Adverse Reactions With VEGF Inhibitors in Combination With NSAIDs: Disproportionality Analysis Using JADRE and FAERS.

Objective: The concurrent use of vascular endothelial growth factor (VEGF) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) raises concerns regarding the increased risk of adverse drug reactions (ADRs) due to potential pharmacodynamic interactions. However, no studies have specifically addressed this issue. The objective of this study was to investigate whether the combination of these drugs increased the risk of ADRs.

Methods: Disproportionality analysis was conducted on ADR reports from the Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS) databases. The concomitant signal score and Ω shrinkage measure were used to identify safety signals associated with the drug combination. Additionally, logistic regression analysis focused on reports of ADRs related to cancer treatment and assessed the significance of the adjusted reporting odds ratio (aROR) for the interaction between these drugs.

Results: Disproportionality analysis included ADR data from the JADER (n=1,509,399) and FAERS (n=38,610,433) databases. The concomitant signal score and Ω shrinkage measure identified a signal for gastrointestinal perforation in both databases. Logistic regression on cancer treatment-related ADRs (JADER: n=255,177; FAERS: n=1,167,941) showed a synergistic increase in gastrointestinal perforation risk with the drug combination [aROR for interaction term: JADER: 1.74 (95% confidence interval (CI)=1.45-2.07); FAERS: 1.49 (95% CI=1.29-1.72)].

Conclusions: The combination of VEGF inhibitors and NSAIDs is associated with an increased risk of gastrointestinal perforation, a serious and potentially fatal ADR. Therefore, caution is warranted when prescribing a combination of these drugs.