Graves病的131I治疗和抗甲状腺药物治疗：随机对照试验荟萃分析

131I therapy versus antithyroid drugs in Graves＇disease：a meta-analysis of randomized controlled trials

目的 通过荟萃分析比较131I治疗与抗甲状腺药物治疗对Graves病的临床治疗效果,包括眼病的发生或恶化、甲状腺功能亢进症（甲亢）的治愈率、甲状腺功能减退症（甲减）发生率、复发率和不良反应.方法 以＂Graves病＂、＂放射性碘＂、＂抗甲状腺药物＂、＂治疗＂等为关键词检索了1990年至2016年在PubMed检索系统、荷兰医学文摘数据库、科学网、中国生物医学文献服务系统（SinoMed）和中国国家知识基础设施（中国知网）等数据库中发表的关于Graves病131I和抗甲状腺药物治疗效果的随机对照试验（RCTs）研究文献,比较131I治疗与抗甲状腺药物治疗对Graves病患者的疗效.采用12.0版Stata软件进行荟萃分析.结果以置信区间95%CIs风险比表示.利用固定效应模型和随机效应模型,根据研究的异质性,进行综合分析.结果 最终纳入了1992年至2015年的17项RCTs,共4024例患者.综合分析结果表明：131I治疗组和抗甲状腺药物治疗组患新眼病率分别为23.3%和16.1%,甲亢的治愈率分别是77.8%和45.6%,甲减发病率分别是19.7%和9.3%,甲亢复发率分别是6.3%和35.0%.131I治疗会增加患者患眼病（RR=1.36,95%CI：[1.04,1.77];P=0.024）、眼病恶化（RR=1.76,95%CI：[1.30,2.38];P〈0.001）和甲减的风险（RR=1.99,95%CI：[1.34,2.98];P=0.001）.但是,与抗甲状腺药物治疗相比,131I治疗的甲亢治愈率高（RR=1.66,95%CI：[1.49,1.86];P〈0.001）、复发率低（RR=0.16,95%CI：[0.08,0.33];P〈0.001）,且不良反应的发生率相对较低（RR=0.22,95%CI：[0.10,0.49];P〈0.001）.结论 与抗甲状腺药物治疗相比,131I治疗的甲亢治愈率相对较高,复发率相对较低.但是,131I治疗同时也会增加患眼病和甲减的风险.因此,要采取更积极的干预措施,以减少和预防这些合并症的发生.

Objective To compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes using meta-analysis, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate, and adverse events. Methods Randomized controlled trials（RCTs） published in PubMed, Embase, Web of Science, SinoMed, and National Knowledge Infrastructure, China were analyzed. These studies were published between 1990 and 2016. The selected key search terms were as follows： Graves＇ disease, radioiodine, and antithyroid drugs. Therapy was systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs among patients with Graves＇ disease. STATA software v.12.0 was used for data analysis. Results were expressed as risk ratio with 95% confidence intervals（CIs）. Pooled estimates were determined using fixed-effect model or random-effect model, depending on the heterogeneity among studies. Results A total of 17 RCTs involving 4024 patients satisfied the inclusion criteria; these studies were published between 1992 and 2015. Comprehensive analysis and results indicated that the rate of new ophthalmopathy developed in radioiodine therapy group and antithyroid drug group was 23.3% and 16.1%, respectively. Correspondingly, the hyperthyroid cure rate was 77.8% and 45.6%, the hypothyroidism rate was 19.7% and 9.3%, and the hyperthyroid relapse rate was 6.3% and 35.0%, respectively. Results also showed that radioiodine treatment increased the risk of new ophthalmopathy（RR=1.3, 95% CI：[1.04, 1.77];P=0.024）, development or worsening of ophthalmopathy（RR=1.76, 95% CI： [1.30, 2.38]; P〈0.001）, and hypothyroidism（RR=1.76, 95% CI： [1.30, 2.38]; P〈0.001）. Furthermore, radioiodine treatment presented a higher hyperthyroid cure rate（RR=1.66, 95% CI： [1.49, 1.86];P〈0.001）, lower recurrence rate（RR=0.16, 95% CI： [0.08, 0.33];P〈0.001）, and lower incidence of adverse events（RR=0.22, 95% CI： [0.10, 0.49];P〈0.001） than those of antithyroid drugs. Conclusions Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate than those of antithyroid drugs. However, this treatment also increases the risk of ophthalmopathy and hypothyroidism. Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we recommend radioiodine therapy as treatment option for patients with Graves＇ disease.