Schmitt J, Zhang Z, Wozel G, Meurer M, Kirch W
Department of Dermatology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
Br J Dermatol. 2008 Sep;159(3):513-26. doi: 10.1111/j.1365-2133.2008.08732.x. Epub 2008 Jul 9.
The comparative efficacy and tolerability of conventional and biologic treatments for moderate-to-severe plaque psoriasis are unknown.
To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) reporting efficacy of systemic treatments approved for moderate-to-severe psoriasis by means of the Psoriasis Area and Severity Index (PASI).
We identified relevant articles by systematic electronic searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as proportion of participants with >or= 75% decrease in PASI (PASI-75) at primary efficacy measurement (week 8-16). PASI-75 response rates of double-blind placebo-controlled trials were summarized as risk differences (RDs) and pooled using random effects models. Tolerability was assessed from rates of withdrawals and adverse events.
Twenty-four RCTs totalling 9384 patients were analysed qualitatively. Sixteen double-blind placebo-controlled trials were eligible for meta-analysis. Infliximab was significantly superior to all other interventions [RD 77%, 95% confidence interval (CI) 72-81%]. Adalimumab (RD 64%, 95% CI 61-68%) was superior to ciclosporin (RD 33%, 95% CI 13-52%), efalizumab (RD 24%, 95% CI 19-30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40-48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25-35%). Efalizumab was significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32-64%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters.
The efficacy of systemic agents approved for moderate-to-severe psoriasis differs considerably both within and between biologics and nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI-75 response. Published evidence questions regulatory guidelines that recommend biologics as second-line therapy for moderate-to-severe plaque psoriasis.
中度至重度斑块状银屑病的传统治疗与生物治疗的疗效及耐受性对比尚不清楚。
通过银屑病面积和严重程度指数（PASI），对已批准用于中度至重度银屑病的全身治疗的随机对照试验（RCT）进行系统评价和荟萃分析。
通过系统的电子检索（Cochrane图书馆、Medline、Embase、Scopus）确定相关文章。疗效定义为在主要疗效测量（第8 - 16周）时PASI降低≥75%（PASI - 75）的参与者比例。双盲安慰剂对照试验的PASI - 75缓解率总结为风险差异（RDs），并使用随机效应模型进行汇总。从撤药率和不良事件评估耐受性。
对总共9384例患者的24项RCT进行了定性分析。16项双盲安慰剂对照试验符合荟萃分析条件。英夫利昔单抗显著优于所有其他干预措施[RD 77%，95%置信区间（CI）72 - 81%]。阿达木单抗（RD 64%，95% CI 61 - 68%）优于环孢素（RD 33%，95% CI 13 - 52%）、依法利珠单抗（RD 24%，95% CI 19 - 30%）、每周两次50mg的依那西普（RD 44%，95% CI 40 - 48%）和每周两次25mg的依那西普（RD 30%，95% CI 25 - 35%）。依法利珠单抗的疗效显著低于富马酸酯（RD 48%，95% CI 32 - 64%）。因不良事件导致的撤药率在甲氨蝶呤和富马酸酯中最高。
已批准用于中度至重度银屑病的全身治疗药物在生物制剂和非生物制剂内部及之间的疗效差异很大。英夫利昔单抗疗效最佳，其次是阿达木单抗。接受英夫利昔单抗治疗的患者比接受安慰剂治疗的患者达到PASI - 75缓解的机会高77%。已发表的证据对将生物制剂推荐为中度至重度斑块状银屑病二线治疗的监管指南提出了质疑。
