联合重组人血小板生成素方案治疗原发免疫性血小板减少症的近期疗效与安全性的Meta分析

Short-term efficacy and safety of rhTPO combined with traditional monotherapy regimen for the treatment of ITP：a Meta-analysis

目的 分析联用重组人血小板生成素（rhTPO）方案与传统单药方案治疗原发免疫性血小板减少症（ITP）的近期疗效与安全性.方法 采用计算机检索PubMed、万方数据库、维普数据库,中国知网（CNKI）,中国生物医学文献数据库（检索时间自建库至2017年9月）中,纳入rhTPO联合糖皮质激素或达那唑方案与传统单药方案治疗ITP的随机对照试验（RCT）.由2位经培训的研究人员按照关键词独立进行文献检索,剔除无法利用及质量不符合本研究纳入与排除标准文献.采用Jadad量表进行文献质量评分后,采用R软件对rhTPO方案联合传统糖皮质激素或达那唑治疗方案与传统单药方案治疗ITP疗效及不良反应情况,进行Meta分析.结果 通过文献检索并且追踪检索已获取全文的相关参考文献,共计10篇文献的10项RCT符合本研究纳入与排除标准,纳入研究的ITP患者为625例.其中,试验组患者为319例,对照组为306例.10篇文献的10项RCT的Jadad评分均较低,属于低质量RCT.本研究对10篇文献治疗ITP的近期疗效与不良反应的Meta分析结果如下.①近期显效率比较：7篇文献共计纳入420例ITP患者的7项RCT异质性检验结果示,各RCT间具有相对较高异质性（I2 =62.3％,P=0.01）.采用随机效应模型Meta分析结果显示,试验组和对照组近期显效率比较,差异无统计学意义（OR=2.95,95％CI：1.37～6.37,P=0.06）.去除大剂量地塞米松干扰因素后,5篇文献共计纳入287例ITP患者的5项RCT间具有轻度异质性（I2 =45％,P=0.12）.去除干扰因素后采用固定效应模型Meta分析结果显示,试验组显效率高于对照组,差异有统计学意义（OR=5.28,95％CI：2.95～9.44,P＜0.000 1）.②近期良效率比较：6篇文献纳入358例ITP患者的6项RCT间具有轻度异质性（I2 =38％,P=o.15）.采用固定效应模型Meta分析结果示,试验组与对照组良效率比较,差异无统计学意义（OR=1.30,95％CI：0.82～2.07,P=0.27）.③总有效率比较：9篇文献纳入563例ITP患者的RCT间异质性较低（I2=0％,P=0.65）.采用固定效应模型合并的Meta分析结果显示,试验组总有效率高于对照组,差异有统计学意义（OR=3.79,95％CI：2.50～5.73,P＜0.01）.④不良反应率比较：4篇文献的4项RCT中试验组与对照组不良反应率比较,差异无统计学意义（OR=3.56,95％CI：0.85～14.95,P=0.08）.结论 与传统糖皮质激素或达那唑单药方案比较,rhTPO联合糖皮质激素或达那唑治疗方案,能提高ITP患者的显效率和总有效率,但二者良效率及不良反应率比较,无显著差异.

Objective To evaluate the short-term efficacy and safety of recombinant human thrombopoietin （rhTPO） combined with glucocorticoid or danazol regimen and traditional monotherapy regimen in the treatment of idiopathic thrombocytopenic purpura （ITP）.Methods All the randomized controlled trial（RCT） about short-term efficacy and safety of combined rhTPO regimen with hormone or danazol regimen and traditional monotherapy regimen in the treatment of ITP were electronically collected by searching databases,including PubMed,Wanfang database,VIP database,China National Knowledge Infrastructure （CNKI）,China Biology Medicine disc（CBMdisc）.Retrieval time is up to September 2017.Independent search of the literature by two trained researchers,excluding articles that were not available and of non-compliant quality,and using the Jadad scale for literature quality scoring.Then,Meta-analysis of the efficacy and safety of rhTPO combined with traditional glucocorticoids or danazol and traditional monotherapy regimenin the treatment of ITP were preformed by using R software.Results A total of 10 RCTs involving 625 ITP patients were included by tracking the literatures and follow-up to relevant references with full text.Among them,there were 319 patients in the experimental group and 306 patients in the control group.Ten RCTs in 10 articles have lower Jadad scores which are low quality RCTs.The Metaanalysis of the short-term efficacy and adverse effects of 10 studies on ITP in the study were as follows.①Comparison of significant efficiency rate：7 RCTs of 420 ITP patients from 7 studies were found to have relatively high heterogeneity （I2=62.3%,P =0.01）.There was significant difference in significant efficiency rate between experimental group and the control group by the random effects model of Metaanalysis（OR=2.95,95% CI：1.37-6.37,P=0.06）.After removing factor of high-dose dexamethasone interference,5 RCTs involving 287 ITP patients had mild heterogeneity （I2 =45 %,P=0.12）,and Metaanalysis using a fixed-effect model showed that the significant efficiency rate of the experimental group was higher than that of the control group,and the difference was statistically significant （OR=5.28,95 % CI：2.95-9.44,P〈0.000 1）.②Comparison of good efficiency rate：Six RCTs involving 358 patients with ITP had mild heterogeneity （I2 =38 %,P=0.15）.Meta-analysis showed that there was no statistically significant difference in good efficiency rate between the experimental group and the control group by the fixed-effect model（OR =1.30,95 % CI：0.82-2.07,P =0.27）.③ Comparison of total effective rate：The heterogeneity between the 9 RCTs included in the 563 patients with ITP was low （I2=0%,P=0.65）.The Meta-analysis using the fixed-effect model showed that the total effective rate of the test group was higher than that of the control group （OR=3.79,95% CI：2.50-5.73,P〈0.01）.④Comparison of incidence of adverse reactions showed there was no significant difference in the incidence of adverse reactions between the experimental group and the control group （OR =3.56,95% CI：0.85-14.95,P =0.08） among 4 RCTs.Conclusions Compared with traditional monotherapy regimen,rhTPO combined with glucocorticoid or danazol regimen can improve significant efficiency rate and the total effective rate of ITP patients,but there were no significant differences in good efficiency rate and incidence of adverse reaction.