Inflammatory bowel disease associated with the combination treatment of nivolumab and metformin: data from the FDA adverse event reporting system
PD-1/PD-L1 inhibitors have demonstrated unparalleled therapeutic efficacy in multiple tumor types. Additionally, metformin has been linked to favorable outcomes in tumors. Many researchers have reported immune-mediated adverse events induced by immune checkpoint inhibitors (ICI) single agent. However, little is documented on the adverse events of the combined use of ICI and metformin.
To address this question, we used the Food and Drug Administration Adverse Event Reporting System (FAERS) to display the landscape of adverse events associated with the combined use of ICI and metformin. We identified 38 adverse event cases about the combination treatment between January 1, 2015 and June 30, 2018.
There are 36 cases in patients receiving nivolumab plus metformin (NM) therapy, and the other 2 cases were pembrolizumab plus metformin (PM). Among the 36 patients receiving NM therapy, the most common indication was for treatment of malignant lung cancer (20, 55.56%), Notably, 9 cases of inflammatory bowel disease (IBD) and diarrhea were reported.
Our findings revealed that higher risk of IBD might occur in lung cancer patients during the combined therapy of nivolumab plus metformin. Further studies are needed to verify our findings.
KeywordsImmune checkpoint inhibitors Metformin Adverse event FAERS Inflammatory bowel disease
Wenfeng Fang, Shaodong Hong, Gang Chen, Shen Zhao, Xi Chen, Zhonghan Zhang (all with the Sun Yat-sen University Cancer Center), provided data interpretation and critical revision of the manuscript. Yunpeng Yang, Yuanyuan Zhao, Yan Huang, and Hongyun Zhao (all with the Sun Yat-sen University Cancer Center), contributed excellent work to the conception and design of the study. None of these individuals received financial compensation.
LZ supervised this work. HZ, JL, YZ were responsible for the conception and design of the study, interpretation of data, drafting, and writing of the article. All authors participated in final approval of the article and agreed to be accountable for all aspects of the work.
This work was supported by: National Key R&D Program of China (Grant No. 2016YFC0905500, 2016YFC0905503). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Compliance with ethical standards
Ethics approval and consent to participate
Institutional review board approval was waived for this study because FAERS is a public anonymized database.
Conflict of interest
The authors declare that they have no conflict of interest.
- 4.FDA Adverse Event Reporting System (FAERS). http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/default.htm. Accessed 8 Aug 2018