Clinical relevance of anti-drug antibodies with interferon beta-1b therapy in multiple sclerosis

Abstract

Interferon beta-1b (IFNβ-1b; Betaferon®/Betaseron®) is an effective treatment for relapsing forms of multiple sclerosis (MS). It was the first immunomodulatory therapy to receive approval for this indication in 1993 in the USA and in 1995 in Europe. It remains the only high-dose, high-frequency treatment with proven efficacy in patients with a clinical demyelinating event, RRMS and SPMS. Several large controlled studies have been performed, including 16 years follow-up of patients, providing a unique data set to evaluate long-term safety and efficacy. Results obtained from several studies have shown an inconsistent impact of neutralizing antibodies (NAb) to IFNβ-1b, unlike NAb to other IFNβ therapies. Although patient heterogeneity and the use of different NAb assays are involved, this reflects intrinsic differences between the respective IFNβ-1b versus IFNβ-1a molecules as well as their sensitivity to NAb effects. When evaluating the occurrence and the impact of NAb during different IFNβ therapies, standardization is a necessity. Three phase III trials of IFNβ-1b, in which the same assay methodology was applied, suggest that NAb to IFNβ-1b are transient, mostly of low to moderate titre and have no effect on disability progression with only limited effect on relapse rate. Two controlled studies showed better efficacy of high dose, high frequency beta-interferon treatment even in NAb-positive patients over low dose, low frequency beta-interferon treatment in NAb-negative individuals. Given the overall clinical efficacy of IFNβ-1b, the inconsistent data regarding the effect of NAb to IFNβ-1b on treatment outcome, and the unpredictable course of disease in a given patient, treatment decisions should be based on patient response to therapy, not on NAb status. This position is endorsed by current regulatory and neurology association guidelines and is reflected in the package insert information. Multiple Sclerosis 2007; 13: S21—S27 http://msj.sagepub.com

Keywords

Antibodies Betaseron®Betaferon®Interferon beta-1b multiple sclerosis neutralizing antibodies

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