托法替布治疗中、重度银屑病的疗效及安全性的系统评价和Meta分析

The Effect and Safety of Tofacitinib for Patients with Moderate to Severe Psoriasis: A Meta-Analysis of Randomized Controlled Trials

目的系统评价托法替布对中、重度银屑病的疗效及安全性。方法检索The Cochrane Library、PubMed、EMbase、Clinical Trials、CNKI、万方数据库、维普数据库和中国生物医学文献数据库(CBM),检索时间截至2018年5月,由2位研究者按纳入与排除标准筛选文献、提取资料并评价纳入研究的质量;采用Rev Man5. 3和Stata 12. 0软件进行Meta分析。结果最终纳入8项随机对照研究(RCT),共3 308例银屑病患者。Meta分析结果显示,与对照组相比,托法替布可显著降低患者银屑病面积和严重程度指数下降75%(RR 3. 27,95%CI:1. 79～5. 98,P=0. 000 1);银屑病面积和严重程度指数下降90%(RR 12. 61,95%CI:7. 66～20. 76,P <0. 000 01);医师整体评估(RR 4. 38,95%CI:3. 51～5. 47,P <0. 000 01)。安全性评价结果显示,与对照组相比,胆固醇水平增加(RR 2. 57,95%CI:1. 22～5. 38,P=0. 01);带状疱疹发生率增加(RR 3. 20,95%CI:0. 86～11. 91,P=0. 08)。结论托法替布临床使用相对安全有效,传统治疗药物效果较差的中重度银屑病患者可采用该药治疗。

OBJECTIVE To review systematically the effect and safety of tofacitinib for patients with moderate to severe psoriasis.METHODS Relevant studies were published until May 16,2018 were identified through The Cochrane Library,Pub Med,Embase,Clinical Trials.gov,CNKI,Wanfang,CBM and other web knowledge databases.Two reviewers independently screened literatures according to the inclusion and exclusion criteria,extracted data,and assessed the methodological quality of the included studies.Then we performed statistical analyses using the Review Manager 5.2 and Stata 12.0 software.RESULTS Eight randomized controlled trials that compared tofacitinib vs placebo were included in the study.The final Meta-analysis included a total of 3 308 patients with psoriasis.Tofacitinib was associated with reductions in psoriasis area and severity index 75%(RR 3.27,95%CI:1.79-5.98,P=0.000 1),psoriasis area and severity index 90%(RR 12.61,95%CI:7.66-20.76,P<0.000 01),physician’s global assessment(RR 4.38,95%CI:3.51-5.47,P<0.000 01).A safety analysis showed that tofacitinib increased the risk of hypercholesterolemia(RR 2.57,95%CI:1.22-5.38,P=0.01)and tended to associate with increasing the risk of herpes zoster(RR 3.20,95%CI:0.86-11.91,P=0.08).CONCLUSION Tofacitinib is effective and relatively safe for patients with psoriasis.Therefore,tofacitinib may be a promising treatment option for patients with moderate to severe psoriasis who had previously an inadequate response to the conventional synthetic treatment.