2020年3月13日出版的《柳叶刀》杂志发布了美国华盛顿大学Philip J Mease研究小组的最新成果，他们对古塞库单抗治疗生物制剂初治的活动期银屑病关节炎的疗效和安全性进行了分析。

白细胞介素23（IL-23）/ T-辅助17细胞途径与银屑病关节炎的发病机制有关。古塞库单抗是一种特异性结合IL-23 p19亚基的IL-23抑制剂，在2期研究中可安全有效地改善银屑病关节炎。

2017年7月13日至2018年8月3日，这项临床3期、双盲、安慰剂对照研究在亚洲、欧洲和北美的13个国家/地区的118个地点进行。研究组共招募了741名标准治疗无效、生物制剂初治的活动期银屑病关节炎患者。

将这些患者按1：1：1随机分组，其中246名接受每4周一次皮下注射古塞库单抗100mg；248名接受第0、4周皮下注射古塞库单抗100mg，之后每8周注射一次；247名接受安慰剂治疗。主要终点为第24周时美国风湿病学院20%改善（ACR20）。

共有716名患者一直治疗至第24周。4周组有64%的患者达到主要终点，8周组有64%，均显著高于安慰剂组（33%）。至第24周，4周组中严重不良事件发生率为3%（包括3例严重感染），8周组为1%（1例严重感染），安慰剂组为3%（1例严重感染）。各组均无死亡事件发生。

古塞库单抗是一种通过结合细胞因子p19亚基特异性抑制IL-23的人源单克隆抗体，对生物制剂初治的银屑病关节炎患者安全有效。

附：英文原文

Title: Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial

Author: Philip J Mease, Proton Rahman, Alice B Gottlieb, Alexa P Kollmeier, Elizabeth C Hsia, Xie L Xu, Shihong Sheng, Prasheen Agarwal, Bei Zhou, Yanli Zhuang, Désirée van der Heijde, Iain B McInnes

Issue&Volume: 2020-03-13

Abstract: BackgroundThe interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis.MethodsThis phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting).FindingsFrom July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57–70]) and every 8 weeks group (159 [64%] of 248 [58–70]) than in the placebo group (81 [33%] of 246 [27–39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22–39] for the every 4 weeks group and 31% [23–40] for the every 8 weeks group; both p<0·0001). Up to week 24, serious adverse events occurred in eight (3%) of 245 patients receiving guselkumab every 4 weeks (three serious infections), three (1%) of 248 receiving guselkumab every 8 weeks (one serious infection), and seven (3%) of 246 receiving placebo (one serious infection). No deaths occurred.InterpretationGuselkumab, a human monoclonal antibody that specifically inhibits IL-23 by binding the cytokine's p19 subunit, was efficacious and demonstrated an acceptable benefit–risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics. These data support the use of selective inhibition of IL-23 to treat psoriatic arthritis.

DOI: 10.1016/S0140-6736(20)30263-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30263-4/fulltext