Background/aims: To compare the efficacy and safety of fexuprazan and lansoprazole for preventing peptic ulcers (PUs) induced by nonsteroidal anti-inflammatory drugs (NSAIDs).
Methods: This multicenter, double-blind, randomized, active-controlled study was conducted across 32 hospitals in South Korea. Patients with musculoskeletal disease requiring long-term treatment with celecoxib, naproxen, or meloxicam were randomized to receive either fexuprazan 20 mg/day (n=212) or lansoprazole 15 mg/day (n=211) for 24 weeks. The primary endpoint was the occurrence of PUs, which were confirmed via esophagogastroduodenoscopy (EGD), with a non-inferiority margin of 8.3%. Only ulcers that developed during the treatment period were examined in the analysis. The occurrence of gastroduodenal bleeding was also monitored via EGD, and symptoms were assessed by using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). Adverse events were recorded during the study.
Results: The incidence rate of EGD-confirmed PUs at week 24 was 1.16% in the fexuprazan group and 2.76% in the lansoprazole group, with a between-group difference of -1.64% (95% confidence interval, -4.52% to 1.25%), demonstrating non-inferiority. No patients presented with gastroduodenal bleeding. No significant between-group differences were found in the PAGI-SYM scores (leastsquare mean difference in the total score at week 24, -0.42; 95% confidence interval, -2.48 to 1.64; p=0.69). There were low rates of adverse drug reactions in the fexuprazan and lansoprazole groups (8.57% vs 4.78%, respectively p=0.12).
Conclusions: Given its non-inferiority to lansoprazole and similar safety profile, fexuprazan is a promising alternative for the prevention of NSAID-induced PUs (ClinicalTrials.gov identifier NCT04784910).
Keywords: Fexuprazan; Nonsteroidal anti-inflammatory drugs; Peptic ulcer; Phase III clinical trial.