小柯机器人

英国牛津大学风湿病学和肌肉骨骼疾病科Laura C Coates团队近期取得重要工作进展。他们对Bimekizumab治疗活动性银屑病关节炎患者和既往对TNFα抑制剂反应不足或不耐受患者的效果进行了分析，这是一项随机、双盲、安慰剂对照的3期试验（BE COMPLETE）。相关研究论文2022年12月6日在线发表于《柳叶刀》杂志上。

据介绍，Bimekizumab是一种单克隆IgG1抗体，可选择性地抑制白细胞介素（IL）-17F和IL-17A。这项研究比较了bimekizumab与安慰剂在16周内对活动性银屑病关节炎和既往对肿瘤坏死因子-α（TNFα）抑制剂反应不充分或不耐受的患者的疗效和安全性。

BE COMPLETE是一项3期、多中心、随机、双盲、安慰剂对照试验，在11个国家(澳大利亚、加拿大、捷克共和国、德国、匈牙利、意大利、日本、波兰、俄罗斯、英国和美国)的92个地点(包括医院、诊所和研究中心)进行。符合条件的患者年龄在18岁或以上，患有成人发病的银屑病关节炎(筛查前至少6个月符合银屑病关节炎分类标准)，既往对治疗银屑病关节炎或银屑病的一种或两种TNFα抑制剂反应不充分或不耐受。研究人员对活动性银屑病关节炎患者按区域和既往使用TNFα抑制剂进行了分层。患者被随机分配（2:1），根据预先确定的随机化计划，通过交互式语音和网络响应系统每4周皮下注射160毫克Bimekizumab或安慰剂。主要终点为第16周时，美国风湿病学会标准(ACR50)改善50%或以上的患者比例(无应答者归算)。在随机人群中进行疗效分析。安全性分析集包括接受一剂或多剂研究治疗的患者。该试验在ClinicalTrials.gov注册，NCT03896581，并已完成。

在2019年3月28日至2022年2月14日期间，对556名患者进行了筛查，400名患者被随机分配到每4周服用160 mg bimekizumab（n=267）或安慰剂（n=133）。在第16周时满足了主要终点和所有分级次要终点。267例接受bimekizumab治疗的患者中有116例(43%)达到ACR50，而133例接受安慰剂治疗的患者中有9例(7%)达到ACR50(校正后的优势比[OR] 11.1[95%置信区间，5.4至23.0]，p<0.0001)。接受bimekizumab治疗的176例至少影响3%体表面积的银屑病患者中，121例（69%）的银屑病面积和严重程度指数（PASI90）改善达到90%或以上，而接受安慰剂治疗的88例患者中有6例（7%）得到改善（校正后的OR为30.2[95%置信区间，12.4至73.9]，p<0.0001）。到第16周，接受bimekizumab治疗的267名患者中有108人（40%）和接受安慰剂治疗的132名患者中有44人（33%）报告了治疗突发不良事件。没有新的安全信号，也没有死亡。

研究结果表明，对TNFα抑制剂反应不足或不耐受的银屑病关节炎患者，与安慰剂相比，Bimekizumab治疗在第16周的关节和皮肤疗效结果上取得了更好的改善。bimekizumab的安全性与先前在斑块性银屑病患者中的3期研究以及IL-17A抑制剂的研究一致。

附：英文原文

Title: Bimekizumab in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α inhibitors: a randomised, double-blind, placebo-controlled, phase 3 trial (BE COMPLETE)

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

Issue&Volume: 2022-12-06

Abstract: Background

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A. This study compared the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α (TNFα) inhibitors.

Methods

BE COMPLETE was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial conducted across 92 sites (including hospitals, clinics, and research centres) in 11 countries (Australia, Canada, Czech Republic, Germany, Hungary, Italy, Japan, Poland, Russia, the UK, and the USA). Eligible patients were aged 18 years or older with adult-onset psoriatic arthritis (meeting the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening) with a history of inadequate response or intolerance to treatment with one or two TNFα inhibitors for either psoriatic arthritis or psoriasis. We stratified patients with active psoriatic arthritis by region and previous TNFα inhibitor use. Patients were randomly assigned (2:1) to receive subcutaneous bimekizumab 160 mg every 4 weeks or placebo by an interactive-voice and web-response system on the basis of a predetermined randomisation schedule. The primary endpoint was the proportion of patients with 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses were done in the randomised population. The safety analysis set comprised patients who received one or more doses of study treatment. This trial was registered at ClinicalTrials.gov, NCT03896581, and is completed.

Findings

Between March 28, 2019, and Feb 14, 2022, 556 patients were screened and 400 patients were randomly assigned to bimekizumab 160 mg every 4 weeks (n=267) or placebo (n=133). The primary and all hierarchical secondary endpoints were met at week 16. 116 (43%) of 267 patients receiving bimekizumab reached ACR50, compared with nine (7%) of 133 patients receiving placebo (adjusted odds ratio [OR] 11·1 [95% CI 5·4–23·0], p<0·0001). 121 (69%) of 176 patients with psoriasis affecting at least 3% body surface area at baseline who received bimekizumab reached 90% or greater improvement in the Psoriasis Area and Severity Index (PASI90), compared with six (7%) of 88 patients who received placebo (adjusted OR 30·2 [12·4–73·9], p<0·0001). Treatment-emergent adverse events up to week 16 were reported in 108 (40%) of 267 patients receiving bimekizumab and 44 (33%) of 132 patients receiving placebo. There were no new safety signals and no deaths.

Interpretation

Bimekizumab treatment led to superior improvements in joint and skin efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis and inadequate response or intolerance to TNFα inhibitors. The safety profile of bimekizumab was consistent with previous phase 3 studies in patients with plaque psoriasis, and studies of IL-17A inhibitors.

DOI: 10.1016/S0140-6736(22)02303-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02303-0/fulltext

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