title: Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study.
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.
authors.affiliation: Department of Neurology, Center of Clinical Neuroscience, First Faculty of Medicine and General Teaching Hospital, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdová
authors.affiliation: Institute for Traumatology and Orthopaedics of Minzdrav, Nizhny Novgorod, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Belova
authors.affiliation: Department of Neurosurgery, Odessa Regional Clinical Hospital, Odessa, Ukraine.
authors.forename: Alla
authors.initials: A
authors.lastname: Goloborodko
authors.affiliation: Neuroscience Translational Medicine, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 12, 4002, Basel, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Tisserant
authors.affiliation: Neuroscience Translational Medicine, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 12, 4002, Basel, Switzerland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wright
authors.affiliation: Neuroscience Translational Medicine, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 12, 4002, Basel, Switzerland. erik.wallstroem@novartis.com.
authors.forename: Erik
authors.initials: E
authors.lastname: Wallstroem
authors.affiliation: Neuroscience Translational Medicine, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 12, 4002, Basel, Switzerland.
authors.forename: Hideki
authors.initials: H
authors.lastname: Garren
authors.affiliation: Neuroscience Translational Medicine, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 12, 4002, Basel, Switzerland.
authors.forename: Ralph Paul
authors.initials: RP
authors.lastname: Maguire
authors.affiliation: Neuroscience Translational Medicine, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 12, 4002, Basel, Switzerland.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Johns
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; C555450:secukinumab
keywords: Clinical trial; MRI; Multiple sclerosis; Secukinumab