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

• Published in: Journal of neurology 2016-07, Vol.263 (7), p.1287-1295
• Main Authors: Havrdová, Eva, Belova, Anna, Goloborodko, Alla, Tisserant, Anne, Wright, Andrew, Wallstroem, Erik, Garren, Hideki, Maguire, Ralph Paul, Johns, Donald R.
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adolescent; Adult; Antibodies, Monoclonal - adverse effects; Arthritis; Brain - diagnostic imaging; Brain - drug effects; Cytokines; Disability Evaluation; Double-Blind Method; Female; Follow-Up Studies; Hepatitis; Humans; Immunologic Factors - adverse effects; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Neurology; Neuroradiology; Neurosciences; Original Communication; Retrospective Studies; Treatment Outcome; Young Adult
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-016-8128-x

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.