Gastrointestinal adverse events related to monoclonal antibodies: A comprehensive evaluation of data from the FDA Adverse Event Reporting System database

Abstract: BACKGROUND: Monoclonal antibodies (mAbs) are frequently used in the treatment of various types of cancer and autoimmune diseases, but their causal association with Gastrointestinal (GI) disorders is still unclear. The purpose of this study is to evaluate the frequency and nature of GI adverse events (AEs) associated with mAbs reported in the FDA Adverse Event Reporting System (FAERS) database. OBJECTIVES: The study’s primary objective was to investigate the GI-AEs linked with mAbs, determine the demographic trends, and evaluate the clinical characteristics (age groups, seriousness, fatality, etc.) from the reported cases. Secondary objectives included using disproportionality signal analysis to find mAb-AEs combinations with significant associations. MATERIALS AND METHODS: Cases involving mAbs from the FAERS database were examined for the period from first authorization until June 30, 2023. The AEs were taken from the “GI Disorders” System Organ Class as standardized Preferred Terms. The characteristics of the cases, such as gender, age, seriousness, and co-suspect drug usage, were examined in detail. Proportional relative risk, IC025, χ 2 , and Ncomb metrics were used in disproportionality analysis to find the meaningful associations between a particular mAb and GI-AE. RESULTS: A total of 115,346 cases were evaluated, and the most common GI-AEs were caused by rituximab, bevacizumab, and denosumab. Constipation, vomiting, nausea, abdominal pain, and diarrhea were the most commonly reported AEs. 89.17% of cases had serious AEs, and 14.33% had fatal outcomes. Bevacizumab, atezolizumab, and rituximab had the highest death rates. 29 signals were detected by performing the disproportionality analysis for mAbs-GI-AEs combinations having significant values, especially for enterocolitis, ascites, GI perforation, and some other AEs as well, from GI disorders. The highest number of signals was identified by bevacizumab. CONCLUSIONS: This study highlights the strong correlation between mAbs and GI disorders, especially for mAbs such as atezolizumab, rituximab, and bevacizumab. The results emphasise the necessity of increased pharmacovigilance to keep an eye on these AEs and enhance patient safety. Improving patient safety during mAb therapy requires constant safety surveillance and additional research. Further investigation into the mechanisms underlying these relationships could lead to more effective management options for patients undergoing mAb therapy.