Meta-analysis of treatment termination rates among rheumatoid arthritis patients receiving disease-modifying anti-rheumatic drugs
Meta-analysis of treatment termination rates among rheumatoid arthritis patients receiving disease-modifying anti-rheumatic drugs
复制标题
DOI：
10.1093/rheumatology/39.9.975
复制
发表时间：
2000-09-01
期刊：
影响因子：
5.5
通讯作者：
Bombardier, C
中科院分区：
文献类型：
--
作者：
Maetzel, A;Wong, A;Bombardier, C
Objective.总结甲氨蝶呤（MTX）、金霉素（GST）、柳氮磺胺吡啶（SSZ）和羟氯喹（HCQ）治疗类风湿关节炎（RA）的观察性研究和随机对照试验（RCTs）中关于停药率的证据。使用两个独立的Medline检索来检索1966年至1997年间发表的相关研究。那些披露了退出药物的患者数量信息的人被保留。然后使用精算生存估计值计算治疗后的累积生存概率，并使用对数秩、Wilcoxon和考克斯比例风险检验检验差异。共有159项研究提供了退出信息，一般或由于无效或毒性而退出的患者数量可从110项研究中提取，涉及142个治疗组（MTX，48; GST，56; SSZ，22; HCQ，16）。HCQ的数据仅可获得长达24个月，但当考虑所有失败时，估计继续MTX、GST或SSZ治疗60个月的患者的合并百分比分别为36、23和22%，当考虑仅因缺乏疗效而退出时，分别为75、73和53%，36和48%，仅考虑因毒性而退出。对所有退出进行的考克斯比例风险检验，在调整发表年份和研究类型后，显示患者继续使用MTX的时间显著长于其他三种药物;然而，当单独分析因无效而退出时，患者继续使用GST的时间显著长于MTX。观察性研究和随机对照试验的退出率无显著差异。RA患者使用MTX的时间明显长于其他缓解疾病的抗风湿药物。接受GST的患者中较高的退出率主要是由于高毒性，而SSZ和HCQ的大多数退出是由于缺乏疗效。观察性研究中的退出率与RCT中报告的退出率相似。
Objective. To summarize the evidence on treatment withdrawal rates reported in observational studies and randomized controlled trials (RCTs) of methotrexate (MTX), parenteral gold (GST), sulphasalazine (SSZ) and hydroxychloroquine (HCQ) among patients with rheumatoid arthritis (RA).Methods. Two independent Medline searches were used to retrieve relevant studies published between 1966 and 1997. Those which disclosed information on the number of patients withdrawing from the drug were retained. Cumulative probabilities of survival on treatment were then computed using actuarial survival estimates, and differences were tested using log-rank, Wilcoxon and Cox proportional hazards tests.Results. A total of 159 studies provided withdrawal information, and the numbers of patients who withdrew, in general or because of inefficacy or toxicity, could be abstracted from 110 studies contributing 142 treatment arms (MTX, 48; GST, 56; SSZ, 22; HCQ, 16). Data for HCQ were available only up to 24 months, but combined percentages of patients estimated to have continued MTX, GST or SSZ, respectively, for 60 months were 36, 23 and 22% when all failures were considered, 75, 73 and 53% when withdrawals due to lack of efficacy alone were considered, and 65, 36 and 48% when only withdrawals due to toxicity were taken into account. The Cox proportional hazards test performed on all withdrawals, after adjusting for year of publication and type of study, revealed that patients remained on MTX significantly longer than they did on the other three agents; however, the patients stayed significantly longer on GST than MTX when withdrawals for inefficacy were analysed separately. No significant differences in withdrawal rates were noted between observational studies and RCTs.Conclusion. Patients with RA stay significantly longer on MTX than on other disease-modifying anti-rheumatic drugs. Higher withdrawal rates among those given GST are mainly due to high toxicity, whereas the majority of withdrawals from SSZ and HCQ result from lack of efficacy. Withdrawal rates in observational studies are similar to those reported in RCTs.