Supplementary Material for: Th17 Inhibitors in Active Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

<b><i>Background:</i></b> Several biologics targeting the Th17 pathway have been developed for the treatment of psoriatic arthritis (PsA), a disabling disease with moderate response and an increased incidence of serious infections to first-line biologics (TNF-α antagonists). Th17 inhibitors could replace TNF-α antagonists as first-line biologic agents. We determined the overall treatment effect of Th17 pathway inhibitors compared to placebo or active control on American College of Rheumatology (ACR) 20 response at week 12 (primary objective), risk of infections, discontinuation of treatment due to adverse events, and serious adverse events during the placebo-controlled period (12-24 weeks) in adults with active PsA in published randomized controlled trials. <b><i>Methods:</i></b> The SCOPUS database was searched. The Cochrane risk of bias tool was used for assessing quality. The pooled relative risk (RR) was derived from random effects models. <b><i>Results:</i></b> Seven randomized controlled trials were included which randomized 1,718 patients to Th17 inhibitors and 840 to placebo. Patients treated with Th17 inhibitors had an RR of 2.04 (95% CI: 1.79-2.33; <i>p</i> &lt; 0.001) for achieving an ACR20 response at week 12 (I² = 0%; <i>p</i> = 0.89) compared to placebo-treated patients. There was no evidence of publication bias. The result was consistent for study phase and outcome (ACR50/70), mechanism of action and TNF-α naivety. RR of infections was 1.06 (0.91-1.23), that of candida infections was 3.35 (0.75-14.95), that of serious adverse events was 0.82 (0.42-1.59) and that of discontinuation of treatment was 0.54 (0.31-0.93) among treated versus placebo subjects. No incident cases of tuberculosis were reported. <b><i>Conclusion:</i></b> In patients with active PsA, biologics targeting the Th17 axis produce a clinically significant improvement in joint disease activity with acceptable safety and tolerability for short-term treatment compared to placebo.

**研究背景**：已有多款靶向Th17通路的生物制剂被开发用于治疗银屑病关节炎（psoriatic arthritis, PsA）——这是一类致残性疾病，一线生物制剂（肿瘤坏死因子α拮抗剂，TNF-α antagonists）的临床应答率中等，且严重感染的发生率显著升高。Th17抑制剂有望替代TNF-α拮抗剂成为银屑病关节炎的一线生物治疗药物。本研究旨在通过纳入已发表的随机对照试验，评估活动性银屑病关节炎成人患者中，与安慰剂或阳性对照药物相比，Th17通路抑制剂在12周时达到美国风湿病学会（American College of Rheumatology, ACR）20%应答标准（ACR20，主要研究结局）的总体治疗效应，同时分析安慰剂对照期（12~24周）内的感染风险、因不良事件停药率及严重不良事件发生情况。
**研究方法**：检索SCOPUS数据库，采用Cochrane偏倚风险评估工具对纳入研究的质量进行评价，通过随机效应模型计算合并相对危险度（relative risk, RR）。
**研究结果**：共纳入7项随机对照试验，涉及1718例接受Th17抑制剂治疗的患者及840例接受安慰剂治疗的患者。与安慰剂组相比，Th17抑制剂组患者在12周时达到ACR20应答的合并相对危险度为2.04（95%置信区间：1.79~2.33；p<0.001），研究间异质性极低（I²=0%；p=0.89）。未发现明确的发表偏倚证据。该研究结果在研究阶段、结局指标（ACR50/70）、作用机制以及TNF-α初治患者亚组中均保持一致。治疗组与安慰剂组相比，感染的合并RR为1.06（0.91~1.23），念珠菌感染的合并RR为3.35（0.75~14.95），严重不良事件的合并RR为0.82（0.42~1.59），因不良事件停药的合并RR为0.54（0.31~0.93）。本研究未报告结核感染病例。
**研究结论**：与安慰剂相比，靶向Th17通路的生物制剂可显著改善活动性银屑病关节炎患者的关节疾病活动度，且短期治疗的安全性及耐受性良好。