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Comparison of MS trials baseline characteristics

Comparison of MS trials baseline characteristics

Background
The advent of therapies in MS has revolutionized its management. Several treatment options are now available to people with MS. As a consequence, it may become difficult to determine which one is best for a given patient. To make this decision, clear and objective comparisons of treatment characteristics are required. Such comparisons, to be reliable, would require the absence or at least the control of any confounding factor (such as medical history or age of the patient) that may bias the interpretation of clinical benefits or side effects. Patient characteristics at baseline (i.e. prior to treatment) are important confounding factors.
Data display
The below interactive parallel coordinates visualization presents the group-level baseline characteristics of 33 phase III or phase IV randomized controlled clinical trials in RRMS patients. The data were gathered from the articles presenting the main results of each trial respectively. This interactive plot allows you to compare baseline characteristics between trials. Select up to four trial names to enable the comparison.
Mouse over the points and/or lines to reveal the specific trial/group values.

Note: In case of missing data (e.g. FREEDOMS II or PRISMS), the segmented line is interrupted but the points on the following axes (if any) are displayed.


































Interpretation

One should not expect patient populations involved in various trials to be strictly identical. However, it is important to get a sense of how different these groups of patients are at baseline (i.e., before any treatment is taken), before conducting any between-trial comparisons.

Looking across all studies, the typical group of RRMS patients at baseline would have the following characteristics:

  • ~70% women
  • patients of 36 years of age,
  • having experienced ~1.5 relapses during the year before entry in the study,
  • with 1st symptoms of MS having appeared approximately 7 years ago,
  • a disability (EDSS) score of 2.5,
  • the brain images revealing 2 gadolinium-enhanced lesions, a T2 lesion volume of about 9 cm3, and a brain volume of 1500 cm3.
Looking at the range of values for each axis respectively, we notice that most values are concentrated in only a small portion of the total range, which gives us the possibility to clearly identify the "outlying" groups or trials, such as IFNB-Mitox or GLANCE.

Further digging is possible. For instance, let's focus on AFFIRM and CLARITY trials. Differences can be noticed between these trials concerning disease duration (MSdur), patient disability (EDSS) and Gd-enhancing lesion characteristics at baseline. Such differences would have to be accounted for when comparing the outcomes of these two trials.

About Parallel Coordinates

Parallel coordinates are similar in appearance to line charts, but their interpretations are substantially different. In line charts, lines are predominantly used to encode time-series; hence, slopes are key piece of information to extract from these charts. In parallel coordinates, slopes are not meaningful since lines connect series of values, each corresponding with a different variable, using its own range and unit. This is the reason why points were added to the above plot in order to emphasize the values observed on each axis respectively. On the other hand, line chart are 2D plots (x and y), where parallel coordinates are p-dimensional plots (with p, the number of coordinates or variables). The strength of interactive parallel coordinates resides in their ability to bring meaningful multivariate patterns and comparisons to light. Parallel coordinates convey a lot of information in a single plot. It is recommended to start looking at the big picture first, and then drill down to the specific values of each variable (vertical axis) and each profile (line path), thanks to the hovering and clicking options offered by this interactive chart.

Data source

Data source: click here to download the database (csv format)

The data were extracted from the following articles:

  • AFFIRM: "A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis", The New England Journal of Medecine. (Polman et al, 2006)
  • ALLEGRO: "Placebo-Controlled Trial of Oral Laquinimod for Multiple Sclerosis", The New England Journal of Medecine. (Comi et al, 2012)
  • BECOME: "Efficacy of treatment of MS with IFN β -1b or glatiramer acetate by monthly brain MRI in the BECOME study", American Academy of Neurology. (Cadavid et al, 2009)
  • BEYOND: "250 μg or 500 μg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study", Lancet Neurology. (O'Connor et al, 2009)
  • BRAVO: "A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis", Journal of Neurology. (Vollmer at al, 2014)
  • CARE-MS I: "Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS)", poster ECTRIMS 2011. (Fox et al, 2011)
  • CARE-MS II: "Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS II)", poster ECTRIMS 2011. (Fox et al, 2011)
  • CLARITY: "A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis", The New England Journal of Medecine. (Giovannoni et al, 2010)
  • CONFIRM: "Placebo-controlled Phase III study of oral BG-12 or Glatiramer in Multiple Sclerosis", The New England Journal of Medecine. (Fox et al, 2012)
  • CORAL: "Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study", Lancet Neurology. (Filippi et al, 2006)
  • CombiRx: "Randomized study combining interferon and glatiramer acetate in multiple sclerosis", NIH public Access. (Lublin et al, 2013)
  • DEFINE: "Placebo-controlled Phase III study of oral BG-12 for Multiple Sclerosis", The New England Journal of Medecine. (Gold et al, 2012)
  • EVIDENCE: "Randomized, comparative study of interferon beta 1a treatment regimens in MS. The EVIDENCE Trial", American Academy of Neurology. (Panitch et al, 2002)
  • FORTE: "Phase III Dose-Comparison Study of Glatiramer Acetate for Multiple Sclerosis", Annals of Neurology. (Comi et al, 2011)
  • FREEDOMS: "A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis", The New England Journal of Medecine. (Kappos et al, 2010)
  • FREEDOMS II: "Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial", Lancet Neurology. (Calabresi et al, 2014)
  • GA PhIII: "Copolymer 1 reduces relapse rate and improves disability in relapsing remitting multiple sclerosis", American Academy of Neurology. (Johnson et al, 1995)
  • GLANCE: "Results of a phase 2, randomized, double-blind, placebo-controlled study", American Academy of Neurology. (Goodman et al, 2009)
  • IFNB DoseComp: "A randomized, double-blind, dose-comparison study of weekly interferon beta 1a in relapsing MS", American Academy of Neurology. (Clanet et al, 2002)
  • IFNB Iran: "Comparison of Betaferon, Avonex, and Rebif in treatment of relapsing-remitting multiple sclerosis", Acta Neurologica Scandinavica. (Etemadifar et al, 2006)
  • IFNB-GA Italy: "Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing-remitting multiple sclerosis", Multiple Sclerosis Journal. (Calabrese et al, 2012)
  • IFBN-Mitox: "Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial", Journal Neurology Neurosurgery Psychiatry. (Edan et al, 2011)
  • INCOMIN: "Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN)", The Lancet. (Durelli et al, 2002)
  • IVIg PhIII: "Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis", The Lancet. (Fazekas et al, 1997)
  • MSCRG: "A phase III trial of intramuscular recombinant interferon beta as treatment for exacerbating-remitting multiple sclerosis: design and conduct of study and baseline characteristics of patients", Multiple Sclerosis. (Jacobs et al, 1995)
  • OWIMS: "Evidence of interferon b-1a dose response in relapsing-remitting MS. The OWIMS Study", American Academy of Neurology. (OWIMS study group, 1999)
  • PRISMS: "Randomised double-blind placebo-controlled study of interferon beta 1a in relapsing/remitting multiple sclerosis", The Lancet. (PRISMS study group, 1998)
  • REGARD: "Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial", Lancet Neurology. (Mikol et al, 2008)
  • SENTINEL: "Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis", The New England Journal of Medecine. (Rudick et al, 2006)
  • TEMSO: "Randomized Trial of Oral Teriflunomide for Relapsing Multiple Sclerosis", The New England Journal of Medecine. (O'Connor et al, 2011)
  • TOFINGO: "Switching from natalizumab to fingolimod", American Academy of Neurology. (Kappos et al, 2015)
  • TOWER: "Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial", Lancet Neurology. (Confavreux et al, 2014)
  • TRANSFORMS: "Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis", The New England Journal of Medecine. (Cohen et al, 2010)