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; P < 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; P < 0.001), hemoglobin (WMD: 12.93; 95%CI: 8.86–17.01; P < 0.001), and platelet (WMD: 8.65; 95%CI: 7.05–10.24; P < 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（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（NSAA）的疗效优劣，目前仍存在争议。本研究旨在通过Meta分析方法，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）、万方数据各电子数据库从建库至2020年2月的文献，以获取随机对照试验（RCTs）。本研究的主要终点为总体有效率，次要终点则包括白细胞（WBC）、血红蛋白、血小板水平及潜在不良事件。本研究采用随机效应模型对纳入研究的合并结果进行统计分析。
最终共有43项RCTs纳入本研究的定量Meta分析，累计纳入2610例NSAA患者。分析结果显示，联合疗法的总体有效率显著高于单纯雄激素疗法（相对危险度[RR]：1.35；95%置信区间[CI]：1.29~1.41；P < 0.001）。此外，接受联合疗法的患者其白细胞（加权均数差[WMD]：1.22；95%CI：0.94~1.49；P < 0.001）、血红蛋白（WMD：12.93；95%CI：8.86~17.01；P < 0.001）及血小板水平（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。最后，联合疗法相关不良事件的合并发生率分别为：多毛症0.35（95%CI：0.22~0.48）、手部震颤0.24（95%CI：0.15~0.32）、牙龈增生0.22（95%CI：0.10~0.35）、肝功能损害0.19（95%CI：0.14~0.25）及肾功能损害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反应包括多毛症、手部震颤、牙龈增生、肝功能损害及肾功能损害。