Real-world hepatic safety of the potassium-competitive acid blocker: A RUCAM-adjudicated multicenter cohort study
Abstract
BACKGROUND & AIMS
Early-generation potassium-competitive acid blockers (P-CABs) were withdrawn during clinical development because of hepatotoxicity, and long-term real-world hepatic safety data for newer P-CABs remain scarce. Drug-induced liver injury (DILI) ascertainment in observational studies is further limited by the reliance on nonspecific outcome definitions. We aimed to evaluate the hepatic safety of tegoprazan compared with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) using Roussel Uclaf Causality Assessment Method (RUCAM)-based adjudication.
METHODS
This large-scale, multicenter retrospective cohort study used a new-user, active-comparator design including users of tegoprazan, PPIs, or H2RAs with ≥30 cumulative defined daily doses (cDDDs). Propensity score matching (PSM) balanced demographics, comorbidities, hepatotoxic co-medications, and baseline liver biochemistry. The primary outcome was RUCAM-adjudicated DILI (score ≥3); hazard ratios (HRs) were estimated by Cox regression with Firth's penalized likelihood for rare events.
RESULTS
Of 363,340 screened patients, 11,190 were included; PSM yielded 5,586 (1,862/group). RUCAM-possible DILI was very rare, with 3, 2, and 3 events (0.17, 0.07, and 0.15 per 100 person-years) in the tegoprazan, PPI, and H2RA groups, respectively. No increased risk was detected for tegoprazan versus H2RAs (Firth-penalized HR 0.98; 95% CI, 0.20-4.95) or PPIs (HR 1.63; 95% CI, 0.28-9.56), with wide confidence…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 363,340 participants or records.
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