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

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

Abstract

Objectives: Bimekizumab 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).

Methods: Adults 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).

Results: 303 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.

Conclusions: Bimekizumab 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.

Keywords: DMARDs (biologic); ankylosing spondylitis; spondyloarthritis; treatment.

Conflict of interest statement

Competing interests: DvdH reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB Pharma, and is Director of Imaging Rheumatology BV. LSG reports grants and personal fees from AbbVie, Amgen, Novartis, Pfizer and UCB Pharma, and personal fees from Galapagos, Janssen and Eli Lilly. AD reports personal fees from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos and Janssen, and grants and personal fees from AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and UCB. DP reports personal fees from UCB Pharma, BMS, Roche and Celgene, and grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis and Pfizer. XB reports personal fees from AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, MSD, Novartis, Pfizer and UCB Pharma, and grant/research support from Abbvie, MSD and Novartis. AK reports research support from Altoona Centernical Research, PC, during the conduct of the study; Advisory Committee or Review Panel for AbbVie, Janssen, UCB Pharma and Boehringer Ingelheim; speaking and teaching for Celgene, Horizon, Merck and Novartis; Advisory Committee or Review Panel, speaking and training for Genzyme; Advisory Committee or Review Panel, speaking/training; consultant, and stocks for Pfizer and Sanofi; Advisory Committee or Review Panel, speaking/training and consultant for Regeneron; consultant for SUN Pharma Advanced Research; Speaker and Steering Committee for Flexion; Stocks from Amgen, Gilead and GSK and Speaker for AbbVie. MO, DB and NG are employees of UCB Pharma and own stocks and stock options. JC is an employee of UCB Pharma. MKF was an employee of UCB Pharma at the time the study was conducted (current employee of Kezar Life Sciences). MD reports grants and personal fees from UCB, Eli Lilly, Novartis, Pfizer, AbbVie and Merck.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
(A) ASAS40 response at week 12 (primary efficacy end point; FAS, NRI). *P value vs placebo calculated from a logistic regression model including fixed effects for treatment, geographic region and prior TNF inhibitor exposure; *p

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