PD-1抑制剂相关甲状腺不良反应的临床研究  

Clinical study of adverse thyroid reactions associated with PD-1 inhibitor

作　　者：岳艳 江彤[2] 冯潇宇 郭兵 YUE Yan;JIANG Tong;FENG Xiao-yu;GUO Bing(Graduate School of Qinghai University,Xining 810000,Qinghai,China;Department of Endocrinology,Affili-ated Hospital of Qinghai University,Xining 810000,Qinghai,China;Department of Endocrinology,Bazhong Central Hospital,Bazhong 636000,Sichuan,China;Department of Hepatobiliary,Pancreatic,Splenic and Vascu-lar Surgery,Bazhong Central Hospital,Bazhong 636000,Sichuan,China)

机构地区：[1]青海大学研究生院,西宁810000 [2]青海大学附属医院内分泌科,西宁810000 [3]巴中市中心医院内分泌科,巴中636000 [4]巴中市中心医院肝胆胰脾,巴中636000

出　　处：《医学研究生学报》2022年第12期1309-1313,共5页Journal of Medical Postgraduates

摘　　要：目的 PD-1抑制剂相关甲状腺不良反应的发生率较高,文中旨在探讨恶性肿瘤患者经PD-1抑制剂治疗后甲状腺不良反应的发生情况、临床特征及影响因素。方法 回顾性收集2019年5月至2021年1月青海大学附属医院、青海省人民医院、青海省肿瘤医院经病理组织学确诊为恶性肿瘤并接受PD-1抑制剂治疗的恶性肿瘤患者的临床数据。以2~3周为1个周期监测甲状腺功能,观察患者有无甲状腺功能异常的临床表现,分析PD-1抑制剂治疗后甲状腺不良反应的发生概率、发生时间、临床类型、分级分型及影响因素。结果 122例恶性肿瘤患者经PD-1抑制剂治疗后甲状腺功能异常的发生率为43.4%(53/122)。新发甲状腺功能异常的发生率为29.6%(29/98),其中亚临床甲减20例(20.4%)、甲减5例(5.1%)、甲亢4例(4.1%)。PD-1抑制剂首次给药至发生甲状腺功能异常的中位时间为63(14~252)d。Logistic回归分析显示,女性肿瘤患者相比于男性肿瘤患者经PD-1抑制剂治疗后其发生甲状腺疾病的风险增加3.772倍(0R=3.772,95%CI:1.597~8.908),基线TPOAb阳性的肿瘤患者经PD-1抑制剂治疗后相比于基线TPOAb阴性的肿瘤患者其发生甲状腺疾病的风险增加12.877倍(0R=12.877,95%CI:1.539~107.720)。PD-1抑制剂治疗后I级甲状腺irAEs的发生率为27.0%(33/122),II级甲状腺irAEs的发生率为16.4%(20/122),无III-IV级甲状腺irAEs。新发22例I级甲状腺irAEs(22.4%),7例II级甲状腺irAEs(7.1%)。结论 甲减是PD-1抑制剂常见不良反应,女性,TPO-Ab阳性的患者为发展为甲状腺功能异常的危险因素,前3个月的发生率较高,但严重程度较轻,治疗过程中无需中断治疗。Objective The incidence of adverse thyroid reactions associated with PD-1 inhibitors is relatively high. In this study, the incidence, clinical characteristics and influencing factors of adverse thyroid reactions in patients with malignant tumor treated with PD-1 inhibitor were further discussed. Methods Clinical data of patients with malignant tumors diagnosed by histopathology and treated with PD-1 inhibitor, in the Affiliated Hospital of Qinghai University, Qinghai Provincial People’s Hospital, and Qinghai Provincial Cancer Hospital, from May 2019 to January 2021, were collected retrospectively. The thyroid function was monitored in a circle of 2 to 3 weeks to observe whether the patients had clinical manifestations of thyroid dysfunction. Incidence, occurrence time, clinical type, grading and influencing factors of thyroid adverse reactions after PD-1 inhibitor treatment were analyzed. Results The incidence of thyroid dysfunction in 122 malignant tumor patients treated with PD-1 inhibitor was 43.4%(53/122 cases).The incidence of new thyroid dysfunction was 29.6%(29/98 cases), including 20 cases of subclinical hypothyroidism(20.4%), 5 cases of hypothyroidism(5.1%), and 4 cases of hyperthyroidism(4.1%).The median time from the first administration of PD-1 inhibitor to the onset of thyroid dysfunction was 63 days, with the earliest being 14 days and the latest 252 days. Logistic regression analysis showed that, the risk of thyroid disease among female tumor patients was increased by 3.772 times after PD-1 inhibitor treatment than that among male patients(OR=3.772,95%CI:1.597~8.908). Compared with patients with baseline TPO Ab-negative tumors, the risk of thyroid disease in patients with baseline TPO Ab-positive tumors was increased by 12.877 times after treatment with PD-1 inhibitor(OR=12.877,95%CI:1.539~107.720). After PD-1 inhibitor treatment, the incidence of grade I thyroid IRAs was 27.0%(33/122), and that of grade II thyroid IRAs was 16.4%(20/122), and no grade III-IV thyroid IRAs was reported. 22 new cas

关 键 词：PD-1抑制剂 免疫相关不良反应 甲状腺功能异常 

分 类 号：R581[医药卫生—内分泌]