Epub 2011 Mar 18. PMID: 21421809. Abstract

; additional analysis showed that natalizumab rapidly reduced the annualized relapse rate (within 3 months) overall (0.30 versus 0.71 for placebo), even in patients with highly active disease (0.30 versus 0.94)

(59)

Clinical effects of natalizumab on multiple sclerosis appear early in treatment course.

Kappos L, O'Connor PW, Polman CH, Vermersch P, Wiendl H, Pace A, Zhang A, Hotermans C

J Neurol. 2013 Jan 5. Epub 2013 Jan 05. PMID: 23292204. Abstract

; posthoc analysis showed that the drug increased the probability of a lack of evident disease activity (clinically or detected by MRI) in all individuals, but this effect was greater in individuals with an EDSS score <3.0 versus those with a score ≥3.0 at baseline; additional posthoc analysis showed that natalizumab reduced the severity of relapses

(118)

New TYSABRI® data show earlier treatment and longer-term use result in significant reductions in MS disease activity

Biogen Idec, 3 Oct 2013

Accessed on 4 Oct 2013 from http://www.biogenidec.com/press_release_details.aspx?ID=5981&ReqId=1861119.

; additional posthoc analysis showed that at 2 years, natalizumab increased the proportion of participants with confirmed improvement in walking speed relative to placebo

(178)

New TYSABRI® analysis at AAN annual meeting shows improved walking speed in significant number of MS patients

Biogen Idec, 1 May 2014

Accessed on 15 May 2014 from https://www.biogenidec.com/press_release_details.aspx?ID=14712&Action=1&NewsId=2322&M=NewsV2&PID=61997.

; retrospective analysis of AFFIRM (natalizumab), SENTINEL (natalizumab and interferon beta-1a), and IMPACT (interferon beta-1a) trial data showed that 20% to 25% decreases in speed in the timed 25-foot walk correspond to clinically-meaningful reductions in physical component summary scores

(215)

The Clinical Meaning of Walking Speed as Measured by the Timed 25-Foot Walk in Patients With Multiple Sclerosis.

Cohen JA, Krishnan AV, Goodman AD, Potts J, Wang P, Havrdova E, Polman C, Rudick RA

JAMA Neurol. 2014 Sep 1. PMID: 25178496. Abstract

; >20% of participants exhibited loss of visual function, especially low-contrast visual acuity, during AFFIRM; such loss occurred even in individuals without worsening EDSS scores

(227)

Vision in a Phase 3 Trial of Natalizumab for Multiple Sclerosis: Relation to Disability and Quality of Life.

Chahin S, Balcer LJ, Miller DM, Zhang A, Galetta SL

J Neuroophthalmol. 2014 Nov 3. PMID: 25370598. Abstract

; retrospective analysis of treated versus control individuals showed that natalizumab was associated with an increase in the proportion of individuals who exhibited ≥20% improvement in timed 25-foot walk speed at year 2

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

; posthoc analysis showed that natalizumab decreased relapse severity (with a mean increase in the EDSS score of 0.77 for the natalizumab group and 1.09 for the placebo group at relapse) and improved recovery from relapse-associated disability, as measured by changes in the EDSS score

(295)

Natalizumab reduces relapse clinical severity and improves relapse recovery in MS.

Lublin FD, Cutter G, Giovannoni G, Pace A, Campbell NR, Belachew S

Mult Scler Relat Disord. 2014 Nov; 3(6):705-11. Epub 2014 Sep 06. PMID: 25891549. Abstract

Trial name:

Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) (publ 2006)

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Phase:

Phase III trial

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Study Design:

Industry-sponsored, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to determine if natalizumab (300 mg intravenously every 4 weeks) together with interferon beta-1a (30 microg intramuscularly every week) is more effective than interferon beta-1a alone in reducing breakthrough disease activity in patients who had received interferon beta-1a treatment for at least 12 months before randomization in study (with at least one relapse in the 12 months before randomization), with the rate of clinical relapse at 1 year and the cumulative probabilty of disability progression at 2 years the primary end points

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Disease Stage:

RRMS

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Enrollment/Number of Patients:

1171, with 1003 completing the study

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Duration:

2 years

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

Status/Outcome:

Combination therapy was associated with a 23% cumulative probability of sustained disability progression at 2 years versus 29% with interferon beta-1a alone; combination therapy reduced the risk of sustained disability progression by 24% and reduced the annualized rate of relapse by 54% (at 1 year) and 55% (at 2 years) as compared to interferon beta-1a alone; trial was stopped 1 month early because of two cases of progressive multifocal leukoencephalopathy, one of which was fatal

(13)

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, Lublin FD, Weinstock-Guttman B, Wynn DR, Lynn F, et al.

N Engl J Med. 2006 Mar 2; 354(9):911-23. PMID: 16510745. Abstract

(215)

The Clinical Meaning of Walking Speed as Measured by the Timed 25-Foot Walk in Patients With Multiple Sclerosis.

Cohen JA, Krishnan AV, Goodman AD, Potts J, Wang P, Havrdova E, Polman C, Rudick RA

JAMA Neurol. 2014 Sep 1. PMID: 25178496. Abstract

Trial name:

Miller et al., N. Engl. J. Med., Jan 2003 trial

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

Phase:

Phase II trial

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

(57)

Impact of natalizumab on ambulatory improvement in secondary progressive and disabled relapsing-remitting multiple sclerosis.

Cadavid D, Jurgensen S, Lee S

PLoS One. 2013; 8(1):e53297. Epub 2013 Jan 04. PMID: 23308186. Abstract

Study Design:

Company-sponsored, multinational, randomized, placebo-controlled trial to test the efficacy of natalizumab (3 mg or 6 mg per kg of body weight every 28 days, by intravenous infusion) in reducing the number of new gadolinium-enhancing brain lesions (primary end point)

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

Disease Stage:

RRMS or SPMS

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

Enrollment/Number of Patients:

213

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

Duration:

6 months

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

Status/Outcome:

Drug reduced the mean number of new inflammatory brain lesions per patient [such that there were 0.7 (3 mg dose) and 1.1 (6 mg dose) versus 9.6 (placebo)] and reduced the number of relapses

(11)

A controlled trial of natalizumab for relapsing multiple sclerosis.

Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GPA, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O'Connor PW, et al.

N Engl J Med. 2003 Jan 2; 348(1):15-23. PMID: 12510038. Abstract

Trial name:

Tubridy et al., Neurology, Aug 1999 trial

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Phase:

Phase II trial

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Study Design:

Randomized, double-blind, placebo-controlled trial to study the effect of natalizumab (two intravenous infusions 4 weeks apart) on brain lesions (followed up for 24 weeks), as measured by MRI

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Disease Stage:

RRMS and SPMS

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Enrollment/Number of Patients:

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Duration:

28 weeks

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Status/Outcome:

Drug was associated with fewer new active lesions per patient (mean 1.8 versus 3.6 for placebo) in the first 12 weeks of followup, but no difference was seen in the second 12 weeks

(12)

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, Hughes RA, Palace J, Sharrack B, Swingler R, et al.

Neurology. 1999 Aug 11; 53(3):466-72. PMID: 10449105. Abstract

Trial name:

Sheremata et al., Neurology, Mar 1999 trial (publ 1999)

(16)

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M

Neurology. 1999 Mar 23; 52(5):1072-4. PMID: 10102433. Abstract

Phase:

Phase I trial

(16)

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M

Neurology. 1999 Mar 23; 52(5):1072-4. PMID: 10102433. Abstract

Study Design:

Randomized, placebo-controlled, five-level dose escalation study to examine the safety, tolerability, and pharmacokinetics of a single intravenous dose of natalizumab (0.03 to 3.0 mg per kg)

(16)

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M

Neurology. 1999 Mar 23; 52(5):1072-4. PMID: 10102433. Abstract

Disease Stage:

RRMS and SPMS

(16)

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M

Neurology. 1999 Mar 23; 52(5):1072-4. PMID: 10102433. Abstract

Enrollment/Number of Patients:

(16)

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M

Neurology. 1999 Mar 23; 52(5):1072-4. PMID: 10102433. Abstract

Duration:

8 weeks

(16)

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M

Neurology. 1999 Mar 23; 52(5):1072-4. PMID: 10102433. Abstract

Status/Outcome:

All doses were found to be safe and serum concentrations of drug (after infusion of 1 to 3 mg per kg) were detectable for 3 to 8 weeks

(16)

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M

Neurology. 1999 Mar 23; 52(5):1072-4. PMID: 10102433. Abstract

Head-to-Head Trials:

Trial name:

Barbin et al., Neurology, January 2016 study

(314)

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study.

Barbin L, Rousseau C, Jousset N, Casey R, Debouverie M, Vukusic S, De Sèze J, Brassat D, Wiertlewski S, Brochet B, et al.

Neurology. 2016 Jan 29. PMID: 26826205. Abstract

Phase:

Observational study

(314)

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study.

Barbin L, Rousseau C, Jousset N, Casey R, Debouverie M, Vukusic S, De Sèze J, Brassat D, Wiertlewski S, Brochet B, et al.

Neurology. 2016 Jan 29. PMID: 26826205. Abstract

Study Design:

Multicenter, observational, French study to compare the effects of natalizumab and fingolimod on relapses and MRI outcomes, with statistical analysis done using both logistic regression and propensity scores

(314)

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study.

Barbin L, Rousseau C, Jousset N, Casey R, Debouverie M, Vukusic S, De Sèze J, Brassat D, Wiertlewski S, Brochet B, et al.

Neurology. 2016 Jan 29. PMID: 26826205. Abstract

Disease Stage:

RRMS

(314)

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study.

Barbin L, Rousseau C, Jousset N, Casey R, Debouverie M, Vukusic S, De Sèze J, Brassat D, Wiertlewski S, Brochet B, et al.

Neurology. 2016 Jan 29. PMID: 26826205. Abstract

Enrollment/Number of Patients:

629 (326 treated with natalizumab and 303 with fingolimod)

(314)

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study.

Barbin L, Rousseau C, Jousset N, Casey R, Debouverie M, Vukusic S, De Sèze J, Brassat D, Wiertlewski S, Brochet B, et al.

Neurology. 2016 Jan 29. PMID: 26826205. Abstract

Duration:

2 years

(314)

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study.

Barbin L, Rousseau C, Jousset N, Casey R, Debouverie M, Vukusic S, De Sèze J, Brassat D, Wiertlewski S, Brochet B, et al.

Neurology. 2016 Jan 29. PMID: 26826205. Abstract

Status/Outcome:

The group receiving natalizumab had a lower proportion of participants with ≥1 relapse than the group receiving fingolimod at year 1 (confounder-adjusted proportion, 21.1% versus 30.4%) and year 2 (30.9% versus 41.7%) as well as a lower proportion with new T2 and gadolinium-enhancing lesions at both 1 and 2 years

(314)

Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study.

Barbin L, Rousseau C, Jousset N, Casey R, Debouverie M, Vukusic S, De Sèze J, Brassat D, Wiertlewski S, Brochet B, et al.

Neurology. 2016 Jan 29. PMID: 26826205. Abstract

Trial name:

Zecca et al., BMC Neurol., February 2014 study

(153)

Treatment satisfaction, adherence and behavioral assessment in patients de - escalating from natalizumab to interferon beta.

Zecca C, Riccitelli GC, Calabrese P, Pravatà E, Candrian U, Guttmann CRG, Gobbi C

BMC Neurol. 2014; 14(1):38. Epub 2014 Feb 28. PMID: 24576156. Abstract

Phase:

Post-marketing study

(153)

Treatment satisfaction, adherence and behavioral assessment in patients de - escalating from natalizumab to interferon beta.

Zecca C, Riccitelli GC, Calabrese P, Pravatà E, Candrian U, Guttmann CRG, Gobbi C

BMC Neurol. 2014; 14(1):38. Epub 2014 Feb 28. PMID: 24576156. Abstract

Study Design:

Prospective, randomized, rater-blinded, parallel-group study to examine treatment satisfaction in individuals who had been treated with intravenous natalizumab (300 mg monthly) for at least 12 months (and had increased risk or fear of progressive multifocal leukoencephalopathy), who were then randomly assigned to either subcutaneous interferon beta-1b (250 microg every other day) or continued natalizumab treatment

(153)

Treatment satisfaction, adherence and behavioral assessment in patients de - escalating from natalizumab to interferon beta.

Zecca C, Riccitelli GC, Calabrese P, Pravatà E, Candrian U, Guttmann CRG, Gobbi C

BMC Neurol. 2014; 14(1):38. Epub 2014 Feb 28. PMID: 24576156. Abstract

Disease Stage:

RRMS

(153)

Treatment satisfaction, adherence and behavioral assessment in patients de - escalating from natalizumab to interferon beta.

Zecca C, Riccitelli GC, Calabrese P, Pravatà E, Candrian U, Guttmann CRG, Gobbi C

BMC Neurol. 2014; 14(1):38. Epub 2014 Feb 28. PMID: 24576156. Abstract

Enrollment/Number of Patients:

19, with 17 completing the study

(153)

Treatment satisfaction, adherence and behavioral assessment in patients de - escalating from natalizumab to interferon beta.

Zecca C, Riccitelli GC, Calabrese P, Pravatà E, Candrian U, Guttmann CRG, Gobbi C

BMC Neurol. 2014; 14(1):38. Epub 2014 Feb 28. PMID: 24576156. Abstract

Duration:

1 year

(153)

Treatment satisfaction, adherence and behavioral assessment in patients de - escalating from natalizumab to interferon beta.

Zecca C, Riccitelli GC, Calabrese P, Pravatà E, Candrian U, Guttmann CRG, Gobbi C

BMC Neurol. 2014; 14(1):38. Epub 2014 Feb 28. PMID: 24576156. Abstract

Status/Outcome:

Switching from natalizumab to interferon beta-1b was well accepted and tolerated by most individuals, and was associated with stable cognitive and fatigue measures

(153)

Treatment satisfaction, adherence and behavioral assessment in patients de - escalating from natalizumab to interferon beta.

Zecca C, Riccitelli GC, Calabrese P, Pravatà E, Candrian U, Guttmann CRG, Gobbi C

BMC Neurol. 2014; 14(1):38. Epub 2014 Feb 28. PMID: 24576156. Abstract

Trial name:

Oreja-Guevara et al., BMC Neurol., September 2012 study

(86)

TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.

Oreja-Guevara C, Ramos-Cejudo J, Stark Aroeira L, Chamorro B, Diez-Tejedor E

BMC Neurol. 2012; 12:95. Epub 2012 Sep 18. PMID: 22989378. Abstract

Phase:

Observational study

(86)

TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.

Oreja-Guevara C, Ramos-Cejudo J, Stark Aroeira L, Chamorro B, Diez-Tejedor E

BMC Neurol. 2012; 12:95. Epub 2012 Sep 18. PMID: 22989378. Abstract

Study Design:

Cross-sectional, observational study to compare the Th2/Th1 cytokine profile after treatment with glatiramer acetate versus natalizumab; serum levels of Th1 and Th2 cytokines were determined by flow cytometry

(86)

TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.

Oreja-Guevara C, Ramos-Cejudo J, Stark Aroeira L, Chamorro B, Diez-Tejedor E

BMC Neurol. 2012; 12:95. Epub 2012 Sep 18. PMID: 22989378. Abstract

Disease Stage:

RRMS

(86)

TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.

Oreja-Guevara C, Ramos-Cejudo J, Stark Aroeira L, Chamorro B, Diez-Tejedor E

BMC Neurol. 2012; 12:95. Epub 2012 Sep 18. PMID: 22989378. Abstract

Enrollment/Number of Patients:

23 (12 patients treated with glatiramer acetate and 11 with natalizumab)

(86)

TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.

Oreja-Guevara C, Ramos-Cejudo J, Stark Aroeira L, Chamorro B, Diez-Tejedor E

BMC Neurol. 2012; 12:95. Epub 2012 Sep 18. PMID: 22989378. Abstract

Duration:

1 year

(86)

TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.

Oreja-Guevara C, Ramos-Cejudo J, Stark Aroeira L, Chamorro B, Diez-Tejedor E

BMC Neurol. 2012; 12:95. Epub 2012 Sep 18. PMID: 22989378. Abstract

Status/Outcome:

Patients treated with natalizumab exhibited higher levels of interleukin 6 (IL-6), monocyte chemotactic protein, and granulocyte macrophage colony stimulating factor, and a trend for higher IL-12p70, IL-1b, tumor necrosis factor-alpha, and interferon-gamma as compared with those treated with glatiramer acetate, whereas treatment with natalizumab reduced cytokine ratios that serve as markers of the Th2/Th1 ratio as compared with glatiramer acetate; the results suggest that glatiramer acetate supports a better Th2-biased anti-inflammatory response than does natalizumab

(86)

TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab.

Oreja-Guevara C, Ramos-Cejudo J, Stark Aroeira L, Chamorro B, Diez-Tejedor E

BMC Neurol. 2012; 12:95. Epub 2012 Sep 18. PMID: 22989378. Abstract

Trial name:

Rinaldi et al., Mult. Scler., May 2012 trial

(24)

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P

Mult Scler. 2012 May 8. PMID: 22570359. Abstract

Phase:

Postmarketing

(24)

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P

Mult Scler. 2012 May 8. PMID: 22570359. Abstract

Study Design:

Prospective study to determine the efficacy of natalizumab versus interferon beta-1a or glatiramer acetate in reducing the accumulation of new cortical lesions

(24)

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P

Mult Scler. 2012 May 8. PMID: 22570359. Abstract

Disease Stage:

RRMS

(24)

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P

Mult Scler. 2012 May 8. PMID: 22570359. Abstract

Enrollment/Number of Patients:

120

(24)

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P

Mult Scler. 2012 May 8. PMID: 22570359. Abstract

Duration:

2 years

(24)

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P

Mult Scler. 2012 May 8. PMID: 22570359. Abstract

Status/Outcome:

Natalizumab reduced the accumulation of new cortical lesions and the progression of cortical atrophy as compared to interferon beta-1a, glatiramer acetate, or no treatment

(24)

Natalizumab strongly suppresses cortical pathology in relapsing-remitting multiple sclerosis.

Rinaldi F, Calabrese M, Seppi D, Puthenparampil M, Perini P, Gallo P

Mult Scler. 2012 May 8. PMID: 22570359. Abstract

Other Trials:

Trial name:

Koch-Henriksen et al., Mult. Scler., April 2016 study

(328)

A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod.

Koch-Henriksen N, Magyari M, Sellebjerg F, Sørensen P S

Mult Scler. 2016 Apr 7. Epub 1969 Dec 31. PMID: 27055806. Abstract

Phase:

Observational/open-label study

(328)

A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod.

Koch-Henriksen N, Magyari M, Sellebjerg F, Sørensen P S

Mult Scler. 2016 Apr 7. Epub 1969 Dec 31. PMID: 27055806. Abstract

Study Design:

Real-life observational study in Denmark to compare clinical disease activity between individuals treated with natalizumab versus fingolimod; individuals who began treatment either of these drug as their first second-line treatment between July 2011 and March 2015 were prospectively recorded in the Danish MS Treatment Register and the two groups were 1:1 propensity score matched

(328)

A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod.

Koch-Henriksen N, Magyari M, Sellebjerg F, Sørensen P S

Mult Scler. 2016 Apr 7. Epub 1969 Dec 31. PMID: 27055806. Abstract

Disease Stage:

RRMS

(328)

A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod.

Koch-Henriksen N, Magyari M, Sellebjerg F, Sørensen P S

Mult Scler. 2016 Apr 7. Epub 1969 Dec 31. PMID: 27055806. Abstract

Enrollment/Number of Patients:

928 (464 in each group) after propensity score matching

(328)

A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod.

Koch-Henriksen N, Magyari M, Sellebjerg F, Sørensen P S

Mult Scler. 2016 Apr 7. Epub 1969 Dec 31. PMID: 27055806. Abstract

Duration:

N/A

(328)

A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod.

Koch-Henriksen N, Magyari M, Sellebjerg F, Sørensen P S

Mult Scler. 2016 Apr 7. Epub 1969 Dec 31. PMID: 27055806. Abstract

Status/Outcome:

Differences in clinical disease activity were not found between the two treatment arms: for natalizumab, the annualized relapse rate (ARR) was 0.296 and the mean time to first relapse was 2.55 years; for fingolimod, the ARR was 0.307 and the mean time to first relapse was 2.56 years; Expanded Disability Status Scale score change did not differ between the groups

(328)

A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod.

Koch-Henriksen N, Magyari M, Sellebjerg F, Sørensen P S

Mult Scler. 2016 Apr 7. Epub 1969 Dec 31. PMID: 27055806. Abstract

Trial name:

Alping et al., Ann. Neurol., March 2016 study

(326)

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, Axelsson M, Malmeström C, Fink K, Lycke J, et al.

Ann Neurol. 2016 Mar 31. PMID: 27038238. Abstract

Phase:

Observational/open-label study

(326)

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, Axelsson M, Malmeström C, Fink K, Lycke J, et al.

Ann Neurol. 2016 Mar 31. PMID: 27038238. Abstract

Study Design:

Observational study to compare the outcomes for individuals switching, because of positive anti-JC virus antibody status, from natalizumab to either rituximab or fingolimod at three Swidish centers (which had different preferences for rituximab and fingolimod)

(326)

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, Axelsson M, Malmeström C, Fink K, Lycke J, et al.

Ann Neurol. 2016 Mar 31. PMID: 27038238. Abstract

Disease Stage:

RRMS

(326)

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, Axelsson M, Malmeström C, Fink K, Lycke J, et al.

Ann Neurol. 2016 Mar 31. PMID: 27038238. Abstract

Enrollment/Number of Patients:

256 (previously stable on natalizumab), with 55% switching to fingolimod

(326)

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, Axelsson M, Malmeström C, Fink K, Lycke J, et al.

Ann Neurol. 2016 Mar 31. PMID: 27038238. Abstract

Duration:

1.5 years after natalizumab cessation

(326)

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, Axelsson M, Malmeström C, Fink K, Lycke J, et al.

Ann Neurol. 2016 Mar 31. PMID: 27038238. Abstract

Status/Outcome:

Clinical relapses were experienced by 1.8% of individuals who switched to rituximab and 17.6% of individuals who switched to fingolimod within 1.5 years of natalizumab cessation

(326)

Rituximab versus fingolimod after natalizumab in multiple sclerosis patients.

Alping P, Frisell T, Novakova L, Islam-Jakobsson P, Salzer J, Björck A, Axelsson M, Malmeström C, Fink K, Lycke J, et al.

Ann Neurol. 2016 Mar 31. PMID: 27038238. Abstract

Trial name:

Zivadinov et al., Eur. J. Neurol., March 2016 study

(324)

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

Zivadinov R, Hojnacki D, Bergsland N, Kennedy C, Hagemeier J, Melia R, Ramasamy DP, Durfee J, Carl E, Dwyer MG, et al.

Eur J Neurol. 2016 Mar 21. PMID: 26998905. Abstract

Phase:

Observational/open-label study

(324)

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

Zivadinov R, Hojnacki D, Bergsland N, Kennedy C, Hagemeier J, Melia R, Ramasamy DP, Durfee J, Carl E, Dwyer MG, et al.

Eur J Neurol. 2016 Mar 21. PMID: 26998905. Abstract

Study Design:

Observational, prospective study to examine the effects of natalizumab on disability and brain atrophy over the long-term

(324)

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

Zivadinov R, Hojnacki D, Bergsland N, Kennedy C, Hagemeier J, Melia R, Ramasamy DP, Durfee J, Carl E, Dwyer MG, et al.

Eur J Neurol. 2016 Mar 21. PMID: 26998905. Abstract

Disease Stage:

Relapsing MS

(324)

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

Zivadinov R, Hojnacki D, Bergsland N, Kennedy C, Hagemeier J, Melia R, Ramasamy DP, Durfee J, Carl E, Dwyer MG, et al.

Eur J Neurol. 2016 Mar 21. PMID: 26998905. Abstract

Enrollment/Number of Patients:

60; 13 participants received continuous natalizumab (average of 60.6 infusions), 27 continued with some breaks (average of 38.4 infusions), and 20 discontinued (average of 29.5 infusions)

(324)

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

Zivadinov R, Hojnacki D, Bergsland N, Kennedy C, Hagemeier J, Melia R, Ramasamy DP, Durfee J, Carl E, Dwyer MG, et al.

Eur J Neurol. 2016 Mar 21. PMID: 26998905. Abstract

Duration:

5 years of followup

(324)

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

Zivadinov R, Hojnacki D, Bergsland N, Kennedy C, Hagemeier J, Melia R, Ramasamy DP, Durfee J, Carl E, Dwyer MG, et al.

Eur J Neurol. 2016 Mar 21. PMID: 26998905. Abstract

Status/Outcome:

Continuous, longer natalizumab use was associated with a lower relapse rate; disability status was generally stable in the continuous group (with progression occurring in 8% of this group), whereas disability progression occurred in 37% and 35% of participants in the non-continuous and discontinuation groups, respectively; accumulation of lesions and brain atrophy did not differ with respect to natalizumab duration

(324)

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

Zivadinov R, Hojnacki D, Bergsland N, Kennedy C, Hagemeier J, Melia R, Ramasamy DP, Durfee J, Carl E, Dwyer MG, et al.

Eur J Neurol. 2016 Mar 21. PMID: 26998905. Abstract

Trial name:

Zhovtis Ryerson et al., J. Neurol. Neurosurg. Psychiatry, February 2016 study

(319)

Extended interval dosing of natalizumab in multiple sclerosis.

Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, Pandey K, Donnelly S, Pawate S, Bomprezzi R, et al.

J Neurol Neurosurg Psychiatry. 2016 Feb 25. PMID: 26917698. Abstract

Phase:

Retrospective medical record review

(319)

Extended interval dosing of natalizumab in multiple sclerosis.

Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, Pandey K, Donnelly S, Pawate S, Bomprezzi R, et al.

J Neurol Neurosurg Psychiatry. 2016 Feb 25. PMID: 26917698. Abstract

Study Design:

Retrospective review to examine the consequences of reducing the frequency of natalizumab infusion [to potentially reduce the risk of progressive multifocal leukoencephalopathy (PML)]; individuals were classified as receiving one of several extended interval dosing (EID) regimens: early extended dosing (EED; dose every 4 weeks 3 days to 6 weeks 6 days), late extended dosing (LED; dose every 7 weeks to 8 weeks 5 days), or variable extended dosing, which switched between EED and LED, and compared to those receiving standard interval dosing (SID; dose every 4 weeks)

(319)

Extended interval dosing of natalizumab in multiple sclerosis.

Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, Pandey K, Donnelly S, Pawate S, Bomprezzi R, et al.

J Neurol Neurosurg Psychiatry. 2016 Feb 25. PMID: 26917698. Abstract

Disease Stage:

(319)

Extended interval dosing of natalizumab in multiple sclerosis.

Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, Pandey K, Donnelly S, Pawate S, Bomprezzi R, et al.

J Neurol Neurosurg Psychiatry. 2016 Feb 25. PMID: 26917698. Abstract

Enrollment/Number of Patients:

1998 (EED, 249; LED, 274; variable, 382; SID, 1093)

(319)

Extended interval dosing of natalizumab in multiple sclerosis.

Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, Pandey K, Donnelly S, Pawate S, Bomprezzi R, et al.

J Neurol Neurosurg Psychiatry. 2016 Feb 25. PMID: 26917698. Abstract

Duration:

N/A

(319)

Extended interval dosing of natalizumab in multiple sclerosis.

Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, Pandey K, Donnelly S, Pawate S, Bomprezzi R, et al.

J Neurol Neurosurg Psychiatry. 2016 Feb 25. PMID: 26917698. Abstract

Status/Outcome:

The annualized relapse rate (ARR) did not increase as the interval between doses increased, such that ARRs were 0.14 and 0.09 for the SID and EID groups, respectively, and similar proportions of individuals in the SID and EID groups exhibited no evidence of clinical or radiographic disease activity; PML did not occur in the EID group, whereas 4 cases occurred in the SID group

(319)

Extended interval dosing of natalizumab in multiple sclerosis.

Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, Pandey K, Donnelly S, Pawate S, Bomprezzi R, et al.

J Neurol Neurosurg Psychiatry. 2016 Feb 25. PMID: 26917698. Abstract

Trial name:

Plavina et al., J. Clin. Pharmacol., February 2016 study (DELIVER)

(313)

A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis.

Plavina T, Fox EJ, Lucas N, Muralidharan K K, Mikol D

J Clin Pharmacol. 2016 Feb 2. PMID: 26835603. Abstract

Phase:

Observational/open-label study

(313)

A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis.

Plavina T, Fox EJ, Lucas N, Muralidharan K K, Mikol D

J Clin Pharmacol. 2016 Feb 2. PMID: 26835603. Abstract

Study Design:

Randomized, multicenter, open-label study to the compare the pharmacokinetics and pharmacodynamics of 300 mg doses of natalizumab delivered by subcutaneous (SC) injection, intramuscular (IM) injection, or intravenous (IV) infusion

(313)

A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis.

Plavina T, Fox EJ, Lucas N, Muralidharan K K, Mikol D

J Clin Pharmacol. 2016 Feb 2. PMID: 26835603. Abstract

Disease Stage:

RRMS or SPMS; natalizumab-naive

(313)

A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis.

Plavina T, Fox EJ, Lucas N, Muralidharan K K, Mikol D

J Clin Pharmacol. 2016 Feb 2. PMID: 26835603. Abstract

Enrollment/Number of Patients:

(313)

A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis.

Plavina T, Fox EJ, Lucas N, Muralidharan K K, Mikol D

J Clin Pharmacol. 2016 Feb 2. PMID: 26835603. Abstract

Duration:

32 weeks

(313)

A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis.

Plavina T, Fox EJ, Lucas N, Muralidharan K K, Mikol D

J Clin Pharmacol. 2016 Feb 2. PMID: 26835603. Abstract

Status/Outcome:

Peak serum concentrations of natalizumab after SC or IM administration were 40% the level seen after IV administration; mean bioavailability after SC or IM administration was 57.1-71.3% and 48.7%, respectively, relative to IV administration; the pharmacodynamic response and incidence of adverse events and anti-natalizumab antibodies were similar following each type of administration

(313)

A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis.

Plavina T, Fox EJ, Lucas N, Muralidharan K K, Mikol D

J Clin Pharmacol. 2016 Feb 2. PMID: 26835603. Abstract

Trial name:

Weinstock-Guttman et al., J. Neurol. Neurosurg. Psychiatry, January 2016 study

(309)

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.

Weinstock-Guttman B, Hagemeier J, Kavak KS, Saini V, Patrick K, Ramasamy DP, Nadeem M, Carl E, Hojnacki D, Zivadinov R

J Neurol Neurosurg Psychiatry. 2016 Jan 18. PMID: 26780938. Abstract

Phase:

Phase IV study

(309)

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.

Weinstock-Guttman B, Hagemeier J, Kavak KS, Saini V, Patrick K, Ramasamy DP, Nadeem M, Carl E, Hojnacki D, Zivadinov R

J Neurol Neurosurg Psychiatry. 2016 Jan 18. PMID: 26780938. Abstract

Study Design:

Single-blinded, randomized study to compare the effects of immediate versus tapered down natalizumab cessation; those in the immediate discontinuation group stopped natalizumab immediately and began another disease modifying therapy after the last infusion of natalizumab, whereas those in the tapered down group received natalizumab infusions spaced 6 and 8 weeks apart before beginning another therapy

(309)

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.

Weinstock-Guttman B, Hagemeier J, Kavak KS, Saini V, Patrick K, Ramasamy DP, Nadeem M, Carl E, Hojnacki D, Zivadinov R

J Neurol Neurosurg Psychiatry. 2016 Jan 18. PMID: 26780938. Abstract

Disease Stage:

Relapsing MS

(309)

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.

Weinstock-Guttman B, Hagemeier J, Kavak KS, Saini V, Patrick K, Ramasamy DP, Nadeem M, Carl E, Hojnacki D, Zivadinov R

J Neurol Neurosurg Psychiatry. 2016 Jan 18. PMID: 26780938. Abstract

Enrollment/Number of Patients:

50, who had been treated with natalizumab for ≥24 months

(309)

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.

Weinstock-Guttman B, Hagemeier J, Kavak KS, Saini V, Patrick K, Ramasamy DP, Nadeem M, Carl E, Hojnacki D, Zivadinov R

J Neurol Neurosurg Psychiatry. 2016 Jan 18. PMID: 26780938. Abstract

Duration:

12 months

(309)

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.

Weinstock-Guttman B, Hagemeier J, Kavak KS, Saini V, Patrick K, Ramasamy DP, Nadeem M, Carl E, Hojnacki D, Zivadinov R

J Neurol Neurosurg Psychiatry. 2016 Jan 18. PMID: 26780938. Abstract

Status/Outcome:

Discontinuation of natalizumab was associated with new disease activity, but those in the tapered down group exhibited fewer relapses (28 versus 8) and a lower number of new MRI lesions in the 12 months after the last infusion than those in the immediate discontinuation group

(309)

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.

Weinstock-Guttman B, Hagemeier J, Kavak KS, Saini V, Patrick K, Ramasamy DP, Nadeem M, Carl E, Hojnacki D, Zivadinov R

J Neurol Neurosurg Psychiatry. 2016 Jan 18. PMID: 26780938. Abstract

Trial name:

Lo Re et al., Neurol. Ther., December 2015 study

(301)

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

Lo Re M, Capobianco M, Ragonese P, Realmuto S, Malucchi S, Berchialla P, Salemi G, Bertolotto A

Neurol Ther. 2015 Dec; 4(2):147-57. Epub 2015 Dec 08. PMID: 26647006. Abstract

Phase:

Retrospective medical record review

(301)

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

Lo Re M, Capobianco M, Ragonese P, Realmuto S, Malucchi S, Berchialla P, Salemi G, Bertolotto A

Neurol Ther. 2015 Dec; 4(2):147-57. Epub 2015 Dec 08. PMID: 26647006. Abstract

Study Design:

Retrospective review to examine risk factors for and frequency of MS disease reactivation after natalizumab discontinuation in two Italian centers, as well as the effects of disease modifying drugs (DMDs) on reducing the risk of such reactivation

(301)

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

Lo Re M, Capobianco M, Ragonese P, Realmuto S, Malucchi S, Berchialla P, Salemi G, Bertolotto A

Neurol Ther. 2015 Dec; 4(2):147-57. Epub 2015 Dec 08. PMID: 26647006. Abstract

Disease Stage:

(301)

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

Lo Re M, Capobianco M, Ragonese P, Realmuto S, Malucchi S, Berchialla P, Salemi G, Bertolotto A

Neurol Ther. 2015 Dec; 4(2):147-57. Epub 2015 Dec 08. PMID: 26647006. Abstract

Enrollment/Number of Patients:

132

(301)

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

Lo Re M, Capobianco M, Ragonese P, Realmuto S, Malucchi S, Berchialla P, Salemi G, Bertolotto A

Neurol Ther. 2015 Dec; 4(2):147-57. Epub 2015 Dec 08. PMID: 26647006. Abstract

Duration:

≥3 years (2 years before natalizumab treatment and 1 year after natalizumab discontinuation)

(301)

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

Lo Re M, Capobianco M, Ragonese P, Realmuto S, Malucchi S, Berchialla P, Salemi G, Bertolotto A

Neurol Ther. 2015 Dec; 4(2):147-57. Epub 2015 Dec 08. PMID: 26647006. Abstract

Status/Outcome:

Natalizumab discontinuation resulted in disease reactivation (relapses) in 54.4% of these individuals and rebound in 21.2%; reactivation and rebound were correlated with more frequent relapses before natalizumab began, fewer natalizumab infusions, and a longer washout period; after discontinuation, a lack of treatment was associated with more disease activity and rebound than DMDs, and second-line therapies (natalizumab and fingolimod) prevented relapses better than first-line therapies (interferon beta, glatiramer acetate, teriflunomide, and azathioprine) after natalizumab discontinuation

(301)

Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers.

Lo Re M, Capobianco M, Ragonese P, Realmuto S, Malucchi S, Berchialla P, Salemi G, Bertolotto A

Neurol Ther. 2015 Dec; 4(2):147-57. Epub 2015 Dec 08. PMID: 26647006. Abstract

Trial name:

Tramacere et al., Cochrane Database Syst. Rev., September 2015 study

(285)

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G

Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract

Phase:

Retrospective clinical trial analysis

(285)

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G

Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract

Study Design:

Retrospective network meta-analysis to compare the benefits of alemtuzumab, azathioprine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1a (Avonex, Rebif), pegylated interferon beta-1a, interferon beta-1b, laquinimod, mitoxantrone, natalizumab, and teriflunomide; data were extracted from 39 randomized controlled trials that compared one or more of the 15 drugs used as monotherapy to placebo or another drug

(285)

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G

Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract

Disease Stage:

Adults with RRMS

(285)

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G

Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract

Enrollment/Number of Patients:

25,113 individuals were randomized in the studies included in the analyses

(285)

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G

Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract

Duration:

Median duration of studies, 24 months

(285)

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G

Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract

Status/Outcome:

Alemtuzumab was found to be the most protective against relapses during the first 24 months of therapy (moderate quality evidence); the next most protective were found to be mitoxantrone (very low quality evidence), natalizumab (high quality evidence), and fingolimod (moderate quality evidence); mitoxantrone (low quality evidence) was found to be the most effective at delaying disability worsening, followed by alemtuzumab (low quality evidence) and natalizumab (moderate quality evidence); these results must be interpreted conservatively because few trials have been performed for most of the drugs

(285)

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G

Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract

Trial name:

Oliveira et al., Arq. Neuropsiquiatr., September 2015 study

(281)

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers.

de Oliveira E M L, Simm R F, Dasic G, de Morais M M, Perreira S L D A, Callegaro D

Arq Neuropsiquiatr. 2015 Sep; 73(9):736-40. PMID: 26352489. Abstract

Phase:

Observational/open-label study

(281)

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers.

de Oliveira E M L, Simm R F, Dasic G, de Morais M M, Perreira S L D A, Callegaro D

Arq Neuropsiquiatr. 2015 Sep; 73(9):736-40. PMID: 26352489. Abstract

Study Design:

Observational study to examine the safety and effects of natalizumab on annualized relapse rate (ARR) and disability progression in Brazilian individuals with MS

(281)

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers.

de Oliveira E M L, Simm R F, Dasic G, de Morais M M, Perreira S L D A, Callegaro D

Arq Neuropsiquiatr. 2015 Sep; 73(9):736-40. PMID: 26352489. Abstract

Disease Stage:

(281)

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers.

de Oliveira E M L, Simm R F, Dasic G, de Morais M M, Perreira S L D A, Callegaro D

Arq Neuropsiquiatr. 2015 Sep; 73(9):736-40. PMID: 26352489. Abstract

Enrollment/Number of Patients:

(281)

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers.

de Oliveira E M L, Simm R F, Dasic G, de Morais M M, Perreira S L D A, Callegaro D

Arq Neuropsiquiatr. 2015 Sep; 73(9):736-40. PMID: 26352489. Abstract

Duration:

≥12 months

(281)

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers.

de Oliveira E M L, Simm R F, Dasic G, de Morais M M, Perreira S L D A, Callegaro D

Arq Neuropsiquiatr. 2015 Sep; 73(9):736-40. PMID: 26352489. Abstract

Status/Outcome:

Natalizumab reduced the ARR by 91% and improved neurological disability; a larger effect was seen in individuals with an Expanded Disability Status Scale score <3.0 as compared with those with a score ≥3.0

(281)

Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers.

de Oliveira E M L, Simm R F, Dasic G, de Morais M M, Perreira S L D A, Callegaro D

Arq Neuropsiquiatr. 2015 Sep; 73(9):736-40. PMID: 26352489. Abstract

Trial name:

Mattioli et al., PLoS One, July 2015 study

(275)

Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Capra R

PLoS One. 2015; 10(7):e0131803. Epub 2015 Jul 06. PMID: 26148120. Abstract

Phase:

Observational/open-label study

(275)

Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Capra R

PLoS One. 2015; 10(7):e0131803. Epub 2015 Jul 06. PMID: 26148120. Abstract

Study Design:

Observational study to examine the long-term effects of natalizumab on cognition, with assessments at baseline and yearly thereafter; relapse number, Expanded Disability Status Scale (EDSS) score, and effects on cortical atrophy (in a subset of individuals) were also examined

(275)

Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Capra R

PLoS One. 2015; 10(7):e0131803. Epub 2015 Jul 06. PMID: 26148120. Abstract

Disease Stage:

RRMS

(275)

Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Capra R

PLoS One. 2015; 10(7):e0131803. Epub 2015 Jul 06. PMID: 26148120. Abstract

Enrollment/Number of Patients:

(275)

Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Capra R

PLoS One. 2015; 10(7):e0131803. Epub 2015 Jul 06. PMID: 26148120. Abstract

Duration:

3 years

(275)

Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Capra R

PLoS One. 2015; 10(7):e0131803. Epub 2015 Jul 06. PMID: 26148120. Abstract

Status/Outcome:

Natalizumab treatment was associated with improvements in neuropsychological tests of memory, attention, and executive function; at 3 years, there was no change in gray matter volume, but parahippocampal and prefrontal gray matter density was increased; additionally, the annualized relapse rate was reduced at each time point as compared with baseline and the EDSS score was stable

(275)

Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Capra R

PLoS One. 2015; 10(7):e0131803. Epub 2015 Jul 06. PMID: 26148120. Abstract

Trial name:

Johnson et al., CNS Drugs, June 2015 study

(273)

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.

Johnson BH, Bonafede MM, Watson C

CNS Drugs. 2015 Jun 26. PMID: 26113055. Abstract

Phase:

Retrospective claims data analysis

(273)

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.

Johnson BH, Bonafede MM, Watson C

CNS Drugs. 2015 Jun 26. PMID: 26113055. Abstract

Study Design:

Comparison of relapse rates and time to relapse, using US administrative claims data from the Truven Health MarketScan Research Databases and propensity score matching, in individuals treated with platform therapy (interferon beta or glatiramer acetate) or natalizumab

(273)

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.

Johnson BH, Bonafede MM, Watson C

CNS Drugs. 2015 Jun 26. PMID: 26113055. Abstract

Disease Stage:

(273)

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.

Johnson BH, Bonafede MM, Watson C

CNS Drugs. 2015 Jun 26. PMID: 26113055. Abstract

Enrollment/Number of Patients:

882

(273)

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.

Johnson BH, Bonafede MM, Watson C

CNS Drugs. 2015 Jun 26. PMID: 26113055. Abstract

Duration:

12 months of claims data, as well as continuous enrollment for 12 months both before and after the first claim

(273)

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.

Johnson BH, Bonafede MM, Watson C

CNS Drugs. 2015 Jun 26. PMID: 26113055. Abstract

Status/Outcome:

Natalizumab was associated with a reduced rate of relapse (which occurred in 26.5% of individuals in the natalizumab group and 35.5% in the platform group) and greater time to relapse (308 days for the natalizumab group and 283 days for the platform group)

(273)

Platform Therapy Compared with Natalizumab for Multiple Sclerosis: Relapse Rates and Time to Relapse Among Propensity Score-Matched US Patients.

Johnson BH, Bonafede MM, Watson C

CNS Drugs. 2015 Jun 26. PMID: 26113055. Abstract

Trial name:

Klotz et al., BMC Neurol., June 2015 study (ToFingo-Successor)

(271)

Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).

Klotz L, Grützke B, Eveslage M, Deppe M, Gross CC, Kirstein L, Posevitz-Fejfar A, Schneider-Hohendorf T, Schwab N, Meuth SG, et al.

BMC Neurol. 2015; 15:96. Epub 2015 Jun 23. PMID: 26099927. Abstract

Phase:

Observational/open label study

(271)

Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).

Klotz L, Grützke B, Eveslage M, Deppe M, Gross CC, Kirstein L, Posevitz-Fejfar A, Schneider-Hohendorf T, Schwab N, Meuth SG, et al.

BMC Neurol. 2015; 15:96. Epub 2015 Jun 23. PMID: 26099927. Abstract

Study Design:

Investigator-initiated, partly industry-supported, exploratory, open-label, monocentric study to examine immune cell migration and function and disease activity during a switch from natalizumab to fingolimod; participants (who had been receiving natalizumab treatment for ≥12 months) will receive a final natalizumab infusion, after which there will be an 8-week washout period followed by 24 weeks of fingolimod treatment

(271)

Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).

Klotz L, Grützke B, Eveslage M, Deppe M, Gross CC, Kirstein L, Posevitz-Fejfar A, Schneider-Hohendorf T, Schwab N, Meuth SG, et al.

BMC Neurol. 2015; 15:96. Epub 2015 Jun 23. PMID: 26099927. Abstract

Disease Stage:

RRMS

(271)

Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).

Klotz L, Grützke B, Eveslage M, Deppe M, Gross CC, Kirstein L, Posevitz-Fejfar A, Schneider-Hohendorf T, Schwab N, Meuth SG, et al.

BMC Neurol. 2015; 15:96. Epub 2015 Jun 23. PMID: 26099927. Abstract

Enrollment/Number of Patients:

(271)

Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).

Klotz L, Grützke B, Eveslage M, Deppe M, Gross CC, Kirstein L, Posevitz-Fejfar A, Schneider-Hohendorf T, Schwab N, Meuth SG, et al.

BMC Neurol. 2015; 15:96. Epub 2015 Jun 23. PMID: 26099927. Abstract

Duration:

32 weeks

(271)

Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).

Klotz L, Grützke B, Eveslage M, Deppe M, Gross CC, Kirstein L, Posevitz-Fejfar A, Schneider-Hohendorf T, Schwab N, Meuth SG, et al.

BMC Neurol. 2015; 15:96. Epub 2015 Jun 23. PMID: 26099927. Abstract

Status/Outcome:

Recruitment began in April 2014

(271)

Assessment of immune functions and MRI disease activity in relapsing-remitting multiple sclerosis patients switching from natalizumab to fingolimod (ToFingo-Successor).

Klotz L, Grützke B, Eveslage M, Deppe M, Gross CC, Kirstein L, Posevitz-Fejfar A, Schneider-Hohendorf T, Schwab N, Meuth SG, et al.

BMC Neurol. 2015; 15:96. Epub 2015 Jun 23. PMID: 26099927. Abstract

Trial name:

Exploratory Study of the Safety, Tolerability, and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (REFINE) (meeting report, June 2015)

(268)

Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS). (REFINE)

ClinicalTrials.gov, 2 Apr 2015

Accessed on 23 Jun 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01405820.

(269)

Natalizumab SC Similar to IV Every 4 Weeks for MS

Medscape, 22 Jun 2015

Accessed on 23 Jun 2015 from http://www.medscape.com/viewarticle/846795.

Phase:

Phase II study

(268)

Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS). (REFINE)

ClinicalTrials.gov, 2 Apr 2015

Accessed on 23 Jun 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01405820.

Study Design:

Industry-sponsored, randomized, prospective, dose-ranging, double-blind study to compare the effects of giving natalizumab via subcutaneous and intravenous routes [with 300 mg given either subcutaneously or intravenously every 4 or 12 weeks (with matching placebo during the intervening periods in the 12 week dosing groups); 150 mg was also given every 12 weeks by both routes], with the primary outcome measure the cumulative number of combined active lesions; blinding was to dose but not route of administration

(268)

Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS). (REFINE)

ClinicalTrials.gov, 2 Apr 2015

Accessed on 23 Jun 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01405820.

Disease Stage:

RRMS

(268)

Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS). (REFINE)

ClinicalTrials.gov, 2 Apr 2015

Accessed on 23 Jun 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01405820.

Enrollment/Number of Patients:

291; participants had previously received natalizumab for at least 12 months

(268)

Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS). (REFINE)

ClinicalTrials.gov, 2 Apr 2015

Accessed on 23 Jun 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01405820.

Duration:

60 weeks

(268)

Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS). (REFINE)

ClinicalTrials.gov, 2 Apr 2015

Accessed on 23 Jun 2015 from https://www.clinicaltrials.gov/ct2/show/NCT01405820.

Status/Outcome:

Subcutaneous administration every 4 weeks appeared as effective as intravenous administration every 4 weeks (with breakthrough disease activity occurring in the groups receiving drug every 12 weeks); however, Biogen does not plan to attempt to commercialize the subcutaneous product (meeting report, June 2015)

(269)

Natalizumab SC Similar to IV Every 4 Weeks for MS

Medscape, 22 Jun 2015

Accessed on 23 Jun 2015 from http://www.medscape.com/viewarticle/846795.

Trial name:

Kunkel et al., Front. Neurol., May 2015 study

(267)

Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis.

Kunkel A, Fischer M, Faiss J, Dähne D, Köhler W, Faiss JH

Front Neurol. 2015; 6:97. Epub 2015 May 11. PMID: 26029156. Abstract

Phase:

Retrospective, observational/open-label study

(267)

Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis.

Kunkel A, Fischer M, Faiss J, Dähne D, Köhler W, Faiss JH

Front Neurol. 2015; 6:97. Epub 2015 May 11. PMID: 26029156. Abstract

Study Design:

Observational study to examine the effect of natalizumab on depression, attention, and fatigue, with assessments just before natalizumab treatment began and after 1 and 2 years of treatment

(267)

Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis.

Kunkel A, Fischer M, Faiss J, Dähne D, Köhler W, Faiss JH

Front Neurol. 2015; 6:97. Epub 2015 May 11. PMID: 26029156. Abstract

Disease Stage:

RRMS

(267)

Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis.

Kunkel A, Fischer M, Faiss J, Dähne D, Köhler W, Faiss JH

Front Neurol. 2015; 6:97. Epub 2015 May 11. PMID: 26029156. Abstract

Enrollment/Number of Patients:

(267)

Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis.

Kunkel A, Fischer M, Faiss J, Dähne D, Köhler W, Faiss JH

Front Neurol. 2015; 6:97. Epub 2015 May 11. PMID: 26029156. Abstract

Duration:

2 years

(267)

Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis.

Kunkel A, Fischer M, Faiss J, Dähne D, Köhler W, Faiss JH

Front Neurol. 2015; 6:97. Epub 2015 May 11. PMID: 26029156. Abstract

Status/Outcome:

Natalizumab was associated with improvements in certain measures of attention and depression over 1 and 2 years, but not in measures of fatigue

(267)

Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis.

Kunkel A, Fischer M, Faiss J, Dähne D, Köhler W, Faiss JH

Front Neurol. 2015; 6:97. Epub 2015 May 11. PMID: 26029156. Abstract

Trial name:

Zecca et al., Expert Opin. Biol. Ther., May 2015 study

(257)

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

Zecca C, Heldner MR, Kamm CP, Riccitelli GC, Disanto G, Caporro M, Cianfoni A, Pravatà E, Gobbi C

Expert Opin Biol Ther. 2015 May; 15(5):633-40. Epub 2015 Apr 03. PMID: 25840751. Abstract

Phase:

Retrospective data analysis

(257)

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

Zecca C, Heldner MR, Kamm CP, Riccitelli GC, Disanto G, Caporro M, Cianfoni A, Pravatà E, Gobbi C

Expert Opin Biol Ther. 2015 May; 15(5):633-40. Epub 2015 Apr 03. PMID: 25840751. Abstract

Study Design:

Retrospective data collection and comparison of the annualized relapse rate (ARR), disability progression, and the number of new brain and spinal T2 lesions between matched individuals with spinal versus non-spinal MS before and after natalizumab treatment; multivariate regression models were used for the comparisons

(257)

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

Zecca C, Heldner MR, Kamm CP, Riccitelli GC, Disanto G, Caporro M, Cianfoni A, Pravatà E, Gobbi C

Expert Opin Biol Ther. 2015 May; 15(5):633-40. Epub 2015 Apr 03. PMID: 25840751. Abstract

Disease Stage:

(257)

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

Zecca C, Heldner MR, Kamm CP, Riccitelli GC, Disanto G, Caporro M, Cianfoni A, Pravatà E, Gobbi C

Expert Opin Biol Ther. 2015 May; 15(5):633-40. Epub 2015 Apr 03. PMID: 25840751. Abstract

Enrollment/Number of Patients:

136 (68 with spinal and 68 with non-spinal MS)

(257)

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

Zecca C, Heldner MR, Kamm CP, Riccitelli GC, Disanto G, Caporro M, Cianfoni A, Pravatà E, Gobbi C

Expert Opin Biol Ther. 2015 May; 15(5):633-40. Epub 2015 Apr 03. PMID: 25840751. Abstract

Duration:

31.3 (for the spinal MS group) and 32.1 (for the non-spinal MS group) months (mean duration of treatment)

(257)

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

Zecca C, Heldner MR, Kamm CP, Riccitelli GC, Disanto G, Caporro M, Cianfoni A, Pravatà E, Gobbi C

Expert Opin Biol Ther. 2015 May; 15(5):633-40. Epub 2015 Apr 03. PMID: 25840751. Abstract

Status/Outcome:

Natalizumab was associated with similar reductions in ARR and the number of new brain and spinal T2 lesions in the two groups, but only significantly reduced disability progression in spinal MS (disability progression was similarly low in the two groups after treatment initiation, but higher in the spinal group before treatment)

(257)

Natalizumab in spinal multiple sclerosis in a daily clinical setting.

Zecca C, Heldner MR, Kamm CP, Riccitelli GC, Disanto G, Caporro M, Cianfoni A, Pravatà E, Gobbi C

Expert Opin Biol Ther. 2015 May; 15(5):633-40. Epub 2015 Apr 03. PMID: 25840751. Abstract

Trial name:

Spelman et al., Ann. Clin. Transl. Neurol., April 2015 study

(261)

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman T, Kalincik T, Zhang A, Pellegrini F, Wiendl H, Kappos L, Tsvetkova L, Belachew S, Hyde R, Verheul F, et al.

Ann Clin Transl Neurol. 2015 Apr; 2(4):373-87. Epub 2015 Feb 27. PMID: 25909083. Abstract

Phase:

Retrospective data analysis

(261)

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman T, Kalincik T, Zhang A, Pellegrini F, Wiendl H, Kappos L, Tsvetkova L, Belachew S, Hyde R, Verheul F, et al.

Ann Clin Transl Neurol. 2015 Apr; 2(4):373-87. Epub 2015 Feb 27. PMID: 25909083. Abstract

Study Design:

Analysis of data from the MSBase registry and the TYSABRI Observational Program to compare the effects of switching to natalizumab versus switching between interferon beta and glatiramer acetate in individuals who experienced a relapse while on interferon beta or glatiramer acetate; datasets were propensity matched

(261)

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman T, Kalincik T, Zhang A, Pellegrini F, Wiendl H, Kappos L, Tsvetkova L, Belachew S, Hyde R, Verheul F, et al.

Ann Clin Transl Neurol. 2015 Apr; 2(4):373-87. Epub 2015 Feb 27. PMID: 25909083. Abstract

Disease Stage:

Active MS

(261)

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman T, Kalincik T, Zhang A, Pellegrini F, Wiendl H, Kappos L, Tsvetkova L, Belachew S, Hyde R, Verheul F, et al.

Ann Clin Transl Neurol. 2015 Apr; 2(4):373-87. Epub 2015 Feb 27. PMID: 25909083. Abstract

Enrollment/Number of Patients:

869

(261)

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman T, Kalincik T, Zhang A, Pellegrini F, Wiendl H, Kappos L, Tsvetkova L, Belachew S, Hyde R, Verheul F, et al.

Ann Clin Transl Neurol. 2015 Apr; 2(4):373-87. Epub 2015 Feb 27. PMID: 25909083. Abstract

Duration:

Mean followup, 1.7 to 2.2 years

(261)

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman T, Kalincik T, Zhang A, Pellegrini F, Wiendl H, Kappos L, Tsvetkova L, Belachew S, Hyde R, Verheul F, et al.

Ann Clin Transl Neurol. 2015 Apr; 2(4):373-87. Epub 2015 Feb 27. PMID: 25909083. Abstract

Status/Outcome:

Switching to natalizumab was associated with a reduction in annualized relapse rate in the first year by 65 to 75% and a reduction in the risk of confirmed disability progression over the first 24 months by 26% as compared with switching between interferon beta and glatiramer acetate

(261)

Comparative efficacy of switching to natalizumab in active multiple sclerosis.

Spelman T, Kalincik T, Zhang A, Pellegrini F, Wiendl H, Kappos L, Tsvetkova L, Belachew S, Hyde R, Verheul F, et al.

Ann Clin Transl Neurol. 2015 Apr; 2(4):373-87. Epub 2015 Feb 27. PMID: 25909083. Abstract

Trial name:

Frisell et al., Mult. Scler., April 2015 study

(260)

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

Frisell T, Forsberg L, Nordin N, Kiesel C, Alfredsson L, Askling J, Hillert J, Olsson T, Piehl F

Mult Scler. 2015 Apr 28. PMID: 25921036. Abstract

Phase:

Retrospective registry analysis

(260)

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

Frisell T, Forsberg L, Nordin N, Kiesel C, Alfredsson L, Askling J, Hillert J, Olsson T, Piehl F

Mult Scler. 2015 Apr 28. PMID: 25921036. Abstract

Study Design:

Retrospective analysis to examine differences in a real-world setting in baseline characteristics and drug discontinuation among individuals beginning treatment with natalizumab or fingolimod, who registered in a Swedish drug monitoring registry in 2011 to 2013

(260)

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

Frisell T, Forsberg L, Nordin N, Kiesel C, Alfredsson L, Askling J, Hillert J, Olsson T, Piehl F

Mult Scler. 2015 Apr 28. PMID: 25921036. Abstract

Disease Stage:

RRMS

(260)

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

Frisell T, Forsberg L, Nordin N, Kiesel C, Alfredsson L, Askling J, Hillert J, Olsson T, Piehl F

Mult Scler. 2015 Apr 28. PMID: 25921036. Abstract

Enrollment/Number of Patients:

1516 (natalizumab, 640 and fingolimod, 876, with 44% of those on fingolimod previously using natalizumab)

(260)

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

Frisell T, Forsberg L, Nordin N, Kiesel C, Alfredsson L, Askling J, Hillert J, Olsson T, Piehl F

Mult Scler. 2015 Apr 28. PMID: 25921036. Abstract

Duration:

Drug discontinuation at 1 year was monitored

(260)

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

Frisell T, Forsberg L, Nordin N, Kiesel C, Alfredsson L, Askling J, Hillert J, Olsson T, Piehl F

Mult Scler. 2015 Apr 28. PMID: 25921036. Abstract

Status/Outcome:

Those in the fingolimod group were older and more likely to be male than those in the natalizumab group; most [87% (natalizumab), 83% (fingolimod and natalizumab-naïve), and 76% (fingolimod after natalizumab)] continued on treatment after 1 year; individuals on fingolimod discontinued treatment because of adverse events more often than those on natalizumab

(260)

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

Frisell T, Forsberg L, Nordin N, Kiesel C, Alfredsson L, Askling J, Hillert J, Olsson T, Piehl F

Mult Scler. 2015 Apr 28. PMID: 25921036. Abstract

Trial name:

Cobo-Calvo et al., Eur. Neurol., March 2015 study

(254)

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis.

Cobo-Calvo Á, Bau L, Matas E, Romero-Pinel L, Mañé Martínez AM, Majós C, Martínez Yélamos S

Eur Neurol. 2015 Mar 13; 73(3-4):220-229. Epub 2015 Mar 13. PMID: 25792347. Abstract

Phase:

Observational/open-label study

(254)

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis.

Cobo-Calvo Á, Bau L, Matas E, Romero-Pinel L, Mañé Martínez AM, Majós C, Martínez Yélamos S

Eur Neurol. 2015 Mar 13; 73(3-4):220-229. Epub 2015 Mar 13. PMID: 25792347. Abstract

Study Design:

Observational study to examine the effectiveness of natalizumab in highly active RRMS and to determine predictors at baseline of freedom from clinical and radiological disease activity

(254)

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis.

Cobo-Calvo Á, Bau L, Matas E, Romero-Pinel L, Mañé Martínez AM, Majós C, Martínez Yélamos S

Eur Neurol. 2015 Mar 13; 73(3-4):220-229. Epub 2015 Mar 13. PMID: 25792347. Abstract

Disease Stage:

Highly active RRMS

(254)

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis.

Cobo-Calvo Á, Bau L, Matas E, Romero-Pinel L, Mañé Martínez AM, Majós C, Martínez Yélamos S

Eur Neurol. 2015 Mar 13; 73(3-4):220-229. Epub 2015 Mar 13. PMID: 25792347. Abstract

Enrollment/Number of Patients:

70, with 52 completing 2 years

(254)

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis.

Cobo-Calvo Á, Bau L, Matas E, Romero-Pinel L, Mañé Martínez AM, Majós C, Martínez Yélamos S

Eur Neurol. 2015 Mar 13; 73(3-4):220-229. Epub 2015 Mar 13. PMID: 25792347. Abstract

Duration:

Median followup, 2.3 years

(254)

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis.

Cobo-Calvo Á, Bau L, Matas E, Romero-Pinel L, Mañé Martínez AM, Majós C, Martínez Yélamos S

Eur Neurol. 2015 Mar 13; 73(3-4):220-229. Epub 2015 Mar 13. PMID: 25792347. Abstract

Status/Outcome:

Natalizumab was effective in highly active RRMS, such that the annual relapse rate declined from a mean of 2.49 at baseline to 0.47 after 1 year and to 0.34 after 2 years; an Expanded Disability Status Scale score ≤3.0 at baseline correlated with freedom from disease activity

(254)

Effectiveness of Natalizumab in Patients with Highly Active Relapsing Remitting Multiple Sclerosis.

Cobo-Calvo Á, Bau L, Matas E, Romero-Pinel L, Mañé Martínez AM, Majós C, Martínez Yélamos S

Eur Neurol. 2015 Mar 13; 73(3-4):220-229. Epub 2015 Mar 13. PMID: 25792347. Abstract

Trial name:

McQueen et al., J. Manag. Care Spec. Pharm., March 2015 study

(249)

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

McQueen BR, Livingston T, Vollmer T, Corboy J, Buckley B, Allen R R, Nair K, Campbell JD

J Manag Care Spec Pharm. 2015 Mar; 21(3):210-8. PMID: 25726030. Abstract

Phase:

Retrospective database review

(249)

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

McQueen BR, Livingston T, Vollmer T, Corboy J, Buckley B, Allen R R, Nair K, Campbell JD

J Manag Care Spec Pharm. 2015 Mar; 21(3):210-8. PMID: 25726030. Abstract

Study Design:

Retrospective review of the IMS PharMetrics Plus claims database (years 2006 to 2012) to examine the effects of persistent natalizumab use versus the effects of transitioning from persistent to nonpersistent use (and other treatment patterns) on annual relapses and relapse-related costs; persistence was defined as a lack of ≥90 day gaps in therapy

(249)

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

McQueen BR, Livingston T, Vollmer T, Corboy J, Buckley B, Allen R R, Nair K, Campbell JD

J Manag Care Spec Pharm. 2015 Mar; 21(3):210-8. PMID: 25726030. Abstract

Disease Stage:

(249)

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

McQueen BR, Livingston T, Vollmer T, Corboy J, Buckley B, Allen R R, Nair K, Campbell JD

J Manag Care Spec Pharm. 2015 Mar; 21(3):210-8. PMID: 25726030. Abstract

Enrollment/Number of Patients:

2407

(249)

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

McQueen BR, Livingston T, Vollmer T, Corboy J, Buckley B, Allen R R, Nair K, Campbell JD

J Manag Care Spec Pharm. 2015 Mar; 21(3):210-8. PMID: 25726030. Abstract

Duration:

≥2 years of followup

(249)

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

McQueen BR, Livingston T, Vollmer T, Corboy J, Buckley B, Allen R R, Nair K, Campbell JD

J Manag Care Spec Pharm. 2015 Mar; 21(3):210-8. PMID: 25726030. Abstract

Status/Outcome:

Treatment patterns that involved a transition from persistent to nonpersistent natalizumab use were associated with significant increases in annual relapses (mean relapse rate increase, 0.23) and relapse-related costs (mean increase, $1346), whereas those that involved a transition from nonpersistent to persistent use were associated with nonsignificant decreases in these measures

(249)

Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.

McQueen BR, Livingston T, Vollmer T, Corboy J, Buckley B, Allen R R, Nair K, Campbell JD

J Manag Care Spec Pharm. 2015 Mar; 21(3):210-8. PMID: 25726030. Abstract

Trial name:

Kalincik et al., Ann. Neurol., December 2014 study

(239)

Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.

Kalincik T, Horakova D, Spelman T, Jokubaitis V, Trojano M, Lugaresi A, Izquierdo G, Rozsa C, Grammond P, Alroughani R, et al.

Ann Neurol. 2014 Dec 27. PMID: 25546031. Abstract

Phase:

Retrospective data analysis

(239)

Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.

Kalincik T, Horakova D, Spelman T, Jokubaitis V, Trojano M, Lugaresi A, Izquierdo G, Rozsa C, Grammond P, Alroughani R, et al.

Ann Neurol. 2014 Dec 27. PMID: 25546031. Abstract

Study Design:

Analysis of data from the MSBase registry to compare the effects of switching to natalizumab versus fingolimod from interferon beta or glatiramer acetate (with the change in treatment made because of relapses or disability progression in the preceding 6-month period); subpopulations with comparable baseline characteristics were selected by using quasi-randomization with propensity score-based matching

(239)

Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.

Kalincik T, Horakova D, Spelman T, Jokubaitis V, Trojano M, Lugaresi A, Izquierdo G, Rozsa C, Grammond P, Alroughani R, et al.

Ann Neurol. 2014 Dec 27. PMID: 25546031. Abstract

Disease Stage:

RRMS

(239)

Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.

Kalincik T, Horakova D, Spelman T, Jokubaitis V, Trojano M, Lugaresi A, Izquierdo G, Rozsa C, Grammond P, Alroughani R, et al.

Ann Neurol. 2014 Dec 27. PMID: 25546031. Abstract

Enrollment/Number of Patients:

792, with 578 matched (natalizumab, 407; fingolimod, 171)

(239)

Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.

Kalincik T, Horakova D, Spelman T, Jokubaitis V, Trojano M, Lugaresi A, Izquierdo G, Rozsa C, Grammond P, Alroughani R, et al.

Ann Neurol. 2014 Dec 27. PMID: 25546031. Abstract

Duration:

12 months (mean on-study followup)

(239)

Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.

Kalincik T, Horakova D, Spelman T, Jokubaitis V, Trojano M, Lugaresi A, Izquierdo G, Rozsa C, Grammond P, Alroughani R, et al.

Ann Neurol. 2014 Dec 27. PMID: 25546031. Abstract

Status/Outcome:

Switching to natalizumab appeared more effective in decreasing the relapse rate and burden of short term disability than switching to fingolimod, such that the annualized relapse rate changed from 1.5 to 0.2 for natalizumab and from 1.3 to 0.4 for fingolimod and the rate of sustained disability regression was 2.8 times higher for natalizumab versus fingolimod, although the rate of sustained disability progression events was similar

(239)

Switch to natalizumab vs fingolimod in active relapsing-remitting multiple sclerosis.

Kalincik T, Horakova D, Spelman T, Jokubaitis V, Trojano M, Lugaresi A, Izquierdo G, Rozsa C, Grammond P, Alroughani R, et al.

Ann Neurol. 2014 Dec 27. PMID: 25546031. Abstract

Trial name:

Voloshyna et al., Eur. J. Neurol., December 2014 study (TIMER)

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

Phase:

Observational/open-label study

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

Study Design:

Prospective, open-label study to examine whether natalizumab affects ambulation in natalizumab-naive individuals, as measured by timed 25-foot and 100-meter walks at baseline, week 24, and week 48

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

Disease Stage:

RRMS

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

Enrollment/Number of Patients:

215

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

Duration:

48 weeks

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

Status/Outcome:

Natalizumab was associated with increased walking speed in the 25-foot test at week 24 and in the 100-meter test at weeks 24 and 48

(235)

Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.

Voloshyna N, Havrdová E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D

Eur J Neurol. 2014 Dec 15. PMID: 25511792. Abstract

Trial name:

O'Day et al., J. Med. Econ., November 2014 study

(233)

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

O'Day K, Meyer K, Stafkey-Mailey D, Watson C

J Med Econ. 2014 Nov 25:1-22. PMID: 25422991. Abstract

Phase:

Retrospective analysis

(233)

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

O'Day K, Meyer K, Stafkey-Mailey D, Watson C

J Med Econ. 2014 Nov 25:1-22. PMID: 25422991. Abstract

Study Design:

Study to compare the cost-effectiveness of natalizumab versus fingolimod from a Swedish perspective, using data from the AFFIRM and FREEDOMS trials; the model considered costs of drug acquisition, administration and monitoring, and treatment of MS relapses

(233)

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

O'Day K, Meyer K, Stafkey-Mailey D, Watson C

J Med Econ. 2014 Nov 25:1-22. PMID: 25422991. Abstract

Disease Stage:

RRMS and rapidly evolving severe disease

(233)

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

O'Day K, Meyer K, Stafkey-Mailey D, Watson C

J Med Econ. 2014 Nov 25:1-22. PMID: 25422991. Abstract

Enrollment/Number of Patients:

N/A

(233)

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

O'Day K, Meyer K, Stafkey-Mailey D, Watson C

J Med Econ. 2014 Nov 25:1-22. PMID: 25422991. Abstract

Duration:

Costs over a 2-year period were considered

(233)

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

O'Day K, Meyer K, Stafkey-Mailey D, Watson C

J Med Econ. 2014 Nov 25:1-22. PMID: 25422991. Abstract

Status/Outcome:

When all individuals with RRMS were considered, treatment with fingolimod was found to cost less but treatment with natalizumab resulted in more relapses avoided (0.74 versus 0.59); when only individuals with rapidly evolving severe disease were considered, natalizumab dominated fingolimod; natalizumab was found to be cost-effective in >80% of the simulations in both groups of individuals at a willingness-to-pay threshold of 500,000 Swedish kronor per avoided relapse

(233)

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

O'Day K, Meyer K, Stafkey-Mailey D, Watson C

J Med Econ. 2014 Nov 25:1-22. PMID: 25422991. Abstract

Trial name:

Sastre-Garriga et al., Mult. Scler., November 2014 study

(231)

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Sastre-Garriga J, Tur C, Pareto D, Vidal-Jordana A, Auger C, Río J, Huerga E, Tintoré M, Rovira A, Montalban X

Mult Scler. 2014 Nov 12. PMID: 25392330. Abstract

Phase:

Observational/open-label study

(231)

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Sastre-Garriga J, Tur C, Pareto D, Vidal-Jordana A, Auger C, Río J, Huerga E, Tintoré M, Rovira A, Montalban X

Mult Scler. 2014 Nov 12. PMID: 25392330. Abstract

Study Design:

Observational study to examine brain volume changes in individuals treated with natalizumab, with MRI scans performed at baseline and yearly thereafter

(231)

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Sastre-Garriga J, Tur C, Pareto D, Vidal-Jordana A, Auger C, Río J, Huerga E, Tintoré M, Rovira A, Montalban X

Mult Scler. 2014 Nov 12. PMID: 25392330. Abstract

Disease Stage:

(231)

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Sastre-Garriga J, Tur C, Pareto D, Vidal-Jordana A, Auger C, Río J, Huerga E, Tintoré M, Rovira A, Montalban X

Mult Scler. 2014 Nov 12. PMID: 25392330. Abstract

Enrollment/Number of Patients:

(231)

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Sastre-Garriga J, Tur C, Pareto D, Vidal-Jordana A, Auger C, Río J, Huerga E, Tintoré M, Rovira A, Montalban X

Mult Scler. 2014 Nov 12. PMID: 25392330. Abstract

Duration:

3 years

(231)

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Sastre-Garriga J, Tur C, Pareto D, Vidal-Jordana A, Auger C, Río J, Huerga E, Tintoré M, Rovira A, Montalban X

Mult Scler. 2014 Nov 12. PMID: 25392330. Abstract

Status/Outcome:

Gadolinium enhancement (inflammation) present at baseline was linked with greater decreases in brain volume during years 1 and 2 but not during year 3; furthermore, brain volume changes and disability status showed a marginal association at months 12 and 36

(231)

Brain atrophy in natalizumab-treated patients: A 3-year follow-up.

Sastre-Garriga J, Tur C, Pareto D, Vidal-Jordana A, Auger C, Río J, Huerga E, Tintoré M, Rovira A, Montalban X

Mult Scler. 2014 Nov 12. PMID: 25392330. Abstract

Trial name:

Sousa et al., Rev. Neurol., November 2014 study

(225)

The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study.

Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot E N D P E W N S

Rev Neurol. 2014 Nov 1; 59(9):399-406. PMID: 25342053. Abstract

Phase:

Retrospective medical record review

(225)

The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study.

Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot E N D P E W N S

Rev Neurol. 2014 Nov 1; 59(9):399-406. PMID: 25342053. Abstract

Study Design:

Retrospective review of medical data from individuals who were treated with natalizumab in routine clinical practice at 20 centers in Portugal

(225)

The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study.

Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot E N D P E W N S

Rev Neurol. 2014 Nov 1; 59(9):399-406. PMID: 25342053. Abstract

Disease Stage:

RRMS

(225)

The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study.

Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot E N D P E W N S

Rev Neurol. 2014 Nov 1; 59(9):399-406. PMID: 25342053. Abstract

Enrollment/Number of Patients:

383

(225)

The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study.

Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot E N D P E W N S

Rev Neurol. 2014 Nov 1; 59(9):399-406. PMID: 25342053. Abstract

Duration:

Median duration of natalizumab treatment, 12 months

(225)

The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study.

Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot E N D P E W N S

Rev Neurol. 2014 Nov 1; 59(9):399-406. PMID: 25342053. Abstract

Status/Outcome:

Natalizumab reduced the mean annualized relapse rate and Expanded Disability Status scale scores for individuals treated ≥12 months; the treatment was most effective in those who had not received other disease-modifying therapy and in those with less disability

(225)

The efficacy and safety of natalizumab for the treatment of multiple sclerosis in Portugal: a retrospective study.

Sousa L, de Sa J, Sa MJ, Cerqueira JJ, Martins-Silva A, En Nombre Del Portugal Experience With Natalizumab Study Group Snapshot E N D P E W N S

Rev Neurol. 2014 Nov 1; 59(9):399-406. PMID: 25342053. Abstract

Trial name:

Bomprezzi and Pawate, Ther. Adv. Neurol. Disord., September 2014 study

(224)

Extended interval dosing of natalizumab: a two-center, 7-year experience.

Bomprezzi R, Pawate S

Ther Adv Neurol Disord. 2014 Sep; 7(5):227-31. PMID: 25342976. Abstract

Phase:

Retrospective medical record review

(224)

Extended interval dosing of natalizumab: a two-center, 7-year experience.

Bomprezzi R, Pawate S

Ther Adv Neurol Disord. 2014 Sep; 7(5):227-31. PMID: 25342976. Abstract

Study Design:

Retrospective review of medical data from individuals treated with natalizumab, who had the opportunity to switch to extended interval dosing (EID, which is receiving the drug at 6 to 8 week intervals rather than 4 week intervals), a potential method of reducing the risk of progressive multifocal leukoencephalopathy; the aim of this study was to evaluate whether EID was linked with an increase in relapses

(224)

Extended interval dosing of natalizumab: a two-center, 7-year experience.

Bomprezzi R, Pawate S

Ther Adv Neurol Disord. 2014 Sep; 7(5):227-31. PMID: 25342976. Abstract

Disease Stage:

(224)

Extended interval dosing of natalizumab: a two-center, 7-year experience.

Bomprezzi R, Pawate S

Ther Adv Neurol Disord. 2014 Sep; 7(5):227-31. PMID: 25342976. Abstract

Enrollment/Number of Patients:

361 received natalizumab for ≥6 months; of those, 96 received EID natalizumab for ≥6 months

(224)

Extended interval dosing of natalizumab: a two-center, 7-year experience.

Bomprezzi R, Pawate S

Ther Adv Neurol Disord. 2014 Sep; 7(5):227-31. PMID: 25342976. Abstract

Duration:

On average, 22 months (monthly natalizumab) and 20 months (EID natalizumab)

(224)

Extended interval dosing of natalizumab: a two-center, 7-year experience.

Bomprezzi R, Pawate S

Ther Adv Neurol Disord. 2014 Sep; 7(5):227-31. PMID: 25342976. Abstract

Status/Outcome:

Monthly and EID natalizumab therapies were associated with statistically similar relapse rates

(224)

Extended interval dosing of natalizumab: a two-center, 7-year experience.

Bomprezzi R, Pawate S

Ther Adv Neurol Disord. 2014 Sep; 7(5):227-31. PMID: 25342976. Abstract

Trial name:

Gajofatto et al., Eur. Neurol., September 2014 study

(218)

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study.

Gajofatto A, Bianchi M R, Deotto L, Benedetti M D

Eur Neurol. 2014 Sep 6; 72(3-4):173-180. Epub 2014 Sep 06. PMID: 25226868. Abstract

Phase:

Retrospective medical record analysis

(218)

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study.

Gajofatto A, Bianchi M R, Deotto L, Benedetti M D

Eur Neurol. 2014 Sep 6; 72(3-4):173-180. Epub 2014 Sep 06. PMID: 25226868. Abstract

Study Design:

Retrospective analysis of prospectively-collected clinical and MRI data from individuals treated at one hospital in Italy to compare the effects of natalizumab versus fingolimod; individuals treated with natalizumab exhibited more active disease in the pretreatment period

(218)

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study.

Gajofatto A, Bianchi M R, Deotto L, Benedetti M D

Eur Neurol. 2014 Sep 6; 72(3-4):173-180. Epub 2014 Sep 06. PMID: 25226868. Abstract

Disease Stage:

RRMS

(218)

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study.

Gajofatto A, Bianchi M R, Deotto L, Benedetti M D

Eur Neurol. 2014 Sep 6; 72(3-4):173-180. Epub 2014 Sep 06. PMID: 25226868. Abstract

Enrollment/Number of Patients:

87 (57 receiving natalizumab and 30 receiving fingolimod)

(218)

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study.

Gajofatto A, Bianchi M R, Deotto L, Benedetti M D

Eur Neurol. 2014 Sep 6; 72(3-4):173-180. Epub 2014 Sep 06. PMID: 25226868. Abstract

Duration:

23 months (median duration of natalizumab treatment) and 22 months (median duration of fingolimod treatment)

(218)

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study.

Gajofatto A, Bianchi M R, Deotto L, Benedetti M D

Eur Neurol. 2014 Sep 6; 72(3-4):173-180. Epub 2014 Sep 06. PMID: 25226868. Abstract

Status/Outcome:

Individuals treated with natalizumab had a lower risk of relapse than those treated with fingolimod (despite the higher baseline disease activity in those receiving natalizumab), but Expanded Disability Status Scale score and MRI outcomes were similar under the two forms of treatment

(218)

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study.

Gajofatto A, Bianchi M R, Deotto L, Benedetti M D

Eur Neurol. 2014 Sep 6; 72(3-4):173-180. Epub 2014 Sep 06. PMID: 25226868. Abstract

Trial name:

Carvalho et al., Acta. Med. Port., August 2014 study

(217)

Multiple sclerosis treatment with natalizumab: analysis of a hospital-based cohort.

Carvalho A T, Abreu P, Sá M J

Acta Med Port. 2014 Jul-Aug; 27(4):437-43. Epub 2014 Aug 29. PMID: 25203951. Abstract

Phase:

Retrospective medical record review

(217)

Multiple sclerosis treatment with natalizumab: analysis of a hospital-based cohort.

Carvalho A T, Abreu P, Sá M J

Acta Med Port. 2014 Jul-Aug; 27(4):437-43. Epub 2014 Aug 29. PMID: 25203951. Abstract

Study Design:

Retrospective study to examine the effects of natalizumab on the annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) score in a real-world setting

(217)

Multiple sclerosis treatment with natalizumab: analysis of a hospital-based cohort.

Carvalho A T, Abreu P, Sá M J

Acta Med Port. 2014 Jul-Aug; 27(4):437-43. Epub 2014 Aug 29. PMID: 25203951. Abstract

Disease Stage:

(217)

Multiple sclerosis treatment with natalizumab: analysis of a hospital-based cohort.

Carvalho A T, Abreu P, Sá M J

Acta Med Port. 2014 Jul-Aug; 27(4):437-43. Epub 2014 Aug 29. PMID: 25203951. Abstract

Enrollment/Number of Patients:

(217)

Multiple sclerosis treatment with natalizumab: analysis of a hospital-based cohort.

Carvalho A T, Abreu P, Sá M J

Acta Med Port. 2014 Jul-Aug; 27(4):437-43. Epub 2014 Aug 29. PMID: 25203951. Abstract

Duration:

24 months (average time of treatment)

(217)

Multiple sclerosis treatment with natalizumab: analysis of a hospital-based cohort.

Carvalho A T, Abreu P, Sá M J

Acta Med Port. 2014 Jul-Aug; 27(4):437-43. Epub 2014 Aug 29. PMID: 25203951. Abstract

Status/Outcome:

Natalizumab was associated with reductions in the ARR (-1.9) and EDSS score (-0.8)

(217)

Multiple sclerosis treatment with natalizumab: analysis of a hospital-based cohort.

Carvalho A T, Abreu P, Sá M J

Acta Med Port. 2014 Jul-Aug; 27(4):437-43. Epub 2014 Aug 29. PMID: 25203951. Abstract

Trial name:

Ebrahimi et al., Mult. Scler., August 2014 study

(213)

Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K

Mult Scler. 2014 Aug 26. PMID: 25159275. Abstract

Phase:

Observational/open-label study

(213)

Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K

Mult Scler. 2014 Aug 26. PMID: 25159275. Abstract

Study Design:

Prospective, controlled, observational study to assess the effects of fetal exposure to natalizumab during the first trimester; outcomes were compared to those from disease-matched (DM; treated or untreated with other disease-modifying drugs) and healthy control (HC) groups

(213)

Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K

Mult Scler. 2014 Aug 26. PMID: 25159275. Abstract

Disease Stage:

RRMS

(213)

Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K

Mult Scler. 2014 Aug 26. PMID: 25159275. Abstract

Enrollment/Number of Patients:

101 (RRMS, with natalizumab exposure during the first trimester), 78 (DM), 97 (HC)

(213)

Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K

Mult Scler. 2014 Aug 26. PMID: 25159275. Abstract

Duration:

Length of pregnancy

(213)

Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K

Mult Scler. 2014 Aug 26. PMID: 25159275. Abstract

Status/Outcome:

Natalizumab exposure during the first trimester was not associated with increased risk of adverse outcomes relative to risks in the DM group; the rate of major malformations, low birth weight, and premature birth were similar among all three groups, whereas miscarriage rates were higher in the natalizumab and DM groups

(213)

Pregnancy and fetal outcomes following natalizumab exposure in pregnancy. A prospective, controlled observational study.

Ebrahimi N, Herbstritt S, Gold R, Amezcua L, Koren G, Hellwig K

Mult Scler. 2014 Aug 26. PMID: 25159275. Abstract

Trial name:

Glanz et al., Int. J. MS Care, Summer 2014 study

(205)

Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC

Int J MS Care. 2014 Summer; 16(2):68-75. PMID: 25061430. Abstract

Phase:

Observational/open-label study

(205)

Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC

Int J MS Care. 2014 Summer; 16(2):68-75. PMID: 25061430. Abstract

Study Design:

Study to compare patient satisfaction with intramuscular interferon beta-1a, subcutaneous interferon beta-1a, glatiramer acetate, and natalizumab and to compare links between therapy adherence and satisfaction; the Treatment Satisfaction Questionnaire for Medicine and multivariable models were used

(205)

Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC

Int J MS Care. 2014 Summer; 16(2):68-75. PMID: 25061430. Abstract

Disease Stage:

(205)

Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC

Int J MS Care. 2014 Summer; 16(2):68-75. PMID: 25061430. Abstract

Enrollment/Number of Patients:

226

(205)

Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC

Int J MS Care. 2014 Summer; 16(2):68-75. PMID: 25061430. Abstract

Duration:

N/A

(205)

Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC

Int J MS Care. 2014 Summer; 16(2):68-75. PMID: 25061430. Abstract

Status/Outcome:

Overall, the drugs were associated with similar levels of satisfaction; compared to intramuscular interferon beta-1a, natalizumab was associated with more satisfaction with the ability of the drug to treat or prevent MS and was considered more convenient; natalizumab was considered easier to use than either form of interferon beta or glatiramer acetate; intramuscular interferon beta-1a was associated with less satisfaction with ease of planning than the other drugs; and for subcutaneous interferon beta-1a and glatiramer acetate, lower convenience scores were linked with reduced adherence

(205)

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

Glanz BI, Musallam A, Rintell DJ, Chitnis T, Weiner HL, Healy BC

Int J MS Care. 2014 Summer; 16(2):68-75. PMID: 25061430. Abstract

Trial name:

Bergvall et al., J. Med. Econ., July 2014 study

(203)

Bergvall N, Petrilla AA, Karkare SU, Lahoz R, Agashivala N, Pradhan A, Capkun G, Makin C, Balderston McGuiness C, Korn JR

J Med Econ. 2014 Jul 23:1-12. PMID: 25019581. Abstract

Phase:

Retrospective claims data review

(203)

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

Bergvall N, Petrilla AA, Karkare SU, Lahoz R, Agashivala N, Pradhan A, Capkun G, Makin C, Balderston McGuiness C, Korn JR

J Med Econ. 2014 Jul 23:1-12. PMID: 25019581. Abstract

Study Design:

Company-sponsored, retrospective study to compare persistence with and adherence to fingolimod versus glatiramer acetate, interferon, and natalizumab using administrative claims data from the US PharMetrics Plus database

(203)

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

Bergvall N, Petrilla AA, Karkare SU, Lahoz R, Agashivala N, Pradhan A, Capkun G, Makin C, Balderston McGuiness C, Korn JR

J Med Econ. 2014 Jul 23:1-12. PMID: 25019581. Abstract

Disease Stage:

(203)

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

Bergvall N, Petrilla AA, Karkare SU, Lahoz R, Agashivala N, Pradhan A, Capkun G, Makin C, Balderston McGuiness C, Korn JR

J Med Econ. 2014 Jul 23:1-12. PMID: 25019581. Abstract

Enrollment/Number of Patients:

3750 [fingolimod (889), glatiramer acetate (1233), any interferon (1341), natalizumab (287)]

(203)

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

Bergvall N, Petrilla AA, Karkare SU, Lahoz R, Agashivala N, Pradhan A, Capkun G, Makin C, Balderston McGuiness C, Korn JR

J Med Econ. 2014 Jul 23:1-12. PMID: 25019581. Abstract

Duration:

Study included individuals with at least one prescription for or administration of a relevant drug between 1 October 2010 and 30 September 2011

(203)

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

Bergvall N, Petrilla AA, Karkare SU, Lahoz R, Agashivala N, Pradhan A, Capkun G, Makin C, Balderston McGuiness C, Korn JR

J Med Econ. 2014 Jul 23:1-12. PMID: 25019581. Abstract

Status/Outcome:

Drug discontinuation rates were lower for fingolimod (27.9%) versus other therapies [glatiramer acetate (39.5%), interferons (43.7%), natalizumab (39.5%)]; fingolimod was also associated with a lower risk of non-adherence compared to the other therapies

(203)

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis.

Bergvall N, Petrilla AA, Karkare SU, Lahoz R, Agashivala N, Pradhan A, Capkun G, Makin C, Balderston McGuiness C, Korn JR

J Med Econ. 2014 Jul 23:1-12. PMID: 25019581. Abstract

Trial name:

Totaro et al., Int. J. Immunopathol. Pharmacol., July-September 2014 study

(200)

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, et al.

Int J Immunopathol Pharmacol. 2014 Jul-Sep; 27(2):147-54. PMID: 25004826. Abstract

Phase:

Observational/open-label study

(200)

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, et al.

Int J Immunopathol Pharmacol. 2014 Jul-Sep; 27(2):147-54. PMID: 25004826. Abstract

Study Design:

Observational, multicenter study to examine the effects of natalizumab on a variety of parameters in a clinical setting

(200)

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, et al.

Int J Immunopathol Pharmacol. 2014 Jul-Sep; 27(2):147-54. PMID: 25004826. Abstract

Disease Stage:

RRMS

(200)

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, et al.

Int J Immunopathol Pharmacol. 2014 Jul-Sep; 27(2):147-54. PMID: 25004826. Abstract

Enrollment/Number of Patients:

343

(200)

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, et al.

Int J Immunopathol Pharmacol. 2014 Jul-Sep; 27(2):147-54. PMID: 25004826. Abstract

Duration:

Participants were enrolled between April 2007 and November 2010

(200)

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, et al.

Int J Immunopathol Pharmacol. 2014 Jul-Sep; 27(2):147-54. PMID: 25004826. Abstract

Status/Outcome:

Natalizumab was found to be more effective in this clinical practice setting than in pivotal trials; after followup, 68% (cumulative proportion) of participants were free of relapses, 93% were free of Expanded Disability Status Scale progression, 65% were free of combined clinical activity (that is, relapse or disease progression), 77% were free of MRI activity, and 53% were free of any disease activity

(200)

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, et al.

Int J Immunopathol Pharmacol. 2014 Jul-Sep; 27(2):147-54. PMID: 25004826. Abstract

Trial name:

Capobianco et al., Eur. J. Neurol., July 2014 study

(201)

No impact of current therapeutic strategies on disease reactivation after natalizumab discontinuation: a comparative analysis of different approaches during the first year of natalizumab discontinuation.

Capobianco M, di Sapio A, Malentacchi M, Malucchi S, Matta M, Sperli F, Bertolotto A

Eur J Neurol. 2014 Jul 3. PMID: 24995482. Abstract

Phase:

Retrospective medical record review

(201)

Capobianco M, di Sapio A, Malentacchi M, Malucchi S, Matta M, Sperli F, Bertolotto A

Eur J Neurol. 2014 Jul 3. PMID: 24995482. Abstract

Study Design:

Study to examine whether any therapeutic approach that had been used (immunomodulating agents, other first-line therapies, fingolimod, or no treatment) had abolished MS disease recurrence after the discontinuation of natalizumab

(201)

Capobianco M, di Sapio A, Malentacchi M, Malucchi S, Matta M, Sperli F, Bertolotto A

Eur J Neurol. 2014 Jul 3. PMID: 24995482. Abstract

Disease Stage:

(201)

Capobianco M, di Sapio A, Malentacchi M, Malucchi S, Matta M, Sperli F, Bertolotto A

Eur J Neurol. 2014 Jul 3. PMID: 24995482. Abstract

Enrollment/Number of Patients:

(201)

Capobianco M, di Sapio A, Malentacchi M, Malucchi S, Matta M, Sperli F, Bertolotto A

Eur J Neurol. 2014 Jul 3. PMID: 24995482. Abstract

Duration:

First year of natalizumab discontinuation

(201)

Capobianco M, di Sapio A, Malentacchi M, Malucchi S, Matta M, Sperli F, Bertolotto A

Eur J Neurol. 2014 Jul 3. PMID: 24995482. Abstract

Status/Outcome:

Recurrence of disease activity (clinically or assessed by MRI) was similar among all groups (except that no disease reactivation occurred in an individual treated with 6 months with cyclophosphamide), indicating that current therapeutic strategies have no effect on disease reactivation after the discontinuation of natalizumab

(201)

Capobianco M, di Sapio A, Malentacchi M, Malucchi S, Matta M, Sperli F, Bertolotto A

Eur J Neurol. 2014 Jul 3. PMID: 24995482. Abstract

Trial name:

TY-STOP study (meeting report, June 2014; publ June 2014)

(193)

Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Keller DM, Medscape, 12 Jun 2014

Accessed on 19 Jun 2014 from http://www.medscape.com/viewarticle/826643?src=rss#1.

(197)

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

Phase:

Observational/open-label study

(193)

Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Keller DM, Medscape, 12 Jun 2014

Accessed on 19 Jun 2014 from http://www.medscape.com/viewarticle/826643?src=rss#1.

(197)

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

Study Design:

Prospective, multicenter, observational study to examine the effects of natalizumab discontinuation versus continuation after 2 years of monthly treatments (24 doses, 300 mg each); individuals could choose to continue with natalizumab, start treatment with a different disease-modifying therapy, or stop therapy; the mean annualized relapse rate was the primary endpoint

(193)

Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Keller DM, Medscape, 12 Jun 2014

Accessed on 19 Jun 2014 from http://www.medscape.com/viewarticle/826643?src=rss#1.

(197)

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

Disease Stage:

Clinically and radiologically stable RRMS

(193)

Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Keller DM, Medscape, 12 Jun 2014

Accessed on 19 Jun 2014 from http://www.medscape.com/viewarticle/826643?src=rss#1.

(197)

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

Enrollment/Number of Patients:

130

(193)

Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Keller DM, Medscape, 12 Jun 2014

Accessed on 19 Jun 2014 from http://www.medscape.com/viewarticle/826643?src=rss#1.

(197)

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

Duration:

1 year followup (after 2 years of natalizumab treatment)

(193)

Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Keller DM, Medscape, 12 Jun 2014

Accessed on 19 Jun 2014 from http://www.medscape.com/viewarticle/826643?src=rss#1.

(197)

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

Status/Outcome:

Of 124 individuals with complete followup information, 43 continued on natalizumab and 81 interrupted natalizumab treatment

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Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

; both clinical and radiologic MS activity was lower in those continuing with natalizumab as compared with those who switched or quit treatment

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Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study).

Clerico M, Schiavetti I, De Mercanti SF, Piazza F, Gned D, Brescia Morra V, Lanzillo R, Ghezzi A, Bianchi A, Salemi G, et al.

JAMA Neurol. 2014 Jun 30. Epub 1969 Dec 31. PMID: 24977406. Abstract

; the Expanded Disability Status Scale scores were similar between the groups but the annualized relapse rate increased in those who did not continue natalizumab (0.17 in those who continued natalizumab versus 0.75 in those who stopped treatment and 0.56 in those who switched to a different treatment)

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Keller DM, Medscape, 12 Jun 2014

Accessed on 19 Jun 2014 from http://www.medscape.com/viewarticle/826643?src=rss#1.

; 1 case of progressive multifocal leukoencephalopathy occurred in an individual who switched to a different treatment after 28 months of natalizumab

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