Lessons from randomised direct comparative trials

Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, and Sackler School of Medicine, Tel-Aviv University, Israel.
Journal of the Neurological Sciences (Impact Factor: 2.47). 03/2009; 277 Suppl 1:S19-24. DOI: 10.1016/S0022-510X(09)70007-3
Source: PubMed


For over a decade, four immunomodulatory therapies have been available for the treatment of relapsing remitting multiple sclerosis. However, few direct comparative data were available to facilitate the choice of treatment. This choice has been influenced by the perception that interferon-beta preparations have greater efficacy than glatiramer acetate, due to apparently more rapid and robust reduction of gadolinium-enhancing lesions seen on magnetic resonance imaging in the pivotal trials of these agents. This situation has changed in the last year, with the outcomes of three randomised clinical trials comparing the efficacy and safety of glatiramer acetate with that of a high-dose interferon-beta in relapsing remitting multiple sclerosis. These are the REGARD, BEYOND and BECOME trials. In the REGARD trial, 764 patients were randomised to treatment with either interferon-beta 1a sc 44 microg or glatiramer acetate for 96 weeks; no significant difference in the time to first relapse was observed. The largest of the three comparative studies, the BEYOND trial, compared treatment with interferon-beta 1b sc 500 microg, interferon-beta 1b sc 250 microg or glatiramer acetate for two years in 2,244 patients. The hazard ratio for multiple relapses was close to unity for comparisons between all groups, indicating equivalent efficacy in all three treatment arms. Relapse rates (around 0.3 relapses/year) in all these studies were much lower than anticipated and lower than those reported a decade previously in the pivotal trials of beta-interferons and glatiramer acetate. No unexpected safety issues were identified in any of these studies. The completion of these direct comparative studies has considerably enriched the clinical evidence database by contributing large numbers of patients. This provides an invaluable contribution for helping the physician make an informed choice about treatment. The results of the direct comparative studies provide evidence that glatiramer acetate and high-dose interferon-beta preparations have comparable clinical efficacy.

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    ABSTRACT: Multiple sclerosis (MS) is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNbeta)-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNbeta-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNbeta-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNbeta-1b was administered to still-active secondary progressive MS. IFNbeta-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNbeta-1b still remains a first-line therapy with a fundamental role in all stages of the disease.
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