Long-term safety and sustained efficacy of bimekizumab in patients with ankylosing spondylitis (radiographic axial spondyloarthritis): 5-year results from BE AGILE (phase 2b) and its open-label extension

Abstract

Objective: Assess long-term safety, tolerability and efficacy of bimekizumab in ankylosing spondylitis (radiographic axial spondyloarthritis (r-axSpA)).

Methods: Patients with active r-axSpA completing the dose-ranging 48-week randomised controlled trial could enrol in the open-label extension, where patients received bimekizumab 160 mg every 4 weeks. Safety (exposure-adjusted incidence rates/100 patient-years (EAIRs)) and efficacy outcomes (binary: non-responder imputation (NRI) and observed case (OC); continuous: multiple imputation (MI)) are presented through 256 weeks.

Results: From Weeks 0-256, 289/303 (95.4%) patients had ≥1 treatment-emergent adverse event (TEAE); most frequent were nasopharyngitis (21.8%) and upper respiratory tract infection (14.5%). The EAIR of fungal infections was 7.4 (Candida infections: 2.6; oral candidiasis: 2.2); none systemic. EAIR of serious infections was 1.4; no active tuberculosis was reported. Active inflammatory bowel disease and anterior uveitis EAIRs were 0.8 and 0.7, respectively. 202/303 (66.7%) patients completed Week 256. 42 (13.9%) patients discontinued treatment due to TEAEs.Efficacy at Week 48 was maintained for 5 years. At Week 256, NRI analysis showed 49.7% (OC: 73.1%) and 41.6% (OC: 71.1%) of patients achieved Assessment of SpondyloArthritis International Society 40% (ASAS40) response and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity, respectively. Mean (SE; MI) ASDAS improved from 3.9 (0.1) at baseline to 2.1 (0.1) at Week 48, which was maintained to Week 256. Improvements in pain, fatigue, physical function and health-related quality of life were sustained.

Conclusions: The safety profile of bimekizumab after 5 years of treatment remained consistent with previous reports, with no new safety signals identified. 5-year efficacy was sustained in this r-axSpA population following robust disease control achieved at Week 48.

Trial registration numbers: NCT02963506; NCT03355573.

Keywords: Axial Spondyloarthritis; DMARD; Spondylitis, Ankylosing; Treatment.

Figure 1. Safety overview by study year. TEAEs are reported for the BE AGILE safety set (patients who received ≥1 dose of bimekizumab within the study period) and who were at risk at the start of the specified study period shown. TEAEs are defined according to Medical Dictionary for Regulatory Activities V.19.0. Year 1: >0 to 52 weeks (n=303; 289.1 PY), Year 2: >52 to 104 weeks (n=269; 245.9 PY), Year 3: >104 to 156 weeks (n=236; 228.8 PY), Year 4: >156 to 208 weeks (n=223; 217.7 PY), Year 5: >208 to 260 weeks (n=216; 208.8 PY). EAIR, exposure-adjusted incidence rate; PY, patient-years; TEAE, treatment-emergent adverse event.

Figure 2. ASAS40, ASDAS LDA, ASDAS-ID and ASDAS-CII responses to Week 256 (NRI, MI, OC). BE AGILE FAS (all randomised patients who received ≥1 dose of BKZ and had a valid measurement of the ASAS components at baseline; N=303) for Weeks 0–12; unless otherwise stated, DBS (patients who started the dose-blind period at Week 12 and received ≥1 dose of BKZ during the dose-blind period, including the dose at Week 12; N=296) for Weeks 12–256. Data for OLE FAS are also reported (patients who entered the OLE and had ≥1 scheduled efficacy assessment at OLE entry; N=249 (248 patients included in the MI model)) for Weeks 48–256. Data reported as NRI, MI and OC as indicated. In the NRI analyses, patients who did not enter the OLE were considered non­-responders from Week 48 onwards. ASAS40, Assessment of SpondyloArthritis international Society 40% response; ASDAS, Ankylosing Spondylitis Disease Activity Score; ASDAS-CII, ASDAS clinically important improvement; ASDAS-ID, ASDAS inactive disease; ASDAS LDA, ASDAS low disease activity; BKZ, bimekizumab; DBS, double-blind set; FAS, full analysis set; MI, multiple imputation; NRI, non-responder imputation; OC, observed case; OLE, open-label extension; Q4W, every 4 weeks.

Figure 3. ASDAS, BASDAI, BASFI and total spinal pain absolute values and change from baseline to Week 256 (MI). BE AGILE FAS (all randomised patients who received ≥1 dose of BKZ and had a valid measurement of the ASAS components at baseline; N=303) for Weeks 0–12; unless otherwise stated, DBS (patients who started the dose-blind period at Week 12 and received ≥1 dose of BKZ during the dose-blind period, including the dose at Week 12; N=296) for Weeks 12–256. Data for OLE FAS are also reported (patients who entered the OLE and had ≥1 scheduled efficacy assessment at OLE entry; N=249) for Weeks 48–256. Baseline ASDAS, BASDAI, BASFI and total spinal pain are shown for the DBS. Data reported as MI. ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BKZ, bimekizumab; CfB, change from baseline; DBS, dose-blind set; FAS, full analysis set; MI, multiple imputation; OLE, open-label extension; Q4W, every 4 weeks.