From the Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester National Institute for Health Research Biomedical Research Centre, University of Manchester, Manchester, United Kingdom (R.B.W.); Oregon Medical Research Center, Portland (A.B.); Psoriasis Treatment Center of Central New Jersey, East Windsor (J.B.); Probity Medical Research and K. Papp Clinical Research, Waterloo, ON (K.A.P.), and Dalhousie University, Halifax, NS (R.G.L.) - both in Canada; Dermatology Institute and Skin Care Center, Santa Monica, CA (P.Y.); the Division of Dermatology, David Geffen School of Medicine at University of California, Los Angeles (P.Y.), and the Department of Dermatology, Keck School of Medicine, University of Southern California (A.A.) - both in Los Angeles; UCB Pharma, Brussels (V.V., D.D.C.); UCB Pharma, Raleigh, NC (C.C., L.P., N.C.); and the Center for Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (K.R.).
N Engl J Med. 2021 Jul 8;385(2):130-141. doi: 10.1056/NEJMoa2102388. Epub 2021 Apr 23.
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the tumor necrosis factor inhibitor adalimumab in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
We randomly assigned patients with moderate-to-severe plaque psoriasis in a 1:1:1 ratio to receive subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at a dose of 320 mg every 4 weeks for 16 weeks, then every 8 weeks for weeks 16 to 56; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56. The primary end points were a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI 90 response; PASI scores range from 0 to 72, with higher scores indicating worse disease) and an Investigator's Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (scores range from 0 [clear skin] to 4 [severe disease]), at week 16. The analysis of the primary end points tested noninferiority at a margin of -10 percentage points and then tested for superiority.
A total of 614 patients were screened, and 478 were enrolled; 158 patients were assigned to receive bimekizumab every 4 weeks, 161 to receive bimekizumab every 4 weeks and then every 8 weeks, and 159 to receive adalimumab. The mean age of the patients was 44.9 years; the mean PASI score at baseline was 19.8. At week 16, a total of 275 of 319 patients (86.2%) who received bimekizumab (both dose groups combined) and 75 of 159 (47.2%) who received adalimumab had a PASI 90 response (adjusted risk difference, 39.3 percentage points; 95% confidence interval [CI], 30.9 to 47.7; P<0.001 for noninferiority and superiority). A total of 272 of 319 patients (85.3%) who received bimekizumab and 91 of 159 (57.2%) who received adalimumab had an IGA score of 0 or 1 (adjusted risk difference, 28.2 percentage points; 95% CI, 19.7 to 36.7; P<0.001 for noninferiority and superiority). The most common adverse events with bimekizumab were upper respiratory tract infections, oral candidiasis (predominantly mild or moderate as recorded by the investigator), hypertension, and diarrhea.
In this 56-week trial, bimekizumab was noninferior and superior to adalimumab through 16 weeks in reducing symptoms and signs of plaque psoriasis but was associated with a higher frequency of oral candidiasis and diarrhea. Longer and larger trials are required to determine the efficacy and safety of bimekizumab as compared with other agents in the treatment of plaque psoriasis. (Funded by UCB Pharma; BE SURE ClinicalTrials.gov number, NCT03412747.).
Bimekizumab 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。与肿瘤坏死因子抑制剂阿达木单抗相比，bimekizumab 治疗中度至重度斑块型银屑病患者的疗效和安全性尚未得到广泛研究。
我们以 1:1:1 的比例随机分配中度至重度斑块型银屑病患者，分别接受皮下注射 bimekizumab 320mg，每 4 周一次，共 56 周；bimekizumab 320mg，每 4 周一次，共 16 周，然后每 8 周一次，共 16 至 56 周；或皮下注射阿达木单抗 40mg，每 2 周一次，共 24 周，然后每 4 周一次，共 56 周。主要终点是从基线到第 16 周时 PASI 评分（PASI 90 反应；PASI 评分范围为 0 至 72，分数越高表示疾病越严重）和医师整体评估（IGA）评分均降低 90%或更多，分别为 0 或 1，代表皮肤清晰或几乎清晰（评分范围为 0 [皮肤清晰]至 4 [严重疾病]）。主要终点分析在 -10 个百分点的边缘处检验非劣效性，然后检验优越性。
共有 614 名患者接受筛查，478 名患者入选；158 名患者接受 bimekizumab 每 4 周一次，161 名患者接受 bimekizumab 每 4 周一次，然后每 8 周一次，159 名患者接受阿达木单抗。患者的平均年龄为 44.9 岁；基线时平均 PASI 评分为 19.8。第 16 周时，接受 bimekizumab（两组剂量）的 319 名患者中的 275 名（86.2%）和接受阿达木单抗的 159 名患者中的 75 名（47.2%）达到 PASI 90 反应（调整后的风险差异，39.3 个百分点；95%置信区间[CI]，30.9 至 47.7；P<0.001 用于非劣效性和优越性）。接受 bimekizumab 的 319 名患者中的 272 名（85.3%）和接受阿达木单抗的 159 名患者中的 91 名（57.2%）达到 IGA 评分 0 或 1（调整后的风险差异，28.2 个百分点；95%CI，19.7 至 36.7；P<0.001 用于非劣效性和优越性）。接受 bimekizumab 的最常见不良事件是上呼吸道感染、口腔念珠菌病（主要是研究者记录的轻度或中度）、高血压和腹泻。
在这项 56 周的试验中，bimekizumab 在第 16 周时通过减少斑块型银屑病的症状和体征，与阿达木单抗相比非劣效且具有优越性，但与口腔念珠菌病和腹泻的发生率较高有关。需要进行更长和更大规模的试验来确定 bimekizumab 与其他药物在治疗斑块型银屑病方面的疗效和安全性。（由 UCB Pharma 资助；BE SURE 临床试验。gov 编号，NCT03412747。）
