Background/Purpose: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. Previous analyses of phase (Ph)2b/3 safety data (data cut-off: July 2023) demonstrated that BKZ was generally well tolerated by patients (pts) with axial spondyloarthritis (axSpA; exposure: 2,513.8 patient-years [PY]) and psoriatic arthritis (PsA; exposure: 3,655.9 PY) longer-term over ~2 years.1 Here, we present updated safety analyses from these studies, including another year of BKZ exposure from the ongoing Ph3 open-label extensions (OLEs).

Methods: Safety data are reported for two pools, each comprising one Ph2b and two Ph3 studies and their OLEs, in pts with axSpA (non-radiographic and radiographic) and PsA, respectively (Figure).1 Exposure-adjusted incidence rates (EAIR)/100 PY and n (%) are reported for treatment‑emergent adverse events (TEAEs; classified using MedDRA v19.0) among pts who received ≥1 dose of subcutaneous BKZ 160 mg every four weeks (wks; Q4W) in any treatment period. Data are reported to the data-cuts of September 2024 (axSpA) or August 2024 (PsA) in the ongoing BE MOVING and BE VITAL OLEs (corresponding with ≥156 wks of total Ph3 study participation; Figure).

Results: The axSpA safety pool included 848 pts (2,748.9 PY); the PsA safety pool included 1,409 pts (4,264.7 PY; Figure). Comparison of safety data with previous analyses did not indicate an increase in EAIRs of the majority of TEAEs; some TEAEs demonstrated an EAIR decrease with longer BKZ exposure, including Candida infections.1 The 3 most frequently reported TEAEs in pts with axSpA and PsA (by preferred term) were corona virus infection, nasopharyngitis, and upper respiratory tract infection (Table). Safety topics of interest are reported in the Table. Serious infections occurred at an EAIR/100 PY of 1.4 in pts with axSpA and 1.2 in PsA. The EAIR/100 PY of fungal infections was 8.1 in axSpA and 7.1 in PsA. Most fungal infections were mucocutaneous and mild/moderate in severity; oral candidiasis was the most common fungal infection. Permanent BKZ discontinuation due to oral candidiasis was infrequent (axSpA: 0.2/100 PY; PsA: 0.3/100 PY). No systemic fungal infections were reported. No cases of active tuberculosis, histoplasmosis, coccidioidomycosis or blastomycosis were reported in any study. The EAIR/100 PY of hepatic events was 4.9 in axSpA and 4.6 in PsA; most were transient liver enzyme abnormalities (Table; no confirmed cases of Hy’s law). For adjudicated definite/probable IBD, the EAIR/100 PY was 0.7 in axSpA and 0.2 in PsA. The uveitis EAIR/100 PY was 1.2 in axSpA and 0.1 in PsA. Rates of suicidal ideation/behavior were low, and no cases of completed suicide were reported (Table). Rates of other safety topics of interest (major adverse cardiovascular events, malignancies, neutropenia, administration/injection site reactions) are shown in the Table.No additional deaths occurred since the previous data-cut (Table).

Conclusion: With an additional year of exposure, the long-term safety profile of BKZ in pts with axSpA and PsA remained consistent with prior analyses; no new safety signals or concerns were raised.1References: 1. Mease PJ. Arthritis Rheumatol 2024;76(suppl 9). Abstract 2367.

Figure. The two safety pools (axSpA, PsA) of patients treated with BKZ 160 mg Q4W across six phase 2b/3 studies and their open-label extensions

Table. Summary of TEAEs reported up to the phase 3 data cut (axSpA: September 2024; PsA: August 2024)

ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-safety-and-tolerability-of-bimekizumab-treatment-across-phase-2b-and-phase-3-studies-in-patients-with-axial-spondyloarthritis-or-psoriatic-arthritis-3-year-update-from-the-phase-3-studies/