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.

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.

• Authors: 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
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 79 Issue 5 Pg. 595-604 (05 2020) ISSN: 1468-2060 [Electronic] England
• PMID: 32253184 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 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.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• IL17A protein, human
• IL17F protein, human
• Interleukin-17
• bimekizumab

Topics

• Adult
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Biomarkers (metabolism)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Europe
• Female
• Follow-Up Studies
• Humans
• Interleukin-17 (metabolism)
• Internationality
• Male
• Maximum Tolerated Dose
• Middle Aged
• Reference Values
• Risk Assessment
• Severity of Illness Index
• Spondylitis, Ankylosing (diagnosis, drug therapy)
• Treatment Outcome
• United States