Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study

J Neurol. 2016 Jul;263(7):1287-95. doi: 10.1007/s00415-016-8128-x. Epub 2016 May 3.

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.

Keywords: Clinical trial; MRI; Multiple sclerosis; Secukinumab.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Disability Evaluation
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / adverse effects*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • secukinumab