Dual Neutralization of IL-17A and IL-17F with Bimekizumab in Patients with Active Ankylosing Spondylitis: 48-Week Efficacy and Safety Results from a Phase 2b, Randomized, Blinded, Placebo-Controlled, Dose-Ranging Study
Désirée van der Heijde, MD, PhD
Leiden University Medical Center, Leiden, Netherlands
The monoclonal antibody bimekizumab potently and selectively neutralizes both IL-17A and IL-17F and showed promising results in early clinical trials as a novel therapeutic approach to ankylosing spondylitis (AS).  In a 12-week study, dual neutralization of IL-17A and IL-17F with bimekizumab provided rapid and substantial clinical improvements in patients with psoriasis, with no unexpected or dose-related safety findings. Herein, the 48-week efficacy and safety of bimekizumab in patients with active AS are reported.
Eligible patients with active AS (Bath AS Disease Activity Index (BASDAI) ≥4; spinal pain ≥4 (0–10)) who fulfilled the modified New York criteria with inadequate response/intolerance to NSAIDs were randomized 1:1:1:1:1 to sc bimekizumab 16 mg, 64 mg, 160 mg, 320 mg, or placebo every 4 weeks, for 12 weeks (double-blind period).
Subsequently, patients in the 16 mg, 64 mg, and placebo groups were re-randomized 1:1 to sc bimekizumab 160 mg or 320 mg every 4 weeks through week 48; dosing in the original 160 mg and 320 mg groups was unchanged through week 48 (dose-blind period).
Efficacy endpoints included ASAS20, ASAS40, ASAS5/6, ASAS partial remission, and AS Disease Activity Score with C-reactive Protein (ASDAS-CRP); data presented for all pts who began the dose-blind period and received ≥1 dose of study drug.
Non-responder imputation accounted for missing binary scores; multiple imputation accounted for missing continuous values.
The primary endpoint was ASAS40 response rate at week 12.
Following positive results at week 12, bimekizumab showed sustained improvements in patients with active AS across multiple measures of disease activity up to week 48.
Bimekizumab was generally well tolerated and no new or unexpected safety findings were identified.
Key messages/Clinical perspectives
These data provide evidence that neutralizing both IL-17F and IL17A with bimekizumab may be a promising therapeutic option for patients with AS, warranting further investigation across the entire spectrum of spondyloarthropathies.
Van der Heijde D, Gensler LS, Deodhar A, et al. EULAR 2018 - LB0001. Dual neutralisation of il-17A and il-17F with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study. Ann Rheum Dis 2018;77(Suppl. 2):A70
Presenter disclosure: The presenter has reported relationships with AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo Smith and Klein, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB.