Comparative Reporting Patterns of Rabeprazole and Other Proton Pump Inhibitors in EudraVigilance: A System Organ Class-Level Disproportionality Analysis

Background/Objectives: Rabeprazole differs from other proton pump inhibitors (PPIs) in its activation and lower dependence on CYP2C19. We compared its System Organ Class (SOC)-level reporting profile with those of esomeprazole, pantoprazole, omeprazole and lansoprazole in EudraVigilance individual case safety reports (ICSRs). Methods: Aggregated ICSR counts were retrieved from adrreports.eu (data lock point 4 October 2026). Rabeprazole was compared head-to-head with each comparator using reporting odds ratios (RORs) with 95% confidence intervals across 27 MedDRA SOCs, with Benjamini–Hochberg false discovery rate control over all 108 tests. Bonferroni correction and serious-only analyses were sensitivity analyses; female-only and male-only analyses were exploratory. Results: Of 232,045 ICSRs, 7960 involved rabeprazole. Hepatobiliary disorders were the only SOC reported more often with rabeprazole than with all four comparators (ROR 1.29–1.96); the excess met the Bonferroni threshold and persisted among serious reports (ROR 1.19–1.97) and in both sexes. Skin and subcutaneous tissue disorders were reported more often than with three comparators and, among serious reports, than with all four (ROR 1.14–1.83). Eight SOCs showed consistently lower reporting odds, alongside fewer SOCs per rabeprazole ICSR and a different reporter mix. Conclusions: Rabeprazole showed a consistent hepatobiliary reporting signal within the PPI class, in line with earlier FAERS findings. This is a reporting signal, not a clinical signal: without exposure data, the results describe relative reporting, not incidence, comparative risk or causality, and lower reporting odds do not imply lower clinical risk.