Supplementary Material for: Efficacy and safety of newer topical therapies in psoriasis: A systematic review and network meta-analysis

Introduction: Psoriasis is a chronic immune-mediated skin disease. Several clinical trials have studied some topical drugs aiming at new therapeutic targets. However,the comparative efficacy and safety of different concentrations and frequencies of newer topical drugs for psoriasis remain unclear.The aim of our study is to assess the comparative efficacy and safety of some newer topical treatments in patients with psoriasis. Methods: A systematic review and network meta-analysis (NMA) was conducted using eligible randomized controlled trials (RCTs). Treatments included topical therapeutic aryl hydrocarbon receptor(AhR)-modulating agent(TAMA), topical phosphodiesterase type 4 (PDE‑4) inhibitors and topical janus kinase-signal transducer and activator of transcription(JAK-STAT) inhibitors. The primary efficacy assessment criteria was the proportion of patients’ achieving Physician’s Global Assessment 0/1 (PGA response). Secondary criteria was≥75 % reductions in Psoriasis Area and Severity Index (PASI 75). Adverse events (AEs) to represent the safety were also summarized. Results: Among 6 including newer topical drugs, odds of achieving both PGA response and PASI 75 were higher with all regimen of TAMA and roflumilast cream versus vehicle. In terms of safety outcomes, odds of AEs was also higher with all regimen of TAMA. There were no statistically significant differences between topical JAK-STAT inhibitors and vehicle for any outcome, except ruxolitinib ointment 1% once daily (QD). Conclusion: TAMA had a good therapeutic effect on plaque psoriasis but a relatively low treatment safety. Roflumilast cream had both promising efficacy and higher safety.

引言：银屑病是一种慢性免疫介导性皮肤病。目前已有多项临床试验针对新型治疗靶点开发外用药物，但不同浓度、不同给药频次的新型外用药物治疗银屑病的相对疗效与安全性仍未明确。本研究旨在评估各类新型外用疗法治疗银屑病患者的相对疗效与安全性。
方法：本研究纳入符合标准的随机对照试验（randomized controlled trial, RCT），开展系统评价与网络meta分析（network meta-analysis, NMA）。纳入的治疗方案包括：外用芳基烃受体（aryl hydrocarbon receptor, AhR）调节剂（TAMA）、外用磷酸二酯酶4型（phosphodiesterase type 4, PDE-4）抑制剂，以及外用Janus激酶-信号转导与转录激活因子（Janus kinase-signal transducer and activator of transcription, JAK-STAT）抑制剂。本研究的主要疗效评价指标为患者达到医师整体评估0/1分的比例（PGA应答率）；次要疗效指标为银屑病面积与严重程度指数较基线改善≥75%（PASI 75）。同时汇总不良事件（adverse events, AEs）以评估治疗安全性。
结果：在纳入的6种新型外用药物中，相较于赋形剂对照组，所有TAMA给药方案以及罗氟司特乳膏均能提升患者达到PGA应答率与PASI 75的比值比。安全性结局方面，所有TAMA给药方案的不良事件发生风险同样高于对照组。除1%鲁索替尼乳膏每日一次（once daily, QD）给药方案外，外用JAK-STAT抑制剂与赋形剂对照组在各项结局指标上均无统计学显著性差异。
结论：TAMA对斑块状银屑病具有良好的治疗效果，但治疗安全性相对较低。罗氟司特乳膏兼具优异的疗效与较高的安全性。