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

Douglas S. Goodin, Hans Peter Hartung, Paul O'Connor, Massimo Filippi, Barry Arnason, Giancarlo Comi, Stuart Cook, Douglas Jeffery, Ludwig Kappos, Timon Bogumil, Volker Knappertz, Rupert Sandbrink, Karola Beckmann, Rick White, John Petkau, Christoph Pohl

Research output: Contribution to journalArticlepeer-review


Background: The frequency and impact of neutralizing antibodies (NAbs) to interferon beta-1b (IFNβ-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 IFNβ-1b, either 250 or 500 μg, 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 IFNβ-1b 250 μg group, NAb-positive titers were detected (≥ once) in 319 patients (37.0%); of these, 112 (35.1%) reverted to NAb-negative status. In the IFNβ-1b 500 μg group, 340 patients (40.7%) became NAb-positive and 119 (35.0%) reverted to NAb-negative status. In both IFNβ groups, especially the 250 μg arm, NAb-positive status was not associated with a convincing impact on any clinical outcome measure by any statistical analysis. By contrast, in both IFNβ 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 IFNβ-1b is complex.

Original languageEnglish
Pages (from-to)181-195
Number of pages15
JournalMultiple Sclerosis Journal
Issue number2
Publication statusPublished - 2012


  • BEYOND study
  • interferon beta-1b
  • multiple sclerosis
  • neutralizing antibodies

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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