PEGylated Interferon May Boost Efficacy, Reduce Side Effects
Compared with standard therapy using interferon beta-1, PEGylated interferon beta-1 is showing promising results in managing relapsing-remitting multiple sclerosis, offering potential advantages of both improved efficacy and reduced side effects.
That is according to an update on that approach that appears in the current issue of the journal Biologics: Targets and Therapy. Reinhard Reuss, Ph.D., BKH Bayreuth, Bayreuth, Germany, authored the review (Reuss, 2013).
"Current standard immunomodulatory therapy with interferons (IFNs) for relapsing–remitting multiple sclerosis (MS) exhibits proven, but limited, efficacy and increased side effects due to the need of frequent application of the drug," wrote Dr. Reuss.
However, he says that given the relatively small size of the interferon molecule, it may be possible to use a PEGylation process to increase its efficacy while cutting down on side effects.
Essentially, the process involves the covalent addition of at least one molecule of polyethylene glycol (PEG) to interferon, the aim being to increase stability, solubility, half-life, and efficacy. Dr. Reuss points out that PEGylation has been successfully applied to treatments for a number of other diseases, including rheumatoid arthritis, Crohn's disease, and hepatitis C.
Several trials focusing on MS have been carried out, and more are under way, to determine what advantages PEGylated interferon (PEG-IFN) beta-1 may have over standard IFN beta-1 therapy.
One such phase 1 trial showed that PEG-IFN administered subcutaneously at a dose of 125 μm every 2 or 4 weeks might be at least as effective as the current standard therapy. Aiming to find out more, researchers are now conducting a phase 3 placebo-controlled trial evaluating the efficacy of subcutaneous PEG-IFN in cutting down relapse rates in patients with relapsing-remitting MS.
Preliminary data obtained 1 year into the study show that compared with patients administered placebo, those taking PEG-IFN every 2 weeks had 35.6% fewer relapses. In patients taking PEG-IFN every 4 weeks, the reduction in relapses dropped to 27.5%.
Further, Dr. Reuss noted, the number of new or newly enlarging brain MRI hyperintense T2 lesions was reduced by 67% (P < 0.001) in the group taking PEG-IFN every 2 weeks and by 28% (P < 0.001) in the group who took PEG-IFN every 4 weeks.
The most commonly seen adverse effects were redness at the injection site and flulike symptoms. The most serious side effect was infection, which occurred in about 1% of patients in both treatment groups.
Dr. Reuss cautioned that chronic administration of PEGylated proteins may be linked to vacuolation of renal epithelium, which has been documented in animal studies. That issue, along with the relevance of anti-PEG antibodies, needs to be part of phase 4 trials, he says.
Key open questions
- How is it possible to avoid vacuolation of renal epithelium, which appears to be associated with chronic administration of PEGylated proteins?
- What actual advantages—in terms of quality-adjusted life years and cost-effectiveness—does administration of PEGylated interferon beta-1 have compared with use of standard interferon beta-1?
S. Nevit Dilmen, Creative Commons
The author has disclosed no relevant financial interests.