Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial

Abstract

ObjectiveTo investigate the efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).MethodsIn a multicentre, placebo-controlled phase 3 study (NCT02985983) conducted at 48 sites across Japan, Korea and Taiwan, patients with axSpA were randomised 1:1 to receive subcutaneous brodalumab 210 mg (n=80) or placebo (n=79) at baseline, weeks 1 and 2 and every 2 weeks thereafter, during the 16-week double-blind period. The primary endpoint was the proportion of patients with Assessment of SpondyloArthritis International Society (ASAS) 40 response at week 16. Secondary endpoints included the proportion of patients with ASAS 20 response and change in Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) at week 16 and safety.ResultsASAS 40 response rate (n/N; 95% CI) was 43.8% (35/80; 32.7, 55.3) with brodalumab vs 24.1% (19/79; 15.1, 35.0) with placebo (rate difference, 19.7% (5.3, 34.1); p=0.018 by stratified Cochran-Mantel-Haenszel test). ASAS 20 response rate (n/N; 95% CI) was 67.5% (54/80; 56.1, 77.6) vs 41.8% (33/79; 30.8, 53.4) and least squares mean change (95% CI) from baseline (brodalumab, 2.660; placebo, 2.716) in ASDAS-CRP was –1.127 (–1.322, –0.931) with brodalumab vs –0.672 (–0.872, –0.473) with placebo at week 16. Treatment-emergent adverse events were reported in 44 (55%) and 45 (57%) patients in the brodalumab and placebo groups, respectively.ConclusionBrodalumab demonstrated a significant improvement at week 16 in patients with active axSpA. Safety of brodalumab was consistent with that reported in previous global/Japanese psoriasis studies.

Secukinumab in axial spondyloarthritis: a narrative review of clinical evidence

“… 24 Further anti-IL-17 biologics, such as brodalumab and bimekizumab, are being evaluated in clinical trials in patients with axSpA; these therapies, however, are still in clinical development and are not currently indicated in this patient population. 25 , 26 …”

2022 French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis

“…Secukinumab was shown to be effective on axial manifestations of PsA (Maximise study) [85]. Other IL17 inhibitors are being evaluated: bimekizumab (dual IL-17A/17F inhibitor) [86] and brodalumab (IL-17 A receptor antagonist) [87].…”

New developments in ankylosing spondylitis—status in 2021

“…Netakimab, a humanized IgG1 mAb targeting IL-17A, was found superior to placebo in TNFi-naïve axSpA patients [ 54 ]. A phase III study of brodalumab, a mAb inhibiting the IL-17 receptor A, in Asian patients with AS and nr-axSpA met its primary end point [ 55 ]. Bimekizumab, an IgG1 monoclonal antibody that binds to an epitope expressed on both IL-17A and IL-17F, selectively neutralizes both cytokines [ 56 ].…”