Neutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial

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Neutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial

TitleNeutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial
Publication TypeJournal Article
Year of Publication2012
AuthorsGoodin, DS, Hartung, HP, O'Connor, P, Filippi, M, Arnason, B, Comi, G, Cook, S, Jeffery, D, Kappos, L, Bogumil, T, Knappertz, V, Sandbrink, R, Beckmann, K, White, R, Petkau, J, Pohl, C
JournalMultiple Sclerosis Journal
Volume18
Pagination181-195
Date PublishedFEB
Type of ArticleArticle
ISSN1352-4585
KeywordsBEYOND study, Interferon beta-1b, multiple sclerosis, neutralizing antibodies
Abstract

Background: The frequency and impact of neutralizing antibodies (NAbs) to interferon beta-1b (IFN beta-1b) on clinical and radiographic outcomes is controversial. Objective: To assess NAb impact in the BEYOND study. Methods: 2244 patients were randomized (2:2:1) to receive IFN beta-1b, either 250 or 500 mu g, or glatiramer acetate, 20 mg, and observed for 2-3.5 years. NAb titers were determined every 6 months. A titer >= 20 NU/ml was considered NAb positive. Efficacy was compared between NAb-positive and NAb-negative patients, using comprehensive statistical analyses, taking into account the delayed appearance of NAbs, the time-dependent changes in the relapse rate, spontaneous reversions to NAb-negative status, NAb-titer level, and also adjusting for baseline factors. Results: In the IFN beta-1b 250 mu g group, NAb-positive titers were detected (>= once) in 319 patients (37.0%); of these, 112 (35.1%) reverted to NAb-negative status. In the IFN beta-1b 500 mu g group, 340 patients (40.7%) became NAb-positive and 119 (35.0%) reverted to NAb-negative status. In both IFN beta groups, especially the 250 mu g arm, NAb-positive status was not associated with a convincing impact on any clinical outcome measure by any statistical analysis. By contrast, in both IFN beta groups, NAbs were associated with a very consistent deleterious impact on most MRI outcomes. Conclusion: There was a notable dissociation between the impact of NAbs on MRI and clinical outcomes. On MRI measures, the impact was consistent and convincing, whereas on clinical measures a negative impact of NAbs was not found. The basis for this clinico-radiographic paradox is unknown but it suggests that the relationship between NAbs and the therapeutic effects of IFN beta-1b is complex.

DOI10.1177/1352458511418629