小剂量环孢素联合左旋咪唑治疗非重型再生障碍性贫血疗效及安全性的meta分析

Efficacy and Safety of Low-dose Cyclosporine Combined with Levamisole in the Treatment of Non-severe Aplastic Anemia: A Meta-analysis

关键词:  环孢素  左旋咪唑  非重型再生障碍性贫血  meta分析

Key words:  cyclosporine  levamisole  non-severe aplastic anemia  meta-analysis

摘要:

目的 系统评价小剂量环孢素联合左旋咪唑治疗非重型再生障碍性贫血（non-severe aplastic anemia，NSAA）的疗效及安全性。方法 计算机检索The Cochrane Library、EMbase、PubMed、CBM、CNKI、维普及万方数据库，查找有关小剂量环孢素联合左旋咪唑治疗NSAA的随机对照试验，检索时间为建库至2019年7月。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用Rev Man 5.3进行meta分析。结果 共纳入12项研究，共1 071例患者。Meta分析结果显示，小剂量环孢素联合左旋咪唑与标准剂量环孢素治疗NSAA的总有效率差异无统计学意义[OR=1.23，95%CI（0.82，1.86），P=0.31]；但2种治疗方案的不良反应发生率具有统计学意义[OR=0.10，95%CI（0.07，0.16），P<0.000 01]；在血液学指标变化方面，2组治疗NSAA的血红蛋白变化[MD=1.83，95%CI（-1.55，5.20），P=0.29]、中性粒细胞变化[MD=-0.03，95%CI（-0.19，0.13），P=0.69]及网织红细胞变化[MD=-1.24，95%CI（-3.54，1.05），P=0.29]差异均无统计学意义，但2种治疗方案的血小板变化差异具有统计学意义[MD=18.23，95%CI（14.54，21.92），P<0.000 01]。结论 小剂量环孢素联合左旋咪唑与标准剂量环孢素比较，治疗NSAA的疗效相当，不良反应发生率更低，且更能升高血小板水平。但受纳入研究数量和质量的限制，该结论尚待更多高质量研究予以验证。

Abstract:

OBJECTIVE To systematically evaluate the efficacy and safety of low-dose cyclosporine combined with levamisole in the treatment of non-severe aplastic anemia(NSAA). METHODS The Cochrane Library, EMbase, PubMed, CBM, CNKI, VIP and Wanfang database were searched from inception to July 2019 to collect randomized controlled trials of low-dose cyclosporine combined with levamisole in the treatment of NSAA. Two reviewers independently screened studies, extracted date, and evaluated risk of bias of included studies. Meta-analysis was performed using RevMan 5.3 software. RESULTS Twelve literatures with a total of 1 071 patients were involved in this research. Meta-analysis showed that the total effective rate of low-dose cyclosporine combined with levamisole and standard dose cyclosporine in the treatment of NSAA was not statistically significant different[OR=1.23, 95% CI(0.82, 1.86), P=0.31]. However, there was statistically significance difference in the incidence of adverse reactions between the two therapeutic regiments[OR=0.10, 95% CI(0.07, 0.16), P<0.000 01]. And in terms of hematological indicators, the changes of hemoglobin[MD=1.83，95% CI(-1.55, 5.20), P=0.29], neutrophils[MD=-0.03, 95% CI(-0.19, 0.13), P=0.69] and reticulocytes[MD=-1.24, 95% CI(-3.54, 1.05), P=0.29] in the two groups were not statistically significant different, but there was statistically significant difference in the change of platelet between the two therapeutic regiments [MD=18.23, 95% CI (14.54, 21.92), P<0.000 01]. CONCLUSION The total effective rate of low dose cyclosporine combined with levamisole is comparable to standard dose cyclosporine in the treatment of NSAA. But the adverse reactions is lower and the platelet levels is higher in low dose cyclosporine combined with levamisole. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.