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中重度斑块状银屑病生物制剂治疗的疗效比较:调整参考组应答差异的网络荟萃分析。

Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response.

机构信息

Analysis Group, Inc., 111 Huntington Avenue, 10th floor, Boston, MA, 02199, U.S.A.

出版信息

Br J Dermatol. 2015 Feb;172(2):504-12. doi: 10.1111/bjd.13437. Epub 2015 Jan 21.

Abstract

BACKGROUND

Multiple biological therapies are approved for the treatment of moderate-to-severe psoriasis.

OBJECTIVES

To assess the short-term efficacy of biological treatments for moderate-to-severe psoriasis via a network meta-analysis that adjusts for reference arm response rates.

METHODS

Fifteen randomized trials of biological treatments for moderate-to-severe psoriasis were identified. Rates of response, assessed as 50%, 75% and 90% reductions in the Psoriasis Area and Severity Index (PASI), were compared using a network meta-analysis. To account for variation across trials, the model was adjusted for placebo responses, the relevance of which was assessed by testing its statistical significance, impact on model fit, and extent to which lack of adjustment confounded the efficacy estimates for biologics.

RESULTS

Psoriasis Area and Severity Index 75 response rates for placebo arms ranged from 1·8% to 18·9%. The probability of achieving a PASI 75 response was 80·5% [95% credible interval (CrI) 74·8-85·7] with infliximab 5 mg kg(-1) ; 72·5% (95% CI 66·1-78·3) with ustekinumab 90 mg; 67·5% (95% CI 60·7-73·9) with ustekinumab 45 mg; 66·2% (95% CI 57·3-73·3) with adalimumab 40 mg; 51·9% (95% CI 45·7-58·4) with etanercept 50 mg; and 38·0% (95% CI 31·6-45·1) with etanercept 25 mg. Infliximab had the highest PASI 75 response. Adalimumab and both ustekinumab doses had significantly higher PASI 75 responses than both etanercept doses. There were no significant differences among adalimumab and ustekinumab doses.

CONCLUSIONS

A model adjusted for reference arm response rates was found to fit clinical trial data significantly better than unadjusted models.

摘要

背景

有多种生物疗法获批用于治疗中重度银屑病。

目的

通过网络荟萃分析评估中重度银屑病生物疗法的短期疗效,该分析调整了参考臂的应答率。

方法

共确定了 15 项中重度银屑病生物疗法的随机试验。采用网络荟萃分析比较了应答率(以银屑病面积和严重程度指数(PASI)降低 50%、75%和 90%评估)。为了考虑到试验间的差异,模型根据安慰剂的应答情况进行了调整,通过检验其统计学意义、对模型拟合的影响以及缺乏调整对生物制剂疗效估计的混淆程度来评估其相关性。

结果

安慰剂组 PASI 75 应答率范围为 1.8%至 18.9%。接受英夫利昔单抗 5mg/kg、乌司奴单抗 90mg、乌司奴单抗 45mg、阿达木单抗 40mg、依那西普 50mg 和依那西普 25mg 治疗的患者获得 PASI 75 应答的概率分别为 80.5%(95%可信区间[CrI]74.8-85.7)、72.5%(95% CrI 66.1-78.3)、67.5%(95% CrI 60.7-73.9)、66.2%(95% CrI 57.3-73.3)、51.9%(95% CrI 45.7-58.4)和 38.0%(95% CrI 31.6-45.1)。英夫利昔单抗的 PASI 75 应答最高。阿达木单抗和两种乌司奴单抗剂量的 PASI 75 应答显著高于两种依那西普剂量。阿达木单抗和乌司奴单抗两种剂量之间无显著差异。

结论

与未调整模型相比,调整参考臂应答率的模型发现更能拟合临床试验数据。

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