Abstract
The objective of this study was to assess the effect of secukinumab, a monoclonal antibody that inhibits interleukin (IL)-17A, on number of new active brain magnetic resonance imaging (MRI) lesions in subjects with relapsing-remitting multiple sclerosis (MS). Subjects (N = 73) were randomized 1:1 to secukinumab 10 mg/kg or placebo by intravenous infusion at weeks 0, 2, 4, 8, 12, 16, and 20. MRI scans were obtained within 30 days prior to randomization, on a monthly basis during the treatment period, and at study completion. The primary endpoint was the cumulative number of combined unique active lesions (CUAL) observed on brain MRI scans from week 4 to week 24. Compared with placebo, secukinumab non-significantly reduced the number of CUAL observed on 4-weekly MRI from week 4 to 24 (primary endpoint) by 49 % (95 % CI −10 to 77 %; P = 0.087) and significantly reduced the number of cumulative new gadolinium-enhancing T1 lesions by 67 % (31–84 %, P = 0.003). CUAL reductions were progressively greater from week 4 (1 %) to week 16 (49 %) and persisted until end-study (50 %). There were no serious adverse events; the adverse event rate was comparable to placebo (53 versus 49 %), although mild-to-moderate infection was somewhat more frequent (37 versus 23 %). This proof-of-concept study provides the first evidence that blocking IL-17A with an antibody may reduce MRI lesion activity in MS. Further studies are needed to confirm this finding and determine the magnitude of effect.
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Acknowledgments
This study was supported by the Novartis Institutes for BioMedical Research. The authors thank the subjects and investigators who participated in this study. Barry Weichman, Ph.D., and Eric Justice of BioScience Communications, New York, NY, provided writing and editorial assistance, respectively, supported by Novartis Pharma AG. E. H. has been supported by the Czech Ministry of Education (PRVOUK-P26/LF1/4).
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E. H. has received speakers’ honoraria and research grant support from Bayer Schering Healthcare, Biogen Idec, Sanofi Genzyme, Merck Serono, Novartis, and Teva, and has received compensation for Advisory Board activities from Biogen Idec, Sanofi Genzyme, Merck Serono, Novartis, and Teva. A. B. and A. G. have no competing financial interests to disclose. A. T., A. W., E. W., and R. P. M. are employees of, and own stock/stock options in Novartis. H. G. was an employee of Novartis at the time the study was conducted. D. R. J. was an employee of Novartis and owned stock/stock options in Novartis at the time the study was conducted.
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The study was conducted according to the ethical principles of the Declaration of Helsinki, and the protocol was approved by the Independent Ethics Committee at each site. The study is registered with ClinicalTrials.gov (NCT01051817) and the full protocol is available from the sponsor. The results of this study were presented, in part, at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Lyon, France, October 10–13, 2012.
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All subjects provided informed consent prior to randomization.
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On behalf of the AIN457 for MS Study Group.
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Havrdová, E., Belova, A., Goloborodko, A. et al. Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study. J Neurol 263, 1287–1295 (2016). https://doi.org/10.1007/s00415-016-8128-x
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DOI: https://doi.org/10.1007/s00415-016-8128-x