常用一线单药治疗儿童新诊断ITP Meta分析

Meta-analysis of first-line single-drug treatments in newly diagnosed immune thrombocytopenia in children

目的运用网状Meta分析方法评价儿童新诊断ITP不同一线方案治疗的早期及远期效果。方法计算机检索中、英文数据库,搜集不同一线方案改善ITP患儿血小板计数的随机对照试验(RCT),检索时间均为建库至2020年1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Stata 16.0软件进行网状Meta分析。结果共纳入9个RCT,包括716名患儿。网状Meta分析结果显示:对于初诊时血小板<20×10^(9)/L患儿,以诊断1周后血小板>20×10^(9)/L为评价标准,干预措施大剂量甲泼尼龙、小剂量泼尼松、anti-D、大剂量IVIg以及无药物干预之间相互比较,除大剂量IVIg优于anti-D(RR:1.14,95%CI:1.18-3.70,P=0.015)外,其他两两比较差异无显著性。以诊断4周后血小板>20×10^(9)/L为评价标准,大剂量IVIg、大剂量甲泼尼龙及无药物干预间相互比较差异无显著性。以诊断6个月后血小板>150×10^(9)/L为评价标准,干预措施小剂量IVIg、大剂量IVIg、大剂量甲泼尼龙、小剂量泼尼松、anti-D以及无药物干预之间相互比较,除小剂量泼尼松优于anti-D(RR:0.76,95%CI:0.60-0.97,P=0.03),大剂量IVIg有优于anti-D趋势(RR:1.28,95%CI:1.00-1.63,P=0.05)外,其他两两比较均未发现差异有显著性。以诊断12个月后血小板>100×10^(9)/L为评价标准,大剂量IVIg、大剂量甲泼尼龙及无药物干预间相互比较未见显著统计学差异。所有原始研究均未提及严重药物不良反应或严重出血导致的死亡。结论对于初诊时血小板<20×10^(9)/L的患儿,IVIg可以迅速提高血小板水平,不同剂量IVIg间差异无显著性。小剂量泼尼松有助于在诊断6个月后获得血小板完全反应,不同药物及无药物干预对诊断12个月后的远期预后无显著差异。

Objective To assess the early and long-term efficacy of different first-line interventions for newly diagnosed immune thrombocytopenia(ITP)in children by network meta-analysis.Methods Chinese and English databases were electronically searched to collect randomized controlled trials(RCTs)on first-line treatments efficacy in children′s newly diagnosed ITP from inception of database to January,2020.Two reviewers independently screened literature,extracted data and assessed risk of bias of included studies,then,network meta-analysis was performed by using the Stata 16.0 software.Results A total of 9 RCTs,involving 716 patients were included.For patients with platelet<20×10^(9)/L at the time of initial diagnosis,based on the efficacy evaluation of whether platelet>20×10^(9)/L after one week from diagnosis,interventions include high-dose methylprednisolone,low-dose prednisone,anti-D,high-dose IVIg,and no drug intervention,except the high-dose IVIg is better than anti-D(RR:1.14,95%CI:1.18-3.70,P=0.015),there was no significant difference between the other pairs.Based on the efficacy evaluation of whether platelet>20×10^(9)/L after 4 weeks from diagnosis,there was no significant statistical difference between high-dose IVIg,high-dose methylprednisolone,and no drug intervention.Based on the efficacy evaluation of whether platelet>150×10^(9)/L after 6 months from diagnosis,interventions were compared between low-dose IVIg,high-dose IVIg,high-dose methylprednisolone,low-dose prednisone,anti-D,and no drug intervention,except the low-dose prednisone was superior to anti-D(RR:0.76,95%CI:0.60-0.97,P=0.03)and high-dose IVIg was superior to anti-D(RR:1.28,95%CI:1.00-1.63,P=0.05),there was no significant difference between the other pairs(P>0.05).Based on the efficacy evaluation of whether platelet>100×10^(9)/L as the after 12 months from diagnosis,no significant statistical difference was found between low-dose IVIg,high-dose IVIg,low-dose prednisone,anti-D and no drug intervention.None of the original studies mentioned deaths caused by serious adverse drug reactions or severe bleeding.Conclusions For patients with platelet<20×10^(9)/L at the time of initial diagnosis,IVIg can rapidly increase platelet levels,there is no statistically significant difference between different doses of IVIg.Low-dose prednisone can help to obtain complete platelet response 6 months after diagnosis.There is no significant difference in the long-term prognosis with different drug interventions and without drug intervention.