Comprehensive Analysis of Gastrointestinal Injury Induced by Nonsteroidal Anti-Inflammatory Drugs Using Data from FDA Adverse Event Reporting System Database

<b>Background/Objectives:</b> Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly associated with gastrointestinal (GI) adverse events. This study aimed to assess the incidence and patterns of NSAID-induced GI disorders using the FDA Adverse Event Reporting System (FAERS) database and to compare the risks among different NSAIDs. <b>Methods:</b> NSAID-related reports were extracted from FAERS, focusing on 21 ulcer-related GI events with ≥1000 reports each, based on MedDRA v26.0. The number of reports, reporting odds ratios, and <i>p</i>-values were calculated and visualized using a volcano plot. Principal component analysis(PCA) was carried out to reduce the dimensionality of the dataset and revealed under-lying patterns in the data.PCA was performed to identify patterns related to risk, severity, and injury site, whereas hierarchical clustering was used to group NSAIDs based on these patterns. Hierarchical cluster analysis is a method of grouping similar data to generate a classification. <b>Results:</b> Statistically significant signals were identified for 19 of the 21 GI-related adverse events, including the serious condition of perforation. PCA revealed that the first component represented risk, the second severity, and the third the site of injury (upper vs. lower GI tract). Cyclooxygenase-2 (COX-2) selective NSAIDs (e.g., celecoxib, rofecoxib) were associated with a lower incidence but greater severity, primarily in the upper GI tract. Conversely, nonselective NSAIDs (e.g., acetylsalicylic acid, lornoxicam) showed higher incidence rates, though the events were generally milder. In our dataset, acetylsalicylic acid had the highest incidence, whereas meloxicam showed the highest severity. Clustering analysis revealed three distinct NSAID groups with differing patterns in risk, severity, and affected GI site. Mild adverse events may be underreported in FAERS. Dosage-related effects were not assessed in this study. <b>Conclusions:</b> NSAIDs differ significantly in their gastrointestinal adverse event profiles, attributable to COX selectivity. When selecting an NSAID, both the likelihood and the nature of potential GI harm should be considered.