Mithoowani Siraj, Gregory-Miller Kathleen, Goy Jennifer, Miller Matthew C, Wang Grace, Noroozi Nastaran, Kelton John G, Arnold Donald M
Department of Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
McMaster Centre for Transfusion Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
Lancet Haematol. 2016 Oct;3(10):e489-e496. doi: 10.1016/S2352-3026(16)30109-0. Epub 2016 Sep 16.
Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response.
We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30 × 10/L) and complete (platelets >100 × 10/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model.
Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1·16, 95% CI 0·79-1·71; p=0·44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1·22, 95% CI 1·00-1·49; p=0·048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children.
In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High-dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count.
Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada.
高剂量地塞米松对既往未接受治疗的免疫性血小板减少症患者是否具有长期疗效及安全性尚不清楚。我们进行了一项系统评价和随机试验的荟萃分析，以确定高剂量地塞米松与泼尼松相比对长期血小板计数反应的影响。
我们检索了MEDLINE、Embase、护理学与健康相关文献累积索引以及Cochrane图书馆数据库，查找1970年至2016年7月发表的论文，以及2004年至2015年美国血液学会年会的摘要，以获取比较不同皮质类固醇方案用于既往未接受治疗且血小板计数有反应的免疫性血小板减少症患者的随机试验。仅比较皮质类固醇与其他干预措施的试验被排除。主要终点是高剂量地塞米松与标准剂量泼尼松相比在6个月时的总体（血小板>30×10⁹/L）和完全（血小板>100×10⁹/L）血小板计数反应。儿童和成人分别进行分析。效应估计值采用随机效应模型合并。
纳入了9项随机试验（n = 1138）。其中，5项试验（n = 533）比较了1至3个周期的地塞米松（每日40 mg，共4天）与泼尼松（1 mg/kg）治疗14 - 28天，随后在成人中逐渐减量。我们发现6个月时总体血小板计数反应无差异（合并比例54%对43%，相对风险[RR] 1.16，95%置信区间0.79 - 1.71；p = 0.44）。在14天时，地塞米松组的总体血小板计数反应更高（79%对59%，RR 1.22，95%置信区间1.00 - 1.49；p = 0.048）。地塞米松组报告的毒性较少。按治疗过程中累积皮质类固醇剂量分析数据时，长期反应率相似。在儿童中，不同高剂量皮质类固醇方案的初始血小板计数反应未观察到差异。
在既往未接受治疗的免疫性血小板减少症成人患者中，与标准剂量泼尼松相比，高剂量地塞米松并未改善持久的血小板计数反应。对于需要血小板计数快速上升的严重免疫性血小板减少症患者，高剂量地塞米松可能比泼尼松更受青睐。
加拿大卫生研究院、加拿大血液服务机构和加拿大卫生部。
