Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2026
Real-world hepatic safety of the potassium-competitive acid blocker: A RUCAM-adjudicated multicenter cohort study.
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Chon Hye Yeon, Yun Hae-Ryong, Jung Da Hyun, Lim Jeonghyun, Gwon So Hyeon, Son Nak-Hoon, Youn Young Hoon, Huh Cheal Wung
Аннотация
BACKGROUND & AIMS: Early-generation potassium-competitive acid blockers (P-CABs) were withdrawn during clinical development because of hepatotoxicity, and long-term real-world hepatic safety data for newer P-CABs remain scarce.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 intervals. No case exceeded the "possible" RUCAM threshold.
CONCLUSIONS: No increased risk of RUCAM-possible DILI was detected for tegoprazan compared with PPIs or H2RAs, although the small number of events precludes a conclusion of equivalent safety. The rarity of RUCAM-possible events across all acid-suppressive drug classes raises the possibility that previously reported signals may partly reflect differences in outcome ascertainment.
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 intervals. No case exceeded the "possible" RUCAM threshold.
CONCLUSIONS: No increased risk of RUCAM-possible DILI was detected for tegoprazan compared with PPIs or H2RAs, although the small number of events precludes a conclusion of equivalent safety. The rarity of RUCAM-possible events across all acid-suppressive drug classes raises the possibility that previously reported signals may partly reflect differences in outcome ascertainment.