Comparing the Efficacy and Safety of Fexuprazan and Lansoprazole for the Prevention of Nonsteroidal Anti-inflammatory Drug-Induced Peptic Ulcer

Abstract

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.

Fig. 1

Distribution of patients. NSAID, nonsteroidal anti-inflammatory drug.

Fig. 2

Common risk difference in the incidence of esophagogastroduodenoscopy-confirmed peptic ulcer for 24 weeks of treatment. The main analysis and sensitivity analysis were carried out using a full-analysis set. PPS, per-protocol set; CI, confidence interval.

Fig. 3

Patient-reported symptoms based on the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). (A) Least-square (LS) mean changes in symptom scores. (B) Proportion of patients with resolution or development of symptoms based on changes in symptom scores. The bars on the right side of each graph represent the proportions of patients whose PAGI-SYM symptom score increased by at least 1 from 0 at baseline, whereas the bars on the left side represent the proportions of patients whose PAGI-SYM symptom score changed to 0 from positive numbers at baseline. EOT, end-of-treatment.