Timing and Predictors for Vonoprazan Dose Escalation in Refractory Gastroesophageal Reflux Disease: A Long-Term Observational Study.

Background: Vonoprazan (VPZ) therapy has become one of the standard treatments for gastroesophageal reflux disease (GERD). When GERD symptoms persist despite the maintenance dose therapy (10 mg daily), dose escalation to 20 mg daily is generally recommended. This study aims to clarify the proper timing and predictors for dose escalation of VPZ therapy in patients with refractory GERD treated with the maintenance dose.

Methods: This retrospective observational study included 257 patients with symptomatic GERD. Data from medical records, including endoscopic findings and Izumo scale scores, were analyzed.

Results: The mean follow-up period was 3.3 years. Throughout the follow-up period, VPZ dose escalation (from 10 to 20 mg daily) was required in 56 of 257 patients (22%). Kaplan-Meier analysis showed cumulative dose-escalation-free rates at 6 months, 1 year, and 2 years were 87%, 81%, and 78%, respectively. Predictive factors for VPZ dose escalation were analyzed using a Cox proportional hazards regression model. Multivariate analysis revealed that pre-existing epigastric pain was a significant positive predictor for dose escalation, whereas pre-existing constipation was identified as a significant negative predictor. Kaplan-Meier analysis indicated that the one-year dose-escalation-free rates were 69% in patients with epigastric pain compared to 88% in those without (p=0.001). GERD symptom scores showed a significant improvement one month after dose escalation.

Conclusion: The incidence of refractory GERD requiring VPZ dose escalation is relatively low. Epigastric pain prior to VPZ initiation independently predicts the need for dose escalation. VPZ dose escalation effectively improves GERD symptoms.