Journal Article

Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study

Baraliakos, Xenofon, Baeten, Dominique, Dougados, Maxime, Poddubnyy, Denis, Goldammer, Nadine, Coarse, Jason, Farmer, Mary Katherine, Deodhar, Atul, Oortgiesen, Marga, Gensler, Lianne S, van der Heijde, Désirée, Kivitz, Alan

2020

Overview

ObjectivesBimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS).MethodsAdults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data).Results303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%–46.7% vs 13.3%; p<0.05 all comparisons; OR vs placebo 2.6–5.5 (95% CI 1.0 to 12.9)). A significant dose-response was observed (p<0.001). The primary end point was supported by all secondary efficacy outcomes. At week 48, 58.6% and 62.3% of patients receiving bimekizumab 160 and 320 mg throughout the study achieved ASAS40, respectively (NRI); similar ASAS40 response rates were observed in re-randomised patients. During the double-blind period, treatment-emergent adverse events occurred in 26/60 (43.3%) patients receiving placebo and 92/243 (37.9%) receiving bimekizumab.ConclusionsBimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies.Trial registration number NCT02963506.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Adult / Ankylosing spondylitis / Antibodies, Monoclonal, Humanized - administration & dosage / Arthritis / Biomarkers - metabolism / Chronic illnesses / Cytokines / Disease control / DMARDs (biologic) / Dose-Response Relationship, Drug / Double-Blind Method / Double-blind studies / Drug Administration Schedule / Drug dosages / Europe / Female / Follow-Up Studies / Humans / Infections / Inflammation / Inflammatory bowel disease / Inflammatory diseases / Interleukin-17 - metabolism / Internationality / Male / Maximum Tolerated Dose / Middle Aged / Monoclonal antibodies / Patients / Psoriasis / Quality of life / Reference Values / Rheumatic diseases / Risk Assessment / Severity of Illness Index / Spondylitis, Ankylosing - diagnosis / Spondylitis, Ankylosing - drug therapy / Spondyloarthritis / Suicides & suicide attempts / TNF inhibitors / treatment / Treatment Outcome / Tumor necrosis factor-TNF / United States