接受新一代BCR-ABL酪氨酸激酶抑制剂治疗的慢性髓性白血病患者发生动脉和静脉闭塞事件的风险：一项系统评价和荟萃分析。

Risk of arterial and venous occlusive events in chronic myeloid leukemia patients treated with new generation BCR-ABL tyrosine kinase inhibitors: a systematic review and meta-analysis.

作者信息

Haguet Hélène, Douxfils Jonathan, Mullier François, Chatelain Christian, Graux Carlos, Dogné Jean-Michel

机构信息

a Department of Pharmacy , University of Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Namur , Belgium.

b Haematology Laboratory , Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) , Yvoir , Belgium.

出版信息

Expert Opin Drug Saf. 2017 Jan;16(1):5-12. doi: 10.1080/14740338.2017.1261824. Epub 2016 Nov 28.

DOI:10.1080/14740338.2017.1261824

PMID:27852118

Abstract

BACKGROUND

A previous meta-analysis demonstrated that 3 of the new-generation BCR-ABL tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib and ponatinib) are associated with an increased risk of vascular occlusive events in patients with Ph+ chronic myeloid leukemia compared with imatinib. This meta-analysis of randomized controlled trials aims at assessing these risks separately.

METHODS

The literature search was performed by two independent reviewers following the previous protocol (PROSPERO 2014:CRD42014014147). A random-effects model and a fixed-effect model were used according to the characteristics of the included studies. Peto odds ratios with 95%CI were computed.

RESULTS

Overall, 4.78% of patients developed arterial occlusive events with new generation TKIs compared with 0.96% with imatinib. Ponatinib (OR:3.26; 95%CI:1.12 to 9.50), nilotinib (OR: 3.69; 95%CI:2.29 to 5.95) and dasatinib (OR:3.32; 95%CI:1.37 to 8.01) are all associated with a higher risk of arterial occlusive events than imatinib. Venous occlusive events occur in 0.72% of patients treated with new generation TKIs and in 0.27% of imatinib-treated patients. Overall, a trend toward an increase of the rate of venous occlusive events with new-generation TKIs (OR:2.17; 95%CI:0.90 to 5.25) was highlighted but stratifications by treatment gave nonsignificant results.

CONCLUSIONS

Vascular occlusive events associated with new-generation BCR-ABL TKIs are driven by arterial occlusive events.

摘要

背景

先前的一项荟萃分析表明，与伊马替尼相比，新一代BCR-ABL酪氨酸激酶抑制剂（TKIs）（达沙替尼、尼洛替尼和波纳替尼）中的3种与Ph+慢性髓性白血病患者血管闭塞事件风险增加相关。这项随机对照试验的荟萃分析旨在分别评估这些风险。

方法

由两名独立的审阅者按照先前的方案（PROSPERO 2014:CRD42014014147）进行文献检索。根据纳入研究的特征使用随机效应模型和固定效应模型。计算了具有95%置信区间的Peto比值比。

结果

总体而言，新一代TKIs治疗的患者中有4.78%发生动脉闭塞事件，而伊马替尼治疗的患者中这一比例为0.96%。波纳替尼（OR:3.26；95%CI:1.12至9.50）、尼洛替尼（OR:3.69；95%CI:2.29至5.95）和达沙替尼（OR:3.32；95%CI:1.37至8.01）与动脉闭塞事件风险高于伊马替尼均相关。静脉闭塞事件发生在新一代TKIs治疗患者中的比例为0.72%，伊马替尼治疗患者中的比例为0.27%。总体而言，突出显示了新一代TKIs治疗静脉闭塞事件发生率增加的趋势（OR:2.17；95%CI:0.90至5.25），但按治疗分层的结果无统计学意义。