Adverse reactions of immune checkpoint inhibitors combined with Proton pump inhibitors: a pharmacovigilance analysis of drug-drug interactions

作者：Xiayang Ren, Li Lu, Yiran Chen, Xiangli Cui, Rui Wan, Yanfeng Wang · 发表于：BMC Cancer · 年份：2024 · DOI：10.1186/s12885-024-12947-7 · 被引用次数：10 · 研究领域：Cancer Immunotherapy and Biomarkers、Pharmacovigilance and Adverse Drug Reactions、Advanced Causal Inference Techniques

BACKGROUND: Combining immune checkpoint and proton pump inhibitors is widely used in cancer treatment. However, the drug-drug interactions of these substances are currently unknown. This study aimed to explore drug-drug interactions associated with concomitant immune checkpoint and proton pump inhibitors. METHODS: Data were obtained from the US Food and Drug Administration Adverse Event Reporting System from 2014 to 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratios (RORs) with 95% confidence intervals (95%Cls). The adjusted RORs (RORadj) were then analysed using logistic regression analysis, considering age, sex, and reporting year. Drug-drug interactions occur when a combination treatment enhances the frequency of an event. Further confirmation of the robustness of the findings was achieved using additive and multiplicative models, which are the two statistical methodologies for signal detection of DDIs using spontaneous reporting system. RESULTS: The total number of reports on immune checkpoint combined with proton pump inhibitors was 4,276. Median patient age was 66 years (interquartile range [IQR]: 60-74 years). Significant interaction signals were observed for congenital, familial and genetic disorders (RORadj = 2.66, 95%CI, 1.38-5.14, additive models = 0.7322, multiplicative models = 3.5142), hepatobiliary disorders (RORcrude = 6.64, 95%CI, 5.82-7.58, RORadj = 7.10, 95%CI, 6.16-8.18, additive models = 2.0525, multiplicat...