沙利度胺治疗强直性脊柱炎有效性与安全性的系统评价

Effectiveness and Safety of Thalidomide for Ankylosing Spondylitis: A Systematic Review

目的 系统评价沙利度胺治疗强直性脊柱炎的有效性和安全性。方法 计算机检索Ovid MEDLINE（1946～2014.2.1）、EMbase（1947～2014.2.1）、CENTRAL（2014年第1期）、CBM（1978～2014.2.1）、CNKI（1994～2014.2.1）、Wan Fang Data（1980～2014.2.1）和VIP（1989～2014.2.1）数据库,查找所有沙利度胺治疗强直性脊柱炎的随机对照试验（RCT）。由2位评价员按照纳入与排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用Rev Man 5.2软件进行Meta分析。结果 共纳入7个RCT,包括544例患者。Meta分析结果显示：与空白对照相比,沙利度胺能提高临床缓解;但在Bath强直性脊柱炎活动指数（BASDAI）、Bath强直性脊柱炎功能指数（BASFI）和次要结局指标方面,沙利度胺无明显优势,且其总退出/失访率增加。与SSZ相比,沙利度胺用于达到ASAS20缓解后维持治疗时能提高维持缓解率;其余指标方面,二者相仿。与NSAIDs相比,沙利度胺用于达到ASAS20缓解后维持治疗时能提高维持缓解率,提高活动性强直性脊柱炎临床缓解;在次要结局指标方面,二者相似;其不良反应发生率和总退出/失访率较高。结论 沙利度胺与空白组相比,能提高临床缓解,但退出/失访率也明显增高。沙利度胺与SSZ相比,能提高获得ASAS20缓解的维持缓解率。沙利度胺用于达到ASAS20缓解的维持治疗时,优于NSAIDs,且能提高临床缓解;但其不良反应发生率和总退出/失访率较高。受纳入研究数量和质量限制,上述结论尚待开展更多高质量研究加以证实。

Objective To systematically review the effectiveness and safety of thalidomide for ankylosing spondylitis （AS）. Methods Databases including Ovid MEDLINE （1946 to 2014.2.1）, EMbase （1947 to 2014.2.1）, CENTRAL （Issue 1, 2014）, CBM （1978 to 2014.2.1）, CNKI （1994 to 2014.2.1）, WanFang Data （1980 to 2014.2.1） and VIP （1989 to 2014.2.1） were searched for randomized controlled trials about the effectiveness and safety of thalidomide for AS. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Meta-analysis was then conducted using RevMan 5.2 software. Results Seven RCTs were included involving 544 patients. The results of meta-analysis showed that, compared with the blank group, thalidomide increased clinical remission, but it showed no obvious advantage in Bath Ankylosing Spondylitis Disease Activity Index （BASDAI）, Bath Ankylosing Spondylitis Functional Index （BASFI）, and secondary outcome index, with an increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; and for other outcomes it was similar to SSZ. Compared with NSAIDs, thalidomide increased the rate of maintaining remission when it was used in the maintenance treatment after the patients attained ASAS20; it increased clinical remission; for secondary outcomes it was similar to NSAIDs; and it had a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop- out. Conclusion Compared with the blank group, thalidomide increases clinical remission, with an obviously-increased total rate of withdrawal/drop-out. Compared with SSZ, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20. Compared with NSAIDs, thalidomide increases the rate of maintaining remission when it is used in the maintenance treatment after patients attain ASAS20; it also increases clinical remission; but it has a higher incidence of adverse reaction as well as an increased total rate of withdrawal/drop- out. Due to limited quantity and quality of the included studies, the above conclusion needs to be verified by conducting more high quality studies.