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.
RCT Entities:
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.
Authors: Damiano Paolicelli; A Manni; A Iaffaldano; V Di Lecce; M D'Onghia; P Iaffaldano; M Trojano Journal: Eur J Clin Pharmacol Date: 2016-06-01 Impact factor: 2.953
Authors: Meenu Wadhwa; Meena Subramanyam; Susan Goelz; Jaya Goyal; Vijay Jethwa; Wendy Jones; James G Files; Daniel Kramer; Chris Bird; Paula Dilger; Michael Tovey; Christophe Lallemand; Robin Thorpe Journal: J Interferon Cytokine Res Date: 2013-07-13 Impact factor: 2.607
Authors: Hans-Peter Hartung; Bernd Kieseier; Douglas S Goodin; Barry Gw Arnason; Giancarlo Comi; Stuart Cook; Massimo Filippi; Douglas R Jeffery; Ludwig Kappos; Timon Bogumil; Brigitte Stemper; Rupert Sandbrink; Yukiko Nakada; Haruhiko Nakajima; Susanne Schwenke; Stephan Lehr; Jürgen Heubach; Christoph Pohl; Joachim Reischl Journal: J Neuroinflammation Date: 2012-06-15 Impact factor: 8.322