免疫检查点抑制剂甲状腺免疫相关不良反应分析

doi:10.19803/j.1672-8629.20210968

中国药物警戒 ›› 2023, Vol. 20 ›› Issue (1): 92-95.
DOI: 10.19803/j.1672-8629.20210968

免疫检查点抑制剂甲状腺免疫相关不良反应分析

郑轶¹, 翟映红^2∆, 郭晓晶¹, 许金芳¹, 迟立杰¹, 郭志坚¹, 陈晨鑫¹, 梁际洲¹, 韦连慧¹, 陈枭¹, 叶小飞^1#, 贺佳^1,*

¹海军军医大学卫勤系军队卫生统计学教研室,上海 200433;
²同济大学卫生统计学教研室,上海 200092

收稿日期:2021-11-04 发布日期:2023-01-19
通讯作者: ^*贺佳,女,教授·博导,药物流行病学及新药评价。E-mail: hejia63@yeah.net
^#为共同通信作者。
作者简介:郑轶,男,硕士,主治医师,药物流行病学。
^Δ为并列第一作者。
基金资助:
国家自然科学基金资助项目（82073671）; 上海市公共卫生体系建设三年行动计划学科带头人计划（GWV-10.2-XD22）; 上海市卫生和计划生育委员会优秀青年医学人才培养计划（2018YQ47）; 中国毒理学会临床毒理专项（CST2019CT201）; 中国毒理学会临床毒理专项（CST2019CT101）; 上海市公共卫生优青计划项目（GWV-10.2-YQ33）

Thyroid immune-related adverse reactions of immune checkpoint inhibitors

ZHENG Yi¹, ZHAI Yinghong^2∆, GUO Xiaojing¹, XU Jinfang¹, CHI Lijie¹, GUO Zhijian¹, CHEN Chenxin¹, LIANG Jizhou¹, WEI Lianhui¹, CHEN Xiao¹, YE Xiaofei^1#, HE Jia^1,*

¹Department of Military Medical Statistics, Naval Military Medical University, Shanghai 200433, China;
²Department of Health Statistics, Tongji University, Shanghai 200092, China

Received:2021-11-04 Published:2023-01-19

摘要/Abstract

摘要： 目的以免疫检查点抑制剂（ICIs）甲状腺免疫相关不良反应为例,初步探索基于中国药物警戒系统（CHPS）开展药品主动监测的可行性,为相关研究提供依据。方法基于2家哨点医院的CHPS数据,提取2020年1月1日至2021年6月30日应用过ICIs的肿瘤患者信息,以及未使用过ICIs的肿瘤患者信息作为对照。基于广义估计方程,对ICIs的甲状腺免疫相关不良反应进行探索。结果共纳入1 691名患者,其中ICIs组666名,对照组1 025名。应用广义估计方程模型处理患者的随访数据,充分考虑了多次重复测量数据间相关性的问题,发现显性甲状腺毒症有统计学意义（P<0.05）,发生率为4.50%,中位时间为41.5 d。结论 ICIs的应用可能会导致显性甲状腺毒症,临床医师在给患者应用ICIs时应注意显性甲状腺毒症的发生,确保患者用药安全。

关键词: 免疫检查点抑制剂, 甲状腺, 中国药物警戒系统, 主动监测, 药品不良反应

Abstract: Objective To explore the feasibility of active monitoring of drugs based on the Chinese Pharmacovigilance System (CHPS) in order to provide data for related research. Methods Based on the data from the CHPS of two sentinel hospitals, the information about tumor patients who had used ICIs and those who had not used ICIs between January 1, 2020 and June 30, 2021 was retrieved as controls. Based on the generalized estimation equation, the thyroid immune-related adverse reactions of ICIs were explored. Results A total of 1 691 patients were included, including 666 in the ICIs group and 1 025 in the control group. The generalized estimating equation model was used to process the follow-up data of patients while taking into consideration all the correlations between repeated measurement data. Tt was found that overt thyrotoxicosis was statistically significant (P<0.05). The incidence was 4.50%, and the median time to onset (TTO) was 41.5 days. Conclusion ICIs may cause overt thyrotoxicosis. When applying ICIs to patients, clinicians should be alert to the occurrence of overt thyrotoxicosis to ensure the safety of medications.

Key words: immune checkpoint inhibitors (ICIs), thyroid, Chinese Hospital Pharmacovigilance System (CHPS), active monitoring, adverse drug reactions

中图分类号:

郑轶, 翟映红, 郭晓晶, 许金芳, 迟立杰, 郭志坚, 陈晨鑫, 梁际洲, 韦连慧, 陈枭, 叶小飞, 贺佳. 免疫检查点抑制剂甲状腺免疫相关不良反应分析[J]. 中国药物警戒, 2023, 20(1): 92-95.

ZHENG Yi, ZHAI Yinghong, GUO Xiaojing, XU Jinfang, CHI Lijie, GUO Zhijian, CHEN Chenxin, LIANG Jizhou, WEI Lianhui, CHEN Xiao, YE Xiaofei, HE Jia. Thyroid immune-related adverse reactions of immune checkpoint inhibitors[J]. Chinese Journal of Pharmacovigilance, 2023, 20(1): 92-95.

参考文献

[1] ROUTY B, LE CHATELIER E, DEROSA L, et al.Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science (New York, NY), 2018, 359(6371): 91-97.
[2] PAN DW, WAN L.Preliminary monitoring of the safety of subcutaneous injection of domestic bortezomib with CHPS[J]. Chinese Journal of Pharmacovigilance, 2020, 17(12): 913-916.
[3] ZHANG YP, XIONG Y, JI HJ.Analysis of active monitoring of 486 cases of aescin sodium for injection[J]. Chinese Hospital Drug Evaluation and Analysis, 2019, 19(8): 985-986, 990.
[4] ZHAI Y, YE X, HU F, et al.Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system[J]. Journal for Immunotherapy of Cancer, 2019, 7(1): 286.
[5] XU CY, ZHONG MM, LI X.Research progress of immune checkpoint inhibitor-associated pneumonia[J]. Journal of Clinical Pulmonology, 2022 (2): 290-293.
[6] PENG Q, LI LF, ZHOU H, et al.Research progress of PD-1/PD-L1 inhibitor in advanced colorectal cancer[J]. Shandong Medicine, 2022, 62(1): 86-89.
[7] JIN G, YAO KY, SHEN XW, et al.A systematic review and meta-analysis of the efficacy of PD-1/PD-L1 immune checkpoint inhibitor and docetaxel in the treatment of non-small cell lung cancer[J]. Zhonghua Thoracic Surgery Electronic Journal, 2021, 8(4): 239-246.
[8] HU F, YE X, ZHAI Y, et al.Ear and labyrinth toxicities induced by immune checkpoint inhibitors: a disproportionality analysis from 2014 to 2019[J]. Immunotherapy, 2020, 12(7): 531-540.
[9] CHEN C, CHEN T, LIANG J, et al.Cardiotoxicity induced by immune checkpoint inhibitors: a pharmacovigilance study from 2014 to 2019 based on FAERS[J]. Frontiers in Pharmacology, 2021, 12: 616505.
[10] PAN X, SHI MH.Research status and multidisciplinary coping strategies of adverse reactions related to immune checkpoint inhibitors[J]. Chinese Journal of Medicine, 2021, 101(44): 3672-3676.
[11] LIU YY, JIANG PY, LI M, et al.Skin-related adverse reactions of immune checkpoint inhibitors[J]. China Journal of Leprosy and Dermatology, 2022, 38(2): 135-138.
[12] XU XZ, YANG J.Clinical diagnosis and treatment of skin adverse reactions caused by PD-1 inhibitors[J]. China Clinical Medicine, 2021, 28(6): 1079-1081.
[13] YE X, HU F, ZHAI Y, et al.Hematological toxicities in immune checkpoint inhibitors: a pharmacovigilance study from 2014 to 2019[J]. Hematological Oncology, 2020, 38(4): 565-575.
[14] MUIR CA, MENZIES AM, CLIFTON-BLIGH R, et al.Thyroid toxicity following immune checkpoint inhibitor treatment in advanced cancer[J]. Thyroid, 2020, 30(10): 1458-1469.
[15] HU MM, YANG Y, ZHAN TM, et al.Epidemiological characteristics analysis of 7843 cases of primary lung cancer[J]. Modern Oncology Med, 2021, 29(4): 682-685.
[16] XIA Y, PAN XP, LIU YY, et al.Application of generalized estimating equations in repeated measures data in clinical trials[J].Modern Preventive Medicine, 2005 (5): 444-445.
[17] ZHAO HY, ZENG XY, LIU FQ, et al.A systematic review of mediating time-dependent confounding and its control in pharmacoepidemiological studies[J]. Chinese Journal of Epidemiology, 2021, 42(12): 2179-2187.
[18] YUAN XD, XU YM, ZHOU J, et al.The effect of Chinese hospital pharmacovigilance system on the quality of adverse reaction reporting in two hospitals in a province[J]. Chinese Journal Pharmacovigilance, 2021, 18(2): 138-140.

免疫检查点抑制剂甲状腺免疫相关不良反应分析

Thyroid immune-related adverse reactions of immune checkpoint inhibitors

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