生物制剂在类风湿关节炎进展损害中的作用：来自随机临床试验数据的间接比较。
The role of biologic agents in damage progression in rheumatoid arthritis: indirect comparison of data coming from randomized clinical trials.
机构信息
Division of Rheumatology, University of Milan, Via G. Pini, 9 20122 Milan, Italy.
出版信息
Ther Adv Musculoskelet Dis. 2012 Aug;4(4):213-23. doi: 10.1177/1759720X12449082.
OBJECTIVES
All biologic agents approved for the treatment of rheumatoid arthritis (RA) have been tested versus methotrexate (MTX) for efficacy on damage progression in several randomized clinical trials (RCTs), but direct head-to-head comparisons have never been conducted. The purpose of this investigation is to analyse data coming from main RA RCTs and to perform an indirect comparison.
METHODS
A systematic review of literature from 1988 to 2011 was conducted. Only randomized, double-blind, controlled, comparative trials, with evaluation of radiographic progression were included. The radiographic score was standardized and mean difference in the percentage of the annual radiographic progression rate was used as the effect measure. Heterogeneity between studies was estimated by I(2) test. For each trial, the effect was plotted according to its standard error in a funnel plot.
RESULTS
Of 44 potentially relevant trials, 12 RCTs were included in the study. In order to optimize RCTs comparison, studies were stratified in early and late RA group. Main population characteristics were similar in both early and late RA groups, whereas the standardized baseline radiographic score value significantly differs among trials in both early (range 2.7-21.9) and late (range 23.46-75) RA groups. The standardized annual estimated progression is similar across the late RA group. Strong evidence of heterogeneity (I(2) = 97%, p = 0.00001) but no asymmetry of the funnel plot was observed in the early RA group. Total mean difference was -16.28 (95% confidence interval [CI] -24.42 to -8.14). For the late RA group a random model was used (I(2) = 99%, p = 0.00001) and a total mean difference of -39.25 (95% CI -53.77 to -24.73) was found.
CONCLUSIONS
All biologic agents provide a favourable effect on disease progression both in early and late RA. The significant heterogeneity among various RCTs did not allow an effective comparison of the performance of biologic agents in each study.
目的
所有已获批用于治疗类风湿关节炎（RA）的生物制剂均已在多项随机临床试验（RCT）中与甲氨蝶呤（MTX）进行了疗效比较，以评估对损害进展的影响，但从未进行过直接的头对头比较。本研究旨在分析主要 RA RCT 的数据并进行间接比较。
方法
进行了 1988 年至 2011 年文献的系统回顾。仅纳入了随机、双盲、对照、比较试验，并评估了放射学进展情况。放射学评分进行了标准化，将每年放射学进展率的百分比差异作为效应测量值。通过 I²检验估计研究间的异质性。对于每个试验，根据其标准误在漏斗图中绘制效应。
结果
在 44 项潜在相关试验中，有 12 项 RCT 纳入了本研究。为了优化 RCT 比较，将研究分为早期和晚期 RA 组。主要人群特征在早期和晚期 RA 组中相似，而在早期 RA 组（范围 2.7-21.9）和晚期 RA 组（范围 23.46-75）中，标准化基线放射学评分值在各试验之间存在显著差异。晚期 RA 组的标准化年估计进展相似。在早期 RA 组中观察到高度异质性（I²=97%，p=0.00001）但漏斗图无明显不对称性。总平均差异为-16.28（95%置信区间[CI] -24.42 至-8.14）。对于晚期 RA 组，使用了随机模型（I²=99%，p=0.00001），发现总平均差异为-39.25（95%CI -53.77 至-24.73）。
结论
所有生物制剂在早期和晚期 RA 中均对疾病进展产生有利影响。各 RCT 之间存在显著的异质性，使得无法有效地比较每种研究中生物制剂的表现。
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