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

Objective: To investigate the efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).

Methods: In 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.

Results: ASAS 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.

Conclusion: Brodalumab 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.

Keywords: ankylosing; biological therapy; inflammation; spondylitis; therapeutics.

Figure 1

Patient disposition. *Did not meet the study criteria for AS or nr-axSpA, as judged by the central image readers. ^†Failed to meet the inclusion criteria or met one of the exclusion criteria. AS, ankylosing spondylitis; axSpA, axial spondyloarthritis; nr-axSpA, non-radiographic axSpA.

Figure 2

Response rates (full analysis set). (A) ASAS 40 response rate in patients with axSpA. (B) ASAS 20 response rate in patients with axSpA. (C) ASAS 40 response rate in patients with AS vs nr-axSpA. (D) ASAS 40 response rate in patients with HLA-B27 positive vs HLA-B27 negative. (E) ASAS 40 response rate in patients with CRP abnormal vs CRP normal. *Data are presented in online supplemental table S5. AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis International Society; axSpA, axial spondyloarthritis; CRP, C-reactive protein; HLA, human leucocyte antigen; nr-axSpA, non-radiographic axSpA; ULN, upper limit of normal.

Figure 3

ASDAS-CRP (full analysis set). (A) Change in ASDAS-CRP score from baseline at each efficacy timepoint over 16 weeks. *Baseline-observation-carried-forward ASAS response at week 16. (B) ASDAS-CRP response rate by disease improvement. Disease improvement was defined as clinically important and major for change from baseline in the ASDAS-CRP score of ≥1.1 and ≥2.0, respectively. (C) ASDAS-CRP response rate by disease activity state in the brodalumab (left) and placebo (right) groups. Disease activity state was defined by ASDAS-CRP score as follows: score <1.3, inactive disease; 1.3 to <2.1, low disease activity; 2.1 to <3.5, high disease activity; and ≥3.5, very high disease activity. ASAS, Assessment of SpondyloArthritis International Society; ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score using C-reactive protein; LS, least squares.