Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study.
ABSTRACT To evaluate the efficacy and safety of interferon beta-1b (IFNbeta-1b) in subjects with secondary progressive multiple sclerosis (SPMS).
This 3-year, multicenter, double-blind, placebo-controlled, randomized trial of IFNbeta-1b included 939 subjects from the United States and Canada with SPMS and Expanded Disability Status Scale (EDSS) scores ranging from 3.0 to 6.5. Subjects were randomly assigned to receive either placebo or IFNbeta-1b (250 microg or 160 microg/m2 body surface area), administered subcutaneously every other day. The primary outcome was time to progression by > or =1.0 EDSS point (0.5 point if EDSS score was 6.0 to 6.5 at entry) confirmed at 6 months. Secondary outcomes included mean change in EDSS score from baseline, relapse-related measures, MRI activity, and a standardized neuropsychological function test.
There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNbeta-1b treatment groups. However, IFNbeta-1b treatment resulted in improvement on secondary outcome measures involving clinical relapses, newly active MRI lesions, and accumulated burden of disease on T2-weighted MRI. Effects were similar for both IFNbeta-1b treatment groups. Neutralizing antibodies to IFNbeta-1b were detected in 23% of 250-microg and 32% of 160-microg/m2 recipients, but their presence did not consistently affect clinical or MRI outcomes. IFNbeta-1b was also well tolerated at both doses.
Although no treatment benefit was seen on the time to confirmed progression of disability, relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested, a result consistent with the outcomes of earlier clinical trials.
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ABSTRACT: Antibodies to interferon-beta (IFNb) may occur during treatment with this drug and can be measured at several levels, the totality of antibodies referred to as antidrug antibodies (ADA) or binding antibodies, and in case of interference with the drug activity referred to as neutralizing antibodies (NAB). Antibodies can also interfere with the biological activity of IFNb as measured by pharmacodynamic markers. To get a complete picture of the interference between IFNb as a drug and the ADA, all the 3 above levels need to be considered. Furthermore, the interaction of these biomarkers changes over time with a shift of antibody properties with respect to immunoglobulin subtypes, affinity, and titers of antibodies. In case of persistent NAB, the clinical benefit of IFNb in the treatment of multiple sclerosis is abolished. In this report, the current knowledge on these issues will be reviewed. The data have been presented at a meeting in Coral Gables, Florida on April 18-21, 2012.Journal of Interferon & Cytokine Research 12/2014; 34(12):938-945. DOI:10.1089/jir.2012.0135 · 3.90 Impact Factor