卡瑞利珠单抗相关甲状腺功能异常临床病例分析

Clinical case analysis of thyroid dysfunction induced by camrelizumab

目的探讨卡瑞利珠单抗相关甲状腺功能异常的发生情况和临床特征。方法研究对象选自2020年6月至2021年9月在长治医学院附属和平医院住院接受卡瑞利珠单抗治疗的恶性肿瘤患者。收集符合纳入标准患者的电子病历,记录其一般情况、卡瑞利珠单抗用药情况、联合用药情况和应用卡瑞利珠单抗前后甲状腺功能(甲功)检查结果;对发生甲功异常的患者,应用Naranjo不良反应因果关系评估量表进行药物与损伤的因果关系评价,根据评价结果为"肯定"和"很可能"者的病历资料进行甲功异常的临床特征分析。结果纳入分析的患者共71例,22例(31.0%)发生卡瑞利珠单抗相关甲功异常(因果关系评估结果均为"很可能"),首次发现甲功异常时诊断为甲功减退(甲减)和甲功亢进(甲亢)者各11例,甲亢患者中有3例后期演变为甲减,甲减和甲亢发生率分别为19.7%和11.3%。22例患者中,男性15例,女性7例;年龄47~78岁;肺癌10例,胃癌4例,食管癌3例,肝癌和乳腺癌各2例,腹膜大网膜间皮瘤1例;卡瑞利珠单抗单药治疗者3例,联合化疗和/或靶向药物治疗者19例;甲功异常发生在卡瑞利珠单抗治疗的第1~6个周期,15例(68.2%)发生在第1~3个周期。最初诊断甲减的11例患者中6例无明显症状,5例有乏力症状(1例合并淡漠),4例为亚临床甲减;严重程度4例为1级,7例为2级。最初诊断甲亢的11例患者均无明显症状,其中5例为亚临床甲亢;严重程度均为1级;有3例患者在继续卡瑞利珠单抗治疗3、6和7个周期后演变为甲减,严重程度均为2级。22例患者均未停用卡瑞利珠单抗。1级甲减和甲亢患者未给予干预,3例甲亢患者甲功自行恢复正常,其余患者甲功无明显变化;10例2级甲减患者接受了甲状腺激素替代治疗,2例甲功恢复正常,5例好转,3例无明显变化。结论甲功异常是卡瑞利珠单抗十分常见的不良反应,既可表现为甲减,也可表现为甲亢,并可由甲亢演变为甲减,严重程度多为1~2级,一般不需要停药。对发生2级甲减患者应给予甲状腺激素替代治疗。

Objective To explore the occurrence and clinical characteristics of thyroid dysfunc⁃tion caused by camrelizumab.Methods The subjects were selected from all malignant tumor patients who were treated with camrelizumab during hospitalization in Heping Hospital Affiliated to Changzhi Medical College from June 2020 to September 2021.The electronic medical records of patients who met the inclusion criteria were collected,and the general conditions,camrelizumab application,combined medication,and the thyroid function test results before and after the application of camrelizumab were collected.The causality between drugs and injuries in patients who developed thyroid dysfunction was assessed using Naranjo′s causality assessment scale.The clinical characteristics of thyroid dysfunction were analyzed based on the medical records that had evaluation results of"certainly"or"probably".Results A total of 71 patients were included in the analysis,and 22 patients(31.0%)developed camrelizumab⁃related thyroid dysfunction(causality assessment results were all"probably").When thyroid dysfunction was found for the first time,hypothyroidism and hyperthyroidism were diagnosed in 11 patients,respectively,and 3 patients with hyper⁃thyroidism developed into hypothyroidism later.The incidences of hypothyroidism and hyperthyroidism were 19.7%and 11.3%respectively.Among the 22 patients,15 were male and 7 were female,aged 47⁃78 years;10 patients were with lung cancer,4 with gastric cancer,3 with esophageal cancer,2 with liver cancer,2 with breast cancer,and 1 with peritoneal omental mesothelioma;3 patients were treated with camrelizumab monotherapy,and 19 were treated with camrelizumab combined with chemotherapy and/or targeted drug therapy.Thyroid dysfunction all occurred in the first to sixth cycles of camrelizumab treatment,of which 15(68.2%)in the first to third cycles.Of the 11 patients with initial diagnose of hypothyroidism,6 had no obvious symptoms,5 had fatigue(1 was complicated with apathy),and 4 were subclinical hypothyroidism;the severity was grade 1 in 4 cases and grade 2 in 7 cases.None of the 11 patients with initial diagnose of hyperthyroidism had significant symptoms,and 5 of them had subclinical hyperthyroid.All of the 11 cases were grade 1 in severity,3 developed into hypothyroidism after 3,6,and 7 cycles of camrelizumab treatment,which was grade 2 in severity.None of the 22 patients discontinued camrelizumab.No intervention was given to the patients with grade 1 hypothyroidism and hyperthyroidism,of which 3 patients with hyperthyroidism returned to normal on their own and the remaining showed no obvious changes in their thyroid function.Ten patients with grade 2 hypothyroidism received thyroid hormone replacement therapy;thyroid function was normal in 2 patients,improved in 5 patients,and without obvious changes in 3 patients.Conclusions Thyroid dysfunction is a very common adverse reaction of camrelizumab,which can present as both hypothy⁃roidism and hyperthyroidism,and initial hyperthyroidism can evolve to hypothyroidism.Thyroid dysfunction was mostly grade 1⁃2 in severity and the drug does not need to be discontinued generally.Patients with grade 2 hypothyroidism should be given thyroid hormone replacement therapy.