Objective: To investigate the association between positive anti-thyroid peroxidase antibody (TPOAb) and/or anti-thyroglobulin antibody (TgAb) and the occurrence of thyroid immune-related adverse events (irAEs) in patients with malignant tumors who treated with immune checkpoint inhibitors (ICIs). Methods: A case-control study. A total of 116 patients with malignant tumor who received ICIs treatment and underwent thyroid function evaluation at Peking Union Medical College Hospital from January 2017 to April 2023 were enrolled retrospectively, including 77 males and 39 females, with a median age of (M(Q1, Q3)) 63.0 (55.0, 70.0) years. The patients were divided into the euthyroid group (n=58) and the thyroid irAEs group (n=58) according to whether thyroid irAEs occurred after ICIs treatment. The clinical characteristics and baseline anti-thyroid antibodies associated with the occurrence of thyroid irAEs after ICIs treatment in patients with malignant tumors were evaluated. Variables with statistical significance in univariate analysis were included in multivariate logistic regression model to analyze the risk factors for thyroid irAEs in patients with malignant tumors who received ICIs treatment. Results: In irAEs group, therewore 4 (3.4%) cases of clinical thyrotoxicosis, 23(19.8%) cases of subclinical thyrotoxicosis, 23 (19.8%) cases of clinical hypothyroidism, and 8(6.9%) cases of subclinical hypothyroidism. The positive rate of anti-thyroid antibodies at baseline in the thyrioid irAEs group was higher than that in the euthyroid group［16/58（27.6%）vs 3/58（5.2%），P=0.001］. After at least one course of ICIs treatment, the incidence of thyroid irAEs in patients with positive anti-thyroid antibodies at baseline was 84.2% (16/19), whereas it was 43.3% (42/97) in patients with negative anti-thyroid antibodies(P=0.001). Univariate logistic regression analysis showed that gender (OR=2.812, 95%CI:1.257-6.293), baseline thyroid autoantibodies were positive (OR=6.984, 95%CI: 1.909-25.547), baseline TgAb positivity (OR=8.909, 95%CI: 1.923-41.280), and baseline TPOAb positivity (OR=7.304, 95%CI: 1.555-34.308) were associated with thyroid irAEs (all P<0.05). Multivariate logistic regression analysis indicated that baseline TgAb positivity (OR=7.637, 95%CI: 1.617-36.072) was a risk factor for thyroid irAEs (P=0.01). Conclusions: The incidence of thyroid irAEs is higher in patients who are positive for baseline TPOAb and/or TgAb compared to those who are negative for TPOAb and TgAb. Patients with positive TgAb at baseline are at high risk of developing thyroid irAEs.
目的： 探究抗甲状腺过氧化物酶抗体（TPOAb）和（或）抗甲状腺球蛋白抗体（TgAb）阳性与恶性肿瘤患者使用免疫检查点抑制剂（ICIs）后发生甲状腺免疫相关不良反应（irAEs）的关系。 方法： 病例对照研究。回顾性纳入2017年1月至2023年4月在北京协和医院接受ICIs治疗并行甲状腺功能评估的恶性肿瘤患者，共116例，男77例，女39例，年龄［M（Q1，Q3）］63.0（55.0，70.0）岁。根据ICIs治疗后是否发生甲状腺irAEs分为甲状腺功能正常组（n=58）和甲状腺irAEs组（n=58），评估临床特征及基线甲状腺自身抗体与恶性肿瘤患者ICIs治疗后发生甲状腺irAEs的关系。采用单因素分析筛选有统计学意义的变量纳入多因素logistic回归模型，分析接受ICIs治疗的恶性肿瘤患者发生甲状腺irAEs的危险因素。 结果： 甲状腺irAEs组中临床甲状腺毒症4例（3.4%）、亚临床甲状腺毒症23例（19.8%）、临床甲状腺功能减退症23例（19.8%）、亚临床甲状腺功能减退症8例（6.9%）。甲状腺irAEs组患者基线甲状腺自身抗体的阳性率高于甲状腺功能正常组，［16/58（27.6%）比3/58（5.2%），P=0.001］。接受至少1个疗程ICIs治疗后，基线甲状腺自身抗体阳性者甲状腺irAEs的发生率为84.2%（16/19），基线甲状腺自身抗体阴性者甲状腺irAEs的发生率为43.3%（42/97）（P=0.001）。单因素logistic回归分析结果显示，性别（OR=2.812，95%CI：1.257~6.293）、基线甲状腺自身抗体阳性（OR=6.984，95%CI：1.909~25.547）、基线TgAb阳性（OR=8.909，95%CI：1.923~41.280）、基线TPOAb阳性（OR=7.304，95%CI：1.555~34.308）是甲状腺irAEs发生的相关因素（均P<0.05）。多因素logistic回归分析结果显示，基线TgAb阳性（OR=7.637，95%CI：1.617~36.072）为甲状腺irAEs发生的危险因素（P=0.01）。 结论： 基线TPOAb和（或）TgAb阳性恶性肿瘤患者甲状腺irAEs的发生率高于TPOAb和TgAb阴性者，基线TgAb阳性者发生甲状腺irAEs的风险升高。.