口腔小分子酪氨酸激酶 2 和磷酸二酯酶 4 抑制剂治疗斑块状银屑病：网状荟萃分析。
Oral small-molecule tyrosine kinase 2 and phosphodiesterase 4 inhibitors in plaque psoriasis: a network meta-analysis.
机构信息
Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
出版信息
Front Immunol. 2023 Jun 2;14:1180170. doi: 10.3389/fimmu.2023.1180170. eCollection 2023.
BACKGROUND
Orally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy in plaque psoriasis. However, no previous articles evaluated the benefit and risk profile of TYK2 and PDE4 inhibitors in psoriasis.
OBJECTIVES
The objective of this study was to compare the efficacy and safety of oral small-molecule drugs, including TYK2 and PDE4 inhibitors, in treating moderate-to-severe plaque psoriasis.
METHODS
PubMed, Embase, and Cochrane library were searched for eligible randomized clinical trials (RCTs). Response rates for a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment score of 0 or 1 (PGA 0/1) were used for efficacy assessment. Safety was evaluated with the incidence of adverse events (AEs). A Bayesian multiple treatment network meta-analysis (NMA) was performed.
RESULTS
In total, 13 RCTs (five for TYK2 inhibitors and eight for PDE4 inhibitors) involving 5274 patients were included. The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. In addition, deucravacitinib (3 mg BID, 6 mg QD, 6 mg BID, and 12 mg QD), and ropsacitinib (400 mg QD) showed superior efficacy than apremilast (30 mg BID). In terms of safety, deucravacitinib or ropsacitinib at any dose did not lead to a higher incidence of AEs than apremilast (30 mg BID). The ranking analysis of efficacy revealed that deucravacitinib 12 mg QD and deucravacitinib 3 mg BID had the highest chance of being the most effective oral treatment, followed by deucravacitinib 6 mg BID and ropsacitinib 400 mg QD.
CONCLUSIONS
Oral TYK2 inhibitors demonstrated satisfactory performance in treating psoriasis, surpassing apremilast at certain doses. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859.
背景
口服小分子药物，包括酪氨酸激酶 2（TYK2）抑制剂和磷酸二酯酶 4（PDE4）抑制剂，是斑块状银屑病系统治疗的新候选药物。然而，以前没有文章评估 TYK2 和 PDE4 抑制剂在银屑病中的获益和风险特征。
目的
本研究旨在比较口服小分子药物（包括 TYK2 和 PDE4 抑制剂）在治疗中重度斑块状银屑病中的疗效和安全性。
方法
检索 PubMed、Embase 和 Cochrane 图书馆，以确定合格的随机临床试验（RCT）。采用银屑病面积和严重程度指数（PASI-75）和医生整体评估（PGA）评分从基线降低 75%的应答率来评估疗效。采用不良反应（AE）发生率评估安全性。采用贝叶斯多治疗网络荟萃分析（NMA）进行分析。
结果
共纳入 13 项 RCT（5 项针对 TYK2 抑制剂，8 项针对 PDE4 抑制剂），共涉及 5274 例患者。研究发现，德夸鲁单抗（除 3 mg QOD 外）、罗普司特利（200 和 400 mg QD）和阿普米司特（20 和 30 mg BID）的 PASI 和 PGA 应答率均高于安慰剂。此外，德夸鲁单抗（3 mg BID、6 mg QD、6 mg BID 和 12 mg QD）和罗普司特利（400 mg QD）的疗效优于阿普米司特（30 mg BID）。安全性方面，任何剂量的德夸鲁单抗或罗普司特利均未导致不良反应发生率高于阿普米司特（30 mg BID）。疗效的排名分析表明，德夸鲁单抗 12 mg QD 和德夸鲁单抗 3 mg BID 成为最有效的口服治疗药物的可能性最高，其次是德夸鲁单抗 6 mg BID 和罗普司特利 400 mg QD。
结论
口服 TYK2 抑制剂在治疗银屑病方面表现出令人满意的疗效，在某些剂量下优于阿普米司特。需要更多的大规模、长期研究来关注新型 TYK2 抑制剂。
系统评价注册
PROSPERO（ID：CRD42022384859），可从以下网址获取：https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859，标识符 CRD42022384859。
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