Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17A and IL-17F. We assessed the efficacy and safety of bimekizumab in patients with active psoriatic arthritis who were naive to biologic disease-modifying antirheumatic drugs (DMARDs). BE OPTIMAL was a 52-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, active reference (adalimumab) trial done at 135 sites (hospitals, clinics, doctors' offices, and research centres) in 14 countries. Eligible patients were 18 years or older with a documented diagnosis of adult-onset psoriatic arthritis that met the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening. Participants were randomly assigned with an interactive-voice and web-response system on the basis of a predetermined randomisation schedule (3:2:1, stratified by region and bone erosion number at baseline) to bimekizumab 160 mg every 4 weeks, placebo every 2 weeks, or the reference group (adalimumab 40 mg every 2 weeks), all administered subcutaneously. At week 16, patients randomly assigned to placebo switched to bimekizumab 160 mg every 4 weeks. The primary endpoint was the proportion of patients reaching 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses included all patients who were randomly assigned (intention-to-treat population); the safety analysis set comprised patients who received one or more doses of treatment. Data are presented to week 24 (preplanned analysis). This trial is registered at , . Between April 3, 2019, and Oct 25, 2021, 1163 patients were screened and 852 were randomly assigned to bimekizumab (n=431), placebo (n=281), and reference (adalimumab; n=140) groups. At week 16, significantly more patients receiving bimekizumab (189 [44%] of 431) reached ACR50 response versus placebo (28 [10%] of 281; odds ratio 7·1 [95% CI 4·6–10·9], p<0·0001; adalimumab 64 [46%] of 140). All secondary hierarchical endpoints were met. Treatment-emergent adverse events up to week 16 were reported in 258 [60%] of 431 patients receiving bimekizumab, 139 [49%] of 281 patients receiving placebo, and 83 [59%] of 140 patients receiving adalimumab. No deaths occurred. Bimekizumab treatment had superior improvements in joint, skin, and radiographic efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis who were naive to biologic DMARDs. The safety profile of bimekizumab, including the occurrence of fungal infections, was consistent with previous phase 3 studies in patients with plaque psoriasis, and with IL-17A inhibitors. UCB Pharma.

中文翻译：

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Bimekizumab 用于治疗未接受过生物治疗的银屑病关节炎患者：一项随机、双盲、安慰剂对照 3 期试验（BE OPTIMAL）

Bimekizumab 是一种单克隆 IgG1 抗体，可选择性抑制白细胞介素 (IL)-17A 和 IL-17F。我们评估了 bimekizumab 对未曾使用过生物缓解病情抗风湿药物 (DMARD) 的活动性银屑病关节炎患者的疗效和安全性。BE OPTIMAL 是一项为期 52 周、3 期、多中心、随机、双盲、安慰剂对照、主动参考（阿达木单抗）试验，在 14 个国家的 135 个地点（医院、诊所、医生办公室和研究中心）进行。符合条件的患者为 18 岁或以上，有成人发病银屑病关节炎诊断记录，且在筛选前至少 6 个月符合银屑病关节炎分类标准。根据预定的随机化时间表（3:2:1，按区域和基线骨侵蚀数量分层），参与者被随机分配到交互式语音和网络响应系统，每 4 周服用 bimekizumab 160 mg，每 2 周服用安慰剂周，或参考组（阿达木单抗 40 mg 每 2 周），全部皮下注射。第 16 周时，随机分配至安慰剂组的患者改为每 4 周服用 160 mg bimekizumab。主要终点是第 16 周时美国风湿病学会标准 (ACR50) 达到 50% 或更高改善的患者比例（无反应者插补）。疗效分析包括所有随机分配的患者（意向治疗人群）；安全性分析组包括接受一剂或多剂治疗的患者。数据提交至第 24 周（预先计划的分析）。该试验注册于 , 。2019年4月3日至2021年10月25日期间，对1163名患者进行了筛查，其中852名患者被随机分配至bimekizumab组（n=431）、安慰剂组（n=281）和参考组（阿达木单抗；n=140）组。在第 16 周，与安慰剂组（281 人中的 28 人 [10%]；比值比 7·1 [95% CI 4·6–10·9]）相比，接受 bimekizumab 治疗的患者（431 人中的 189 人 [44%]）达到 ACR50 缓解的人数显着增加。 p<0·0001；阿达木单抗 64 [46%] of 140)。所有次要分层终点均得到满足。截至第 16 周，接受 bimekizumab 的 431 名患者中有 258 名 [60%] 报告了治疗引起的不良事件，接受安慰剂的 281 名患者中有 139 名 [49%] 报告了治疗引起的不良事件，接受阿达木单抗的 140 名患者中有 83 名 [59%] 报告了治疗引起的不良事件。没有发生死亡事件。对于未曾接受过生物 DMARD 治疗的银屑病关节炎患者，与安慰剂相比，Bimekizumab 治疗在第 16 周时在关节、皮肤和放射学疗效结果方面具有显着改善。bimekizumab 的安全性（包括真菌感染的发生）与之前针对斑块型银屑病患者和 IL-17A 抑制剂进行的 3 期研究一致。UCB 制药公司。