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Immune checkpoint inhibitor-associated pituitary adverse events: an observational, retrospective, disproportionality study

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Abstract

Purpose

The aim of this study was to identify and characterize immune checkpoint inhibitors (ICIs)-associated pituitary adverse events (AEs).

Methods

This is a retrospective disproportionality study based on VigiBase, the World Health Organization (WHO) global database of individual case safety reports (ICSRs), with a study period from January 1, 2011 to March 6, 2019. Information component (IC) and reporting odds ratio (ROR) are measures of disproportionate analysis. IC was used to evaluate the association between ICIs and pituitary AEs, while ROR was used to evaluate the differences in reporting of pituitary AEs between different ICI subgroups.

Results

The following ICI-associated pituitary diseases have been increasingly reported: hypophysitis (835 reports; information component 6.74 [95% CI 6.63–6.83]), hypopituitarism (268; 6.12 [95% CI 5.92–6.27]), pituitary enlargement (28; 5.19 [95% CI 4.57–5.63]). The anti-CTLA-4 subgroup had a stronger association with hypophysitis/hypopituitarism than the anti-PD (anti-PD-1 or anti-PD-L1) subgroup (ROR 8.0 [95% CI 6.7–9.6]). Among ICI-associated hypophysitis/hypopituitarism cases, the proportion of male was higher than female (630 [63.9%] vs 356 [36.1%]). Anti-CTLA-4 subgroup and ICI combination (nivolumab plus ipilimumab) subgroup both had a significantly earlier onset time than anti-PD subgroup (67 days [IQR 48–87]; 90 [IQR 34–155]; 140 [IQR 62–218], both p < 0.05). Other endocrinopathies that co-occurred with hypophysitis/hypopituitarism were adrenal insufficiency, thyroid dysfunction, diabetes mellitus and diabetes insipidus. Gastrointestinal disorder was the most common concurrent disease except for endocrinopathies.

Conclusions

ICI-associated pituitary adverse events have significantly increased, and their clinical characteristics should be kept in mind by oncologists and endocrinologists who manage patients treated by immunotherapy.

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Acknowledgements

The supplied data originated from various sources from VigiBase, and the probability that the suspected adverse effect is drug related is not the same in all cases. The information does not represent the opinion of the UMC or the World Health Organization. Camilla Westerberg of the custom search team at the Uppsala Monitoring Centre (Uppsala, Sweden) research department is acknowledged for his help with data extraction.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Author notes

  1. X. Bai and X. Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze, Quanzhou, Fujian, China

    X. Bai, X. Chen, X. Wu, Y. Huang, Y. Zhuang, Y. Chen, C. Feng & Xiahong Lin

  2. Department of Medical Administration, Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze, Quanzhou, Fujian, China

    Xiahong Lin

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Bai, X., Chen, X., Wu, X. et al. Immune checkpoint inhibitor-associated pituitary adverse events: an observational, retrospective, disproportionality study. J Endocrinol Invest 43, 1473–1483 (2020). https://doi.org/10.1007/s40618-020-01226-4

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