英国格拉斯哥大学Iain B McInnes团队研究了比美吉珠单抗治疗生物治疗不敏感的银屑病关节炎患者的疗效与安全性。相关论文于2022年12月5日发表在《柳叶刀》杂志上。

比美吉珠单抗是一种选择性抑制白介素（IL）-17A和IL-17F的单克隆IgG1抗体。研究组评估了比美吉珠单抗在患有活动性银屑病关节炎的患者中的有效性和安全性，这些患者最初使用生物疾病修饰抗风湿药物（DMARDs）。

研究组在14个国家的135个地点（医院、诊所、医生办公室和研究中心）进行了一项为期52周、3期、多中心、随机、双盲、安慰剂对照、主动参照（阿达木单抗）试验。符合条件的患者为18岁及以上，在筛选前至少6个月内有成年发病银屑病关节炎的诊断记录，符合银屑病关节炎分类标准。

根据预先确定的随机化计划（3:2:1，根据基线时的区域和骨侵蚀数量分层），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160 mg比美吉珠单抗，每2周服用安慰剂，或参照组（每2周服40 mg阿达木单抗），全部皮下给药。第16周，随机分配至安慰剂组的患者每4周服用160 mg比美吉珠单抗。

主要终点是患者在第16周达到美国风湿病学会标准（ACR50）50%或以上改善的比例（无应答者插补）。疗效分析包括随机分配的所有患者（意向治疗人群）；安全性分析集包括接受一种或多种剂量治疗的患者。数据显示在第24周（预先计划的分析）。

2019年4月3日至2021年10月25日，研究组对1163名患者进行了筛查，852名患者被随机分为比美吉珠单抗组（n=431）、安慰剂组（n=281）和对照组（阿达木单抗组；n=140）。在第16周，比美吉珠单抗组患者431人中有189人（44%）达到ACR50应答，显著高于安慰剂组（281人中有28人[10%]），优势比为7.1；阿达木单抗组140人中有64人（46%）。

所有次要层次终结点均满足。截至第16周，比美吉珠单抗组431名患者中有258名（60%）出现了治疗突发性不良事件，281名接受安慰剂治疗的患者有139名（49%），140名接受阿达木单抗治疗的患者中有83名（59%）。没有死亡事件发生。

研究结果表明，在未接受生物DMARDs治疗的银屑病关节炎患者中，与安慰剂相比，比美吉珠单抗治疗在第16周的关节、皮肤和影像学疗效结局方面有显著改善。比美吉珠单抗的安全性，包括真菌感染的发生，与之前在斑块型银屑病患者和IL-17A抑制剂中进行的3期研究一致。

附：英文原文

Title: Bimekizumab in patients with psoriatic arthritis, naive to biologic treatment: a randomised, double-blind, placebo-controlled, phase 3 trial (BE OPTIMAL)

Author: Iain B McInnes, Akihiko Asahina, Laura C Coates, Robert Landewé, Joseph F Merola, Christopher T Ritchlin, Yoshiya Tanaka, Laure Gossec, Alice B Gottlieb, Richard B Warren, Barbara Ink, Deepak Assudani, Rajan Bajracharya, Vishvesh Shende, Jason Coarse, Philip J Mease

Issue&Volume: 2022-12-05

Abstract:

Background

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).

Methods

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 ClinicalTrials.gov, NCT03895203.

Findings

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.

Interpretation

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.

DOI: 10.1016/S0140-6736(22)02302-9

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02302-9/fulltext