Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: a disproportionality analysis using the WHO adverse
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ORIGINAL ARTICLE
Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: a disproportionality analysis using the WHO adverse drug reaction database, VigiBase Xuefeng Bai1 Xiahong Lin ●
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Kainan Zheng3 Xiaoyu Chen1 Xiaohong Wu1 Yinqiong Huang1 Yong Zhuang1 ●
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Received: 12 March 2020 / Accepted: 15 May 2020 © The Author(s) 2020
Abstract Purpose Our study aimed to map endocrine toxicity spectrum of immune checkpoint inhibitors (ICIs). Methods We obtained data from VigiBase, between January 1, 2011 and March 6, 2019. All endocrine adverse drug reactions (ADRs) were classified by group queries according to the Medical Dictionary for Regulatory Activities. Disproportionality analysis was performed with information component (IC) and reporting odds ratio (ROR). We used IC to identify meaningful endocrinopathies associated with ICIs and ROR to compare differences between ICI subgroups of ADRs. IC025 (lower end of the 95% confidence interval of IC) is considered significant if larger than 0. Results In all, 6089 reports for endocrinopathies associated with ICIs were involved, with a male to female ratio of 1.5:1. The disproportionality analysis indicated significance of not only common endocrinopathies: thyroid dysfunction, hypophysitis/hypopituitarism, adrenal insufficiency, T1DM, fulminant T1DM (IC025: 4.12–6.62), but also rare endocrinopathies: hypoparathyroidism, diabetes insipidus, hypogonadism (IC025: 1.56–2.04). Increased risk of ADR reporting emerged in antiCTLA-4 (e.g., hypophysitis/hypopituitarism, adrenal insufficiency) or in anti-PD-1/PD-L1 (e.g., thyroid dysfunction, T1DM, fulminant T1DM). In general, combination therapy (anti-CTLA-4 plus anti-PD-1/PD-L1) had a stronger association with endocrinopathies than monotherapy (ROR: 2.8, 95% CI: 2.5–3.1). Onset time of common endocrinopathies differed between different ICI therapies, typically within 12 weeks in anti-CTLA-4 monotherapy but diffusely ranging from 0 to 48 weeks in anti-PD-1 monotherapy. Conclusions Our study shows rising reporting frequencies of endocrinopathies caused by ICIs, especially aggravated in combination therapy. Clinicians should be early aware of latent endocrine toxicity and different onset time of endocrinopathies when implementing ICI therapies. Keywords Immune checkpoint inhibitor Endocrine toxicity Endocrinopathy Immune-related adverse event Onset time ●
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Introduction Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02355-9) contains supplementary material, which is available to authorized users. * Xiahong Lin [email protected] 1
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze District, Quanzhou, Fujian Province, China
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Department of Medical Administration, The Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze District, Quanzhou, Fujian Province, China
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Data Mining Working Group, China Telecom Co., Lt
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