COMPARING VONOPRAZAN TO HIGH-DOSE PROTON PUMP INHIBITORS FOR REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE.

Background: Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that significantly affects quality of life. Although proton pump inhibitors (PPIs) remain the primary pharmacological therapy, a considerable proportion of patients continue to experience persistent symptoms despite optimized or high-dose treatment, resulting in refractory GERD. Potassium-competitive acid blockers, particularly vonoprazan, have recently emerged as an alternative therapeutic option capable of producing rapid and sustained gastric acid suppression. Objective: To compare the effectiveness of vonoprazan with high-dose proton pump inhibitors in achieving sustained symptomatic remission among patients with refractory gastroesophageal reflux disease. Methods: A prospective randomized comparative study was conducted over four months in gastroenterology clinics in the Islamabad–Rawalpindi region. Adult patients with persistent reflux symptoms despite twice-daily high-dose PPI therapy were enrolled and randomly assigned to receive either vonoprazan (20 mg once daily) or continued high-dose PPI therapy. Symptom severity and disease-related quality of life were assessed using validated instruments including the Reflux Disease Questionnaire (RDQ) and the Gastroesophageal Reflux Disease–Health-Related Quality of Life (GERD-HRQL) questionnaire at baseline and during follow-up. Sustained symptomatic remission and time to remission were evaluated. Data were analyzed using parametric statistical tests with a significance level of p < 0.05. Results: A total of 72 participants completed the study. Sustained symptomatic remission was achieved in 69.4% of patients receiving vonoprazan compared with 41.7% in the high-dose PPI group (p = 0.017). The mean time to remission was significantly shorter with vonoprazan (3.1 ± 1.2 weeks) compared with high-dose PPI therapy (5.4 ± 1.6 weeks; p < 0.001). Greater improvements were also observed in symptom severity and quality-of-life scores, with RDQ scores decreasing from 21.6 to 7.4 in the vonoprazan group versus 21.2 to 12.8 in the PPI group. Conclusion: Vonoprazan demonstrated superior efficacy compared with high-dose proton pump inhibitors in achieving sustained symptomatic remission and improving quality of life in patients with refractory GERD. These findings support the potential role of vonoprazan as an effective therapeutic alternative for patients with persistent reflux symptoms despite conventional treatment. Keywords: Esophagitis; Gastroesophageal Reflux; Gastroesophageal Reflux Disease; Proton Pump Inhibitors; Quality of Life; Randomized Controlled Trial; Vonoprazan