Ear and Labyrinth Toxicities Induced by Immune Checkpoint Inhibitors: A Disproportionality Analysis from 2014 to 2019

Abstract

Aim: We aimed to systematically characterize ear and labyrinth toxicities after immune checkpoint inhibitors (ICIs) initiation. Materials & methods: Data were extracted from the US FDA Adverse Event Reporting System database. Disproportionality analysis including information component and reporting odds ratio (ROR) was performed to access potential signals. Results: In FDA Adverse Event Reporting System database, 284 records for ICIs-associated ear/labyrinth adverse events (AEs) were involved. In general, there was no significant association between total ICIs use and total ear and labyrinth AEs (ROR₀₂₅: 0.576). However, in ICIs monotherapy and polytherapy groups, signals were detected in several specific ear and labyrinth AEs. Conclusion: Total ear and labyrinth toxicities were not significantly reported with ICI immunotherapy, while class-specific ear toxicities were detected in some strategies.

Keywords::

• disproportionality analysis
• ear and labyrinth toxicities
• FAERS database
• immune checkpoint inhibitors

Supplementary data

To view the supplementary data that accompany this paper, please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/imt-2019-0120

Author contributions

J He, F Hu and X Ye designed the study; F Hu, X Ye, Y Zhai and J Xu performed the data analysis; F Hu, J Xu, X Guo, Z Guo, X Zhou, M Wang and Y Ruan managed and checked all the data. All authors contributed to the manuscript writing equally. All authors read, checked and approved the final manuscript.

Acknowledgments

All the data used in the study were extracted from the FAERS database. The likelihood of a causal relationship is not the same in all reports. The conclusion in this study do not represent the opinion of the US FDA.

Financial & competing interests disclosure

This study was supported by: National Nature Science Foundation of China, grant/award number: 81703296; Fourth Round of Three-year Action Plan on Public Health Discipline and Talent Program: Evidence-based Public Health and Health Economics, grant/award number: 15GWZK0901; Shanghai Municipal Commission of Health and Family Planning Fund for Excellent Young Scholars, grant/award number: 2018YQ47; Nature Science Foundation of Shanghai, grant/award number: 18ZR1449500 and National Science and Technology Major Project, Grant/Award Number: 2017ZX09304030; National Thirteenth Five Year Plan Major Special Project (2017ZX09304016). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The datasets generated and/or analyzed during the current study are available in the FARES repository, [https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html]. All sensitive and individual clinical data were de-identified and all the data used in our study are available to the public (FAERS).

Additional information

Funding

This study was supported by: National Nature Science Foundation of China, grant/award number: 81703296; Fourth Round of Three-year Action Plan on Public Health Discipline and Talent Program: Evidence-based Public Health and Health Economics, grant/award number: 15GWZK0901; Shanghai Municipal Commission of Health and Family Planning Fund for Excellent Young Scholars, grant/award number: 2018YQ47; Nature Science Foundation of Shanghai, grant/award number: 18ZR1449500 and National Science and Technology Major Project, Grant/Award Number: 2017ZX09304030; National Thirteenth Five Year Plan Major Special Project (2017ZX09304016). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.