Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials

Abstract

Objectives: Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum.

Methods: In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24.

Results: 254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low.

Conclusions: Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

Keywords: Autoimmune Diseases; Biological Therapy; Cytokines; Inflammation; Spondylitis, Ankylosing.

Figure 1

Key efficacy outcomes over time. Randomised set. ^aPrimary endpoint; ^bRanked secondary endpoint. Error bars show SE. All statistical tests were performed at a two-sided alpha level of 0.05. For binary endpoints, p values were calculated by logistic regression with treatment, MRI/CRP classification and region (BE MOBILE 1) or treatment, prior TNFi exposure and region (BE MOBILE 2) as factors. For continuous endpoints, p values were obtained by ANCOVA with treatment, MRI/CRP classification and region (BE MOBILE 1) or treatment, prior TNFi exposure and region (BE MOBILE 2) as fixed effects, and baseline values as covariates. ***p<0.001. ANCOVA, analysis of covariance; ASAS40, Assessment of Spondyloarthritis international Society 40% response; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BKZ, bimekizumab; CfB, change from baseline; CRP, C-reactive protein; MI, multiple imputation; nr-axSpA, non-radiographic axial spondyloarthritis; NRI, non-responder imputation; PBO, placebo; Q4W, every 4 weeks; r-axSpA, radiographic axial spondyloarthritis; TNFi, tumour necrosis factor inhibitor.

Figure 2

ASDAS disease states over time. Randomised set. Exploratory endpoint. Data reported are MI. VHD: ASDAS >3.5; HD: ASDAS ≥2.1 to ≤3.5; LD: ASDAS ≥1.3 to <2.1; ID: ASDAS <1.3. ASDAS, Ankylosing Spondylitis Disease Activity Score; BKZ, bimekizumab; HD, high disease; ID, inactive disease; LD, low disease; MI, multiple imputation; nr-axSpA, non-radiographic axial spondyloarthritis; PBO, placebo; Q4W, every 4 weeks; r-axSpA, radiographic axial spondyloarthritis; VHD, very high disease.

Figure 3

Objective signs of inflammation. Randomised set. Exploratory endpoints. Error bars show SD. (A) n=128 (BKZ) and n=126 (PBO) in BE MOBILE 1, n=221 (BKZ) and n=111 (PBO) in BE MOBILE 2; (B) At BL, n=79 (BKZ) and n=68 (PBO) in BE MOBILE 1, n=83 (BKZ) and n=45 (PBO) in BE MOBILE 2. At week 16, n=77 (BKZ), n=60 (PBO) in BE MOBILE 1, n=79 (BKZ) and n=43 (PBO) in BE MOBILE 2; (C) At BL, n=75 (BKZ) and n=65 (PBO) in BE MOBILE 1, n=82 (BKZ) and n=45 (PBO) in BE MOBILE 2. At week 16, n=73 (BKZ) and n=58 (PBO) in BE MOBILE 1, n=79 (BKZ) and n=43 (PBO) in BE MOBILE 2. MRI Berlin spine score ranges from 0 to 69; lower scores indicate less spinal inflammation and negative changes represent improvements. MRI SPARCC SIJ inflammation scores range from 0 to 72; lower scores indicate less SIJ inflammation and negative changes represent improvements. BKZ, bimekizumab; BL, baseline; CfB, change from baseline; hs-CRP, high-sensitivity C-reactive protein; MI, multiple imputation; nr-axSpA, non-radiographic axial spondyloarthritis; OC, observed case; PBO, placebo; Q4W, every 4 weeks; r-axSpA, radiographic axial spondyloarthritis; SIJ, sacroiliac joint; SPARCC, Spondyloarthritis Research Consortium of Canada.