The efficacy and safety of cyclosporine A plus androgen versus androgen alone for adult patients with non-severe aplastic anemia in China: a meta-analysis of randomized controlled trials

Whether combined CsA with androgen therapy was superior to androgen therapy alone in NSAA remains controversial. This study aimed to assess the efficacy and safety of combined therapy versus androgen therapy for NSAA patients using a meta-analytic approach. An electronic database of PubMed, EmBase, Cochrane library, CNKI, VIP, and Wanfang was systematically searched for randomized controlled trials (RCTs) from their inception to February 2020. The primary endpoint was effective rate, while the secondary endpoints included white blood cell (WBC), hemoglobin, platelet, and potential adverse events. The pooled results from included trials were calculated with the random-effects model. Forty-three RCTs recruited 2610 NSAA patients for the final quantitative meta-analysis. We noted that combined therapy was associated with an increased incidence of effective rate than androgen therapy alone (relative risk [RR]: 1.35; 95% confidence interval [CI]: 1.29–1.41; <i>P</i> &lt; 0.001). Moreover, patients treated with combined therapy were associated with higher WBC (weighted mean difference [WMD]: 1.22; 95%CI: 0.94–1.49; <i>P</i> &lt; 0.001), hemoglobin (WMD: 12.93; 95%CI: 8.86–17.01; <i>P</i> &lt; 0.001), and platelet (WMD: 8.65; 95%CI: 7.05–10.24; <i>P</i> &lt; 0.001). Finally, the pooled incidence of hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage were 0.35 (95%CI: 0.22–0.48), 0.24 (95%CI: 0.15–0.32), 0.22 (95%CI: 0.10–0.35), 0.19 (95%CI: 0.14–0.25), and 0.06 (95%CI: 0.01–0.11), respectively. This study found that combined CsA with androgen therapy was superior to androgen therapy alone for Chinese patients with NSAA, and the most common adverse of combined therapy included hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage.环孢素A（Cyclosporine A, CsA）联合雄激素疗法对比单纯雄激素疗法治疗非重型再生障碍性贫血（Non-Severe Aplastic Anemia, NSAA）的疗效优劣尚存争议。 本研究旨在采用Meta分析（meta-analysis）方法，评估NSAA患者接受联合疗法对比单纯雄激素疗法的疗效与安全性。 本研究系统检索了PubMed、Embase、Cochrane图书馆、中国知网（CNKI）、维普资讯（VIP）及万方数据知识服务平台自建库至2020年2月收录的随机对照试验（randomized controlled trial, RCT）文献。 本研究的主要结局指标为总有效率，次要结局指标包括白细胞（White Blood Cell, WBC）计数、血红蛋白（Hemoglobin, Hb）水平、血小板（Platelet, PLT）计数及潜在不良事件。 采用随机效应模型对纳入研究的合并效应量进行统计分析。 最终共纳入43项RCT，累计纳入2610例NSAA患者进行定量Meta分析。 研究结果显示，联合疗法组的总有效率显著高于单纯雄激素疗法组（相对危险度[Relative Risk, RR]：1.35；95%置信区间[Confidence Interval, CI]：1.29~1.41；P<0.001）。 此外，联合疗法组患者的WBC计数（加权均数差[Weighted Mean Difference, WMD]：1.22；95%CI：0.94~1.49；P<0.001）、Hb水平（WMD：12.93；95%CI：8.86~17.01；P<0.001）及PLT计数（WMD：8.65；95%CI：7.05~10.24；P<0.001）均显著高于单纯雄激素疗法组。 最终，多毛症、手颤、牙龈增生、肝功能损害及肾功能损害的合并发生率分别为0.35（95%CI：0.22~0.48）、0.24（95%CI：0.15~0.32）、0.22（95%CI：0.10~0.35）、0.19（95%CI：0.14~0.25）及0.06（95%CI：0.01~0.11）。 本研究结果表明，对于中国NSAA患者，CsA联合雄激素疗法的疗效显著优于单纯雄激素疗法；联合疗法最常见的不良事件包括多毛症、手颤、牙龈增生、肝功能损害及肾功能损害。