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Endocrine

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Open Access 01-09-2020 | Hypoparathyroidism | Original Article

Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: a disproportionality analysis using the WHO adverse drug reaction database, VigiBase

Authors: Xuefeng Bai, Xiahong Lin, Kainan Zheng, Xiaoyu Chen, Xiaohong Wu, Yinqiong Huang, Yong Zhuang

Published in: Endocrine | Issue 3/2020

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 anti-CTLA-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.

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Title: Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: a disproportionality analysis using the WHO adverse drug reaction database, VigiBase
Authors: Xuefeng Bai
Xiahong Lin
Kainan Zheng
Xiaoyu Chen
Xiaohong Wu
Yinqiong Huang
Yong Zhuang
Publication date: 01-09-2020
Publisher: Springer US
Keywords: Hypoparathyroidism
Hyperthyroidism
Hypopituitarism
Diabetes
Hypophysitis
Checkpoint Inhibitors
Type 1 Diabetes
Published in: Endocrine / Issue 3/2020
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-020-02355-9

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