Bimekizumab efficacy and safety through 3 years in patients with moderate-to-severe plaque psoriasis: long-term results from the BE RADIANT phase IIIb trial open-label extension period
Richard B. Warren, Mark Lebwohl, Diamant Thaçi, Melinda Gooderham, Andreas Pinter, C. Paul, Paolo Gisondi, Balint Szilagyi, Katy White, Delphine Deherder, Fabienne Staelens, Jérémy Lambert, Bruce Strober
Abstract
BACKGROUND: Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F. BE RADIANT was the first phase III trial to investigate switching from selective inhibition of IL-17A to dual inhibition of IL-17A and IL-17F. Bimekizumab has previously shown superior achievement of complete skin clearance [100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100)] vs. secukinumab through 48 weeks. Switching from secukinumab to bimekizumab resulted in improved clinical responses. Over 2 years, no new safety signals were observed. OBJECTIVES: To report the 3-year efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis receiving continuous bimekizumab or switching from secukinumab after 1 year. METHODS: The BE RADIANT phase IIIb randomized controlled trial had a 48-week double-blinded period, in which patients received bimekizumab [320 mg every 4 weeks (Q4W)] or secukinumab (300 mg weekly to week 4, then Q4W). At week 16, patients randomized to bimekizumab underwent re-randomization to receive Q4W or Q8W maintenance dosing. From week 48 onward (open-label extension), all received bimekizumab. RESULTS: In total, 336 patients randomized to bimekizumab and 318 randomized to secukinumab at baseline entered the open-label extension. More patients randomized to bimekizumab achieved PASI 100 (modified nonresponder imputation) at year 1 (74.9%) vs. those randomized to secukinumab (52.8%). PASI 100 response rates were maintained over 3 years in patients treated with bimekizumab (68.8%) and increased in those randomized to secukinumab switching to bimekizumab (68.8%). Bimekizumab was well tolerated to 3 years. In patients who received ≥ 1 bimekizumab dose, the most common treatment-emergent adverse events (TEAEs) over 3 years were nasopharyngitis, oral candidiasis and upper respiratory tract infection (exposure-adjusted incidence rates 12.2, 10.0 and 5.5/100 patient-years, respectively). Rates of TEAEs of interest, including serious infections, inflammatory bowel disease, and suicidal ideation and behaviour, did not increase with longer exposure to bimekizumab from 1 to 3 years. CONCLUSIONS: More than two-thirds of patients randomized to bimekizumab and those who switched from secukinumab to bimekizumab achieved and maintained complete skin clearance over 3 years of treatment. Over 3 years, bimekizumab was well tolerated and TEAE rates did not increase with longer exposure. TRIAL REGISTRATION: NCT03536884.