2665例多柔比星脂质体用药人群的严重超敏反应自动监测研究

Automatic monitoring research of doxorubicin liposomes-related severe hypersensitivity reactions in 2665 patients

目的:了解住院人群中多柔比星脂质体相关严重超敏反应的发生率、发生特征和风险因素,为临床用药提供参考。方法:依托“临床药物不良事件主动监测与智能评估警示系统-Ⅱ”(ADE-ASAS-Ⅱ),回顾性监测我院2012年1月1日-2019年12月31日期间,住院患者中所有使用多柔比星脂质体的用药人群,经系统自动筛选、智能报警,人工逐一甄别后,确定阳性病例,并进行深入分析。结果:使用多柔比星脂质体的用药人数共计2665例,10541例次,呈逐年递增趋势;共确定阳性病例31例,总发生率为1.16%;而同期4511例次多柔比星用药人群中为0例次。83.87%的严重超敏反应发生于第1周期;25.81%的阳性患者因超敏反应中断治疗;严重超敏反应累及系统例次最多的是呼吸系统(38.39%),主要表现为胸闷、喘憋,其次为皮肤系统(31.25%);治疗用药主要为地塞米松(46.94%)、异丙嗪(26.53%)。单因素Logistic回归结果显示,既往有药物过敏史、霍奇金淋巴瘤、非霍奇金淋巴瘤为影响因素,其中既往有药物过敏史为独立风险因素(AOR:4.899,95%CI:1.411~17.008)。结论:在给予预防用药的情况下,严重超敏反应发生率为1.16%;严重超敏反应可能与脂质体的关联性更强,大多发生于首次用药,有25.81%的阳性患者中断治疗,临床需警惕ADR的发生风险;既往有药物过敏史为独立风险因素,临床应重点关注。

Objective:To explore the incidence,characteristics and risk factors of doxorubicin liposomes-related severe hypersensitivity reactions in hospitalized patients,and provide references for clinical medication.Methods:Patients who used doxorubicin liposomes in our hospital from Jan 1st,2012 to Dec 31st,2019 were retrospectively monitored by active surveillance and assessment system-Ⅱof adverse drug events(ADE-ASAS-Ⅱ).And then data of the positive cases confirmed by the system automatic screening,intelligent alarm and manual screening one by one,were further analyzed.Results:The total number of doxorubicin liposomes used was 2665 cases,10541 times,which showing an increasing trend year by year.A total of 31 positive cases who were all given prophylactic medication were obtained in this study with a total incidence of 1.16%.However,in 4511 doxorubicin cases in the same period,there was no hypersensitivity reactions.83.87%of the positive cases developed severe hypersensitivity reactions during the first administration cycle.25.81%of the positive cases discontinued treatment due to the hypersensitivity reactions.The respiratory system(38.39%)was mostly involved in hypersensitivity reactions,which was mainly manifested as chest tightness and dyspnea.The second one was skin system(31.25%).The main therapeutic drugs were dexamethasone(46.94%)and promethazine(26.53%).Univariate Logistic regression results showed that a history of drug allergy,Hodgkin's lymphoma and non-Hodgkin's lymphoma were the influencing factors,among which a history of drug allergy was an independent risk factor(AOR:4.899,95%CI:1.411-17.008).Conclusion:The incidence of severe hypersensitivity reaction induced by doxorubicin liposomes was 1.16%based on prophylactic medication.Severe hypersensitivity reactions might be strongly related with liposomes,most of which occurred at the first time of administration.25.81%of the positive patients stopped treatment,and the history of drug allergy was the independent risk factor,which should be paid more attentions to,especially focus populations in clinic.