依达赛珠单抗在中国人群对达比加群酯抗凝作用的逆转效应

Reversal effect of idarucizumab on the anticoagulant effect of dabigatran etexilate in Chinese population

目的评价依达赛珠单抗在中国人群对达比加群酯抗凝作用的逆转效应。方法本文为开放标签多中心研究。收集2018年10月至2020年7月全国11个中心因无法控制出血、需紧急手术或其他有创操作需要使用依达赛珠单抗逆转达比加群酯抗凝作用的患者。分为两组:大出血组(A组)为发生无法控制、危及生命的出血者;非大出血组(B组)为需要急诊外科手术或其他有创操作者。两组患者均接受静脉输注依达赛珠单抗5 g。主要终点为患者首次输注依达赛珠单抗结束至最后1次输注完成后4 h内稀释凝血酶时间和蝰蛇毒凝血时间最大逆转效应。同时记录首次输注至第2次输注完成后5 d内不良事件的发生情况。结果研究纳入19例患者,其中男10例,女9例,年龄(71.4±13.0)岁,年龄范围48~93岁。A组13例,B组6例。4 h内达比加群酯抗凝效应最大逆转的中位值均为100%。治疗期内,17例(89.5%,17/19)患者出现不良事件。其中重点报道不良事件9例,包括2例(10.5%,2/19)血栓栓塞事件、4例(21.1%,4/19)严重不良事件,经研究者判断,严重不良事件及血栓栓塞事件均与依达赛珠单抗无关;3例(15.8%,3/19)出现研究者定义的药物相关的不良事件。治疗期内患者无死亡。研究中抗依达赛珠抗体结果均为阴性,并与免疫原性无关。结论给予依达赛珠单抗5 g后最初4 h内达比加群酯抗凝作用的中位最大逆转效应达100%,且安全性好对临床实践有借鉴价值。

Objective To evaluate the reversal of the anticoagulation effect of dabigatran with idarucizumab in Chinese patients.Methods From October 2018 to July 2020,19 patients in 11 centers across the country who needed to use idarucizumab to reverse the anticoagulation effect of dabigatran etexilate due to uncontrolled bleeding,emergency surgery or other invasive procedures were enrolled.The patients who treated with dabigatran etexilatewere included due to that they had uncontrolled/life-threatening bleeding requiring urgent medical or surgical intervention(group A);or patients who might not have been bleeding,but required an emergency surgery or other invasive procedure for a condition other than bleeding(group B).Both groups received an intravenous infusion of 5 g idarucizumab.The primary endpoint was the maximum reversal of the anticoagulation effect of dabigatran based on the diluted thrombin time(dTT)and ecarin clotting time(ECT)evaluated at the central laboratory,from the end of the first infusion up to 4 hours after the last infusion.Safety during the treatment period was assessed between the first infusion and 5 days after the last infusion.Meanwhile,the adverse events occurred from the first infusion to the 5 days afterthe second infusion were recorded.Results Eleven sites recruited a total of 19 patients(group A:13 patients;group B:6 patients).There were 10 males and 9 females,aged(71.4±13.0)years old,ranging from 48 to 93 years old.The median maximum reversal of the anticoagulation effect of dabigatran from the end of the first infusion up to 4 hours after the last infusion was both 100%.During the treatment period,any adverse events(AE)occurred in 17 patients(89.5%,17/19).Key AE include 2 patients reported thrombotic events(10.5%,2/19),and serious AE occurred in 4 patients(21.1%,4/19);these events were considered not related to idarucizumab by the investigators.Investigator defined drug-related AE occurred in 3 patients(15.8%,3/19).No death was reported during the treatment period.Anti-drug antibody results were all negative,and no immunogenicity was identified.Conclusion The median maximum reversal of the anticoagulation effect of dabigatranwas achieved at 100%within the first 4 hours after treatment of 5 g idarucizumab,with a favorable safety profile.The study demonstrates idarucizumab as a promising treatment for Chinese patients who require reversal of dabigatran under these circumstances.