Introduction
Erosive esophagitis, the primary endoscopic manifestation of gastroesophageal reflux disease (GERD), is characterized by inflammatory injury of the esophageal mucosa resulting from chronic reflux of gastric contents. Clinically, patients present with heartburn and regurgitation that substantially impair health-related quality of life, and persistent mucosal injury may progress to esophageal stricture, Barrett's esophagus, and esophageal adenocarcinoma. Although proton pump inhibitors (PPIs) remain the guideline-recommended first-line therapy, the 2022 American College of Gastroenterology guideline recognizes that mild mucosal breaks classified as Los Angeles (LA) grade A may be difficult to distinguish reliably from normal mucosal variations. Nevertheless, many previous clinical trials enrolled substantial numbers of patients with LA grade A esophagitis, which may have diluted the assessment of treatment efficacy in patients with clinically meaningful mucosal injury. Consequently, there remains a need for adequately powered clinical trials focusing on patients with moderate-to-severe erosive esophagitis to rigorously evaluate the mucosal healing efficacy of novel acid-suppressive therapies.
Aims & Methods
To evaluate the efficacy and safety of anaprazole, a novel proton pump inhibitor, compared with rabeprazole in adults with endoscopically confirmed Los Angeles (LA) grade B-D erosive esophagitis. In this multicenter, randomized, double-blind, double-dummy, active-controlled, phase III noninferiority trial, 500 patients were randomized 1:1 to receive anaprazole 60 mg once daily or rabeprazole 20 mg once daily for up to 8 weeks. Enrollment was prospectively stratified to require ≥20% LA grade C or D disease. The primary endpoint was cumulative endoscopic healing through 8 weeks. Secondary endpoints included the week-4 healing rate, symptom improvement, and changes in GERD-HRQL scores. Safety was assessed in all patients who received at least one dose of study medication.
Results
Of 585 patients screened, 500 underwent randomization (250 per group). The full analysis set comprised 467 patients (anaprazole, n=233; rabeprazole, n=234). Baseline characteristics were well balanced; all patients had LA grade B-D disease, with 20.2% and 20.5% having LA grade C/D disease in the anaprazole and rabeprazole groups, respectively. The primary endpoint was met: cumulative healing rates at week 8 were 88.4% versus 84.6% (adjusted risk difference, 3.8%; 95% confidence interval [CI], -2.3 to 10.0), demonstrating noninferiority (margin -10%). Consistent findings were observed in the per-protocol population (93.9% vs. 89.4%; risk difference, 4.8%; 95% CI, -0.4 to 10.0). Week-4 healing rates were 77.3% and 73.9%, respectively. Improvements in reflux symptom frequency were comparable between groups, including overall reflux (90.3% vs. 87.5%) and heartburn (92.6% vs. 93.4%), as were reductions in GERD-HRQL scores. Treatment-emergent adverse events occurred in 49.4% and 52.9% of patients, respectively; no treatment-related serious adverse events or deaths were reported.
Conclusion
Anaprazole 60 mg once daily was noninferior to standard-dose rabeprazole in achieving cumulative endoscopic healing through 8 weeks in adults with LA grade B-D erosive esophagitis, with comparable symptom relief, quality-of-life improvements, and safety.
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Disclosure
The authors declare no conflicts of interest.