Immune checkpoint inhibitor-associated thyroid dysfunction: a disproportionality analysis using the WHO Adverse Drug Reaction Database, VigiBase

• Published in: European journal of endocrinology Vol. 182; no. 1; pp. 1 - 9
• Main Authors: Bai, Xuefeng, Chen, Xiaoyu, Wu, Xiaohong, Huang, Yinqiong, Zhuang, Yong, Lin, Xiahong
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.01.2020; Oxford University Press
• Subjects: Adolescent; Adult; Aged; Child; Child, Preschool; Clinical Study; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hyperthyroidism; Hyperthyroidism - immunology; Hyperthyroidism - pathology; Hypothyroidism; Hypothyroidism - immunology; Hypothyroidism - pathology; Immune checkpoint inhibitors; Immunosuppressive agents; Infant; Infant, Newborn; Male; Melanoma; Middle Aged; Odds Ratio; Patients; Thyroid; Thyroid diseases; Thyroid Diseases - immunology; Thyroid Diseases - pathology; Thyroid gland; Thyroid Gland - immunology; Thyroid Gland - pathology; Thyroiditis; Young Adult
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-19-0535

Objective Our study aimed to identify and characterize thyroid dysfunctions associated with immune checkpoint inhibitors (ICIs). Design Data were obtained from VigiBase, between January 1, 2011 to March 6, 2019. Methods All thyroid drug-adverse events are classified by group queries according to the Medical Dictionary for Regulatory Activities. Information component (IC) and reporting odds ratio (ROR) were considered as measures of disproportionality for the assessment of association between ICIs and thyroid dysfunctions. We used IC to identify meaningful drug-adverse events while using ROR to compare differences in the reporting of drug-adverse events caused by different ICI subgroups. Positive IC values are deemed significant. Results Compared with the full database, the following ICI-associated thyroid dysfunctions were over-reported: hypothyroidism (1125 reports for ICIs vs 12495 for all drugs; Information Component 4.28 (95% CI: 4.18–4.35)), hyperthyroidism (926 vs 7538; 4.66 (95% CI: 4.55–4.74)), thyroiditis (294 vs 1237; 5.40 (95% CI: 5.21–5.54)), thyrotoxic crisis (11 vs 288; 3.55 (95% CI: 2.61–4.20)). Hypothyroidism was over-reported for patients treated with ICI combination therapy versus those treated with ICI monotherapy (ROR 1.3 (95% CI: 1.1–1.7)), and the same was observed for hyperthyroidism (ROR: 1.9 (95% CI: 1.5–2.4)), thyroiditis (ROR: 3.3 (95% CI: 2.3–4.8)), thyrotoxic crisis (ROR: 11.5 (95% CI: 2.4–53.8)). All 11 thyrotoxic crisis cases were malignant melanoma patients, of which seven occurred under ICI combination therapy. Conclusions Thyroid dysfunction may occur after ICI therapies, and severe thyrotoxic crisis may even occur. Raising awareness of ICI-associated thyroid dysfunction can improve the detection and treatment of these diseases.