Bimekizumab Safety in Patients with Psoriasis Achieving Complete Skin Clearance: 4-year Analysis from 5 Phase 3/3b Trials

Abstract

Introduction Bimekizumab (BKZ) is an IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A,¹ which has demonstrated a favorable safety profile and was well-tolerated through 5 years in patients with moderate to severe plaque psoriasis.^2,3 In phase 3 trials, 59–68% of patients treated with BKZ achieved 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100) at Week 16,^4–7 and 65–72% did so at Year 1 (Week 48/52/56).^4–6 It may be suggested that patients with greater skin clearance have greater inhibition of the IL-17 pathway, which could potentially make them more likely to experience certain adverse events. Here, safety of BKZ is reported through 4 years of treatment in patients with PASI 100 at the end of the initial treatment (Week 16) and double-blinded periods (Week 48; last common timepoint in the double-blinded periods of the included studies).

Procedure Data were pooled from the BE SURE (NCT03412747), BE VIVID (NCT03370133), and BE READY (NCT03410992) phase 3 trials, their open-label extension (OLE) BE BRIGHT (NCT03598790) and the BE RADIANT (NCT03536884) phase 3b trial (including its OLE).^4–8 Included patients were randomized to BKZ 320 mg every 4 weeks (Q4W) and received BKZ Q4W or Q8W thereafter (patients who switched to placebo at Week 16 of BE READY were excluded). Treatment-emergent adverse events (TEAEs) are reported for up to 4 years using exposure-adjusted incidence rates (EAIRs) per 100 patient‑years (PY) for patients who achieved PASI 100 at Week 16 and patients who achieved PASI 100 at Week 48. Safety data (up to 4 years) are also presented for all patients randomized to BKZ in phase 3/3b studies regardless of PASI 100 response, for comparison.

Results Of those randomized to BKZ in phase 3 studies (excluding patients who switched to placebo; N=1,255), 775 (61.8%) achieved PASI 100 at Week 16 and 849 (67.6%) achieved PASI 100 at Week 48. Total BKZ exposure was 2,557.7 PY and 2,912.3 PY in Week 16 and Week 48 PASI 100 responders, respectively. Up to 4-year TEAE rates were 160.6/100 PY and 158.9/100 PY in Week 16 and Week 48 PASI 100 responders, respectively, and were similar to the overall BKZ-randomized population. Rates of serious and severe TEAEs in PASI 100 responders were also similar to those for overall BKZ-randomized patients. Similar to the overall BKZ-randomized population, the three most common TEAEs were upper respiratory tract infection (Week 16 PASI 100 responders: 25.7/100 PY; Week 48 PASI 100 responders: 26.8/100 PY), nasopharyngitis (Week 16: 12.1/100 PY; Week 48: 12.8/100 PY), and oral candidiasis (Week 16: 8.1/100 PY; Week 48: 8.1/100 PY). The majority of oral candidiasis events were mild/moderate (Week 16: 98.4%; Week 48: 98.8%) and few cases lead to discontinuation (Week 16: n=2; Week 48: n=1).

Conclusion Bimekizumab was well-tolerated through 4 years in patients who achieved complete skin clearance (PASI 100) at Week 16 and Week 48; the safety profile in these patients was consistent with the overall BKZ-randomized population in moderate to severe psoriasis.