Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis - A Meta-Analysis

ObjectiveWe did a systematic review of studies comparing discontinuation of tumor necrosis factor alpha (TNF) antagonists in rheumatoid arthritis (RA) patients, pooled hazard ratios and assessed clinical and methodological heterogeneity.MethodsWe searched MEDLINE and EMBASE until June 2015 for pairwise hazard ratios for discontinuing infliximab, etanercept, and adalimumab from cohorts of RA patients. Hazard ratios were pooled using inverse variance weighting and random effects estimates of the combined hazard ratio were obtained. Clinical and methodological heterogeneity was assessed using the between-subgroup I-square statistics and meta-regression.ResultsTwenty-four unique studies were eligible and large heterogeneity (I-square statistics > 50%) was observed in all comparisons. Type of data, location, and order of treatment (first or second line) modified the magnitude and direction of discontinuation comparing infliximab with either adalimumab or etanercept; however, some heterogeneity remained. No effect modifier was identified when adalimumab and etanercept were compared.ConclusionHeterogeneity in studies comparing discontinuation of TNF antagonists in RA is partially explained by type of data, location, and order of treatment. Pooling hazard ratios for discontinuing TNF antagonists is inappropriate because largely unexplained heterogeneity was demonstrated when random effect estimates were calculated.

研究目的：本研究针对类风湿关节炎（RA）患者停用肿瘤坏死因子α（TNF-α）拮抗剂的对比研究开展系统综述，合并风险比（hazard ratios）并评估临床与方法学异质性。
研究方法：我们检索了截至2015年6月的MEDLINE与EMBASE数据库，获取类风湿关节炎患者队列中停用英夫利昔单抗（infliximab）、依那西普（etanercept）与阿达木单抗（adalimumab）的配对风险比。采用逆方差加权法合并风险比，并得到合并风险比的随机效应估计值。通过亚组间I²统计量（I-square statistics）与Meta回归分析评估临床及方法学异质性。
研究结果：最终纳入24项独立研究，所有对比组均观察到显著异质性（I²统计量>50%）。在英夫利昔单抗与阿达木单抗或依那西普的停药对比中，数据类型、研究地点与治疗线序（一线或二线）会影响停药风险比的大小与方向，但仍存在部分未解释的异质性。而阿达木单抗与依那西普的对比未发现明确的效应修饰因子。
研究结论：类风湿关节炎患者停用肿瘤坏死因子α拮抗剂相关对比研究中的异质性，可部分由数据类型、研究地点与治疗线序加以解释。由于在计算随机效应估计值时仍存在大量未阐明的异质性，因此合并肿瘤坏死因子α拮抗剂停药相关的风险比并不恰当。