25例儿童患者应用免疫检查点抑制剂的不良反应调查和分析  

Investigation and Analysis of Adverse Drug Reactions Induced by Immune Checkpoint Inhibitors in 25 Children

作　　者：杜丰[1] 李哲[1] 郑英明 李新刚 DU Feng;LI Zhe;ZHENG Yingming;LI Xingang(Dept.of Pharmacy,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院西药剂科,北京100050

出　　处：《中国医院用药评价与分析》2023年第12期1521-1523,1527,共4页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：北京市自然科学基金资助项目(No.7192060)。

摘　　要：目的:调查和分析免疫检查点抑制剂在儿童患者应用中的不良反应。方法:回顾性调查2019年1月1日至2022年9月15日于该院接受程序性死亡受体1(PD-1)/程序性死亡受体配体1(PD-L1)抑制剂治疗各类恶性实体肿瘤和血液系统肿瘤的25例儿童患者(<18周岁)病历(共137次入院记录),记录患儿接受治疗期间发生的所有不良反应信息,并进行严重程度分级、相关性评价和影响因素分析。结果:25例使用PD-1/PD-L1抑制剂的患儿中,16例患儿合计发生20次不良反应。患儿发生的不良反应主要为发热(8例,发生率为32%)、氨基转移酶升高(3例,发生率为12%)和凝血功能障碍(2例,发生率为8%),此外还有白细胞计数降低、咳嗽、皮疹、腹泻、便潜血、乏力及食欲减退(各1例,发生率均为4%)等;其中,1—2级不良反应19次,3—5级不良反应共1次;相关性为“很可能”的不良反应共15次。4例患儿在发生不良反应后再次接受治疗,有2例出现了新的不良反应。经分析,并发症涉及3个及以上系统对不良反应的发生率有显著影响。结论:儿童患者使用PD-1/PD-L1抑制剂时,其不良反应发生情况与成人有所差异,较成人而言需要更多关注。临床需注意用药监护,提高儿童用药的安全性。OBJECTIVE:To investigate and analyze the adverse drug reactions induced by immune checkpoint inhibitors in children.METHODS:Retrospective investigation was performed on medical records of 25 children(<18 years old)who received programmed death-1(PD-1)/programmed death-ligand 1(PD-L1)inhibitors for treatment of various malignant solid tumors and hematologic tumors in the hospital from Jan.1st,2019 to Sept.15th,2022(totally 137 admissions records).All adverse drug reactions occurred during treatment were recorded,and severity classification,correlation evaluation and influencing factors analysis were performed.RESULTS:Of 25 children treated with PD-1/PD-L1 inhibitors,20 adverse drug reactions occurred in 16 patients.The main adverse drug reactions were fever(8 cases,32%),elevated aminotransferase(3 cases,12%)and coagulation dysfunction(2 cases,8%),in addition to decreased white blood cell count,cough,rash,diarrhea,fecal occult blood,fatigue and loss of appetite(1 case each,4%).There were 19 adverse drug reactions of grade 1 to 2 and 1 adverse drug reaction of grade 3 to 5,and the correlation was“highly likely”for a total of 15 times.Four patients were retreated after the occurrence of adverse drug reactions,and two patients developed new adverse drug reactions.After analysis,complications involving 3 or more systems had a significant impact on the incidence of adverse drug reactions.CONCLUSIONS:The occurrence of adverse drug reactions in children with PD-1/PD-L1 inhibitors differs from that of adults and requires more attention than in adults.Clinical attention should be paid to drug monitoring to improve the safety of drug use in children.

关 键 词：儿童 程序性死亡受体1/程序性死亡受体配体1抑制剂 免疫治疗 不良反应 相关性评价 

分 类 号：R969.3[医药卫生—药理学] R979.1[医药卫生—药学]