From the Center for Translational Research in Inflammatory Skin Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.); the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); the Icahn School of Medicine at Mount Sinai, New York (M.L.); the SKiN Centre for Dermatology, Probity Medical Research, Peterborough, and Queen's University, Kingston, ON (M.G.), and Dalhousie University, Halifax, NS (R.G.L.) - all in Canada; Yale University, New Haven, and Central Connecticut Dermatology Research, Cromwell - both in Connecticut (B.S.); Paul Sabatier University, Toulouse, France (C.P.); UCB Pharma, Brussels (D.D.C., V.V.); UCB Pharma, Raleigh, NC (C.M., C.C., L.P.); and the Oregon Medical Research Center, Portland (A.B.).
N Engl J Med. 2021 Jul 8;385(2):142-152. doi: 10.1056/NEJMoa2102383. Epub 2021 Apr 23.
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
In this phase 3b trial, we randomly assigned patients with moderate-to-severe plaque psoriasis, in a 1:1 ratio, to receive bimekizumab subcutaneously at a dose of 320 mg every 4 weeks or secukinumab subcutaneously at a dose of 300 mg weekly to week 4, followed by every 4 weeks to week 48. At week 16, patients receiving bimekizumab underwent rerandomization, in a 1:2 ratio, to receive maintenance dosing every 4 weeks or every 8 weeks to week 48. The primary end point was 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16. The primary analysis was first tested for the noninferiority of bimekizumab to secukinumab at a margin of -10 percentage points and then tested for superiority.
A total of 1005 patients were screened and 743 were enrolled; 373 patients were assigned to receive bimekizumab and 370 to receive secukinumab. At week 16, a total of 230 patients (61.7%) in the bimekizumab group and 181 (48.9%) in the secukinumab group had a 100% reduction from baseline in the PASI score (PASI 100) (adjusted risk difference, 12.7 percentage points; 95% confidence interval [CI], 5.8 to 19.6); bimekizumab was shown to be noninferior and superior to secukinumab (P<0.001 for noninferiority and superiority). At week 48, a total of 250 patients (67.0%) treated with bimekizumab had a PASI 100 response, as compared with 171 patients (46.2%) treated with secukinumab (adjusted risk difference, 20.9 percentage points; 95% CI, 14.1 to 27.7; P<0.001). At the week 4 time point, 265 patients (71.0%) in the bimekizumab group had 75% or greater reduction from baseline in the PASI score, as compared with 175 patients (47.3%) in the secukinumab group (adjusted risk difference, 23.7; 95% CI, 17.0 to 30.4; P<0.001). Oral candidiasis occurred more often with bimekizumab (72 patients, 19.3%) than with secukinumab (11 patients, 3.0%).
In patients with moderate-to-severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks but was associated with oral candidiasis (predominantly mild or moderate as recorded by the investigator). Longer and larger trials are required to determine the comparative effect and risks of interleukin-17 inhibitors in psoriasis. (Funded by UCB Pharma; BE RADIANT ClinicalTrials.gov number, NCT03536884.).
比美吉珠单抗是一种单克隆 IgG1 抗体，可选择性抑制白细胞介素-17A 和白细胞介素-17F。与单独选择性抑制白细胞介素-17A 的司库奇尤单抗相比，在中重度斑块型银屑病患者中，比美吉珠单抗的疗效和安全性尚未得到广泛研究。
在这项 3b 期试验中，我们以 1:1 的比例随机分配中重度斑块型银屑病患者，接受皮下注射比美吉珠单抗，剂量为 320mg，每 4 周一次，或皮下注射司库奇尤单抗，剂量为 300mg，每周一次，至第 4 周，随后每 4 周一次，至第 48 周。在第 16 周，接受比美吉珠单抗治疗的患者以 1:2 的比例重新随机分配，每 4 周或每 8 周维持剂量至第 48 周。主要终点是第 16 周时从基线水平下降 100%的银屑病面积和严重程度指数（PASI）评分。主要分析首先测试比美吉珠单抗相对于司库奇尤单抗的非劣效性，以 -10 个百分点为界，然后测试其优越性。
共有 1005 名患者接受了筛选，743 名患者入组；373 名患者被分配接受比美吉珠单抗治疗，370 名患者接受司库奇尤单抗治疗。在第 16 周，比美吉珠单抗组共有 230 名患者（61.7%）和司库奇尤单抗组 181 名患者（48.9%）达到 PASI 评分下降 100%（PASI 100）（调整后的风险差异为 12.7%；95%置信区间[CI]为 5.8 至 19.6）；比美吉珠单抗显示非劣效性和优于司库奇尤单抗（非劣效性和优越性均 P<0.001）。在第 48 周时，接受比美吉珠单抗治疗的 250 名患者（67.0%）有 PASI 100 反应，而接受司库奇尤单抗治疗的患者为 171 名（46.2%）（调整后的风险差异为 20.9%；95%CI 为 14.1 至 27.7；P<0.001）。在第 4 周时，比美吉珠单抗组有 265 名患者（71.0%）的 PASI 评分下降 75%或更多，而司库奇尤单抗组有 175 名患者（47.3%）（调整后的风险差异为 23.7%；95%CI 为 17.0 至 30.4；P<0.001）。口腔念珠菌病比美吉珠单抗（72 例，19.3%）更常见，而司库奇尤单抗（11 例，3.0%）。
在中重度银屑病患者中，与司库奇尤单抗相比，比美吉珠单抗治疗 16 周和 48 周后皮肤清除率更高，但与口腔念珠菌病相关（主要由研究者记录为轻度或中度）。需要更长和更大的试验来确定白细胞介素-17 抑制剂在银屑病中的比较效果和风险。（由 UCB Pharma 资助；BE RADIANT 临床试验.gov 编号，NCT03536884）。
