Editorial: do we have a new addition to our GERD treatment tool box?

Abstract

The main goals of treatment for gastroesophageal reflux disease (GERD) continue to be relief of symptoms, healing and maintenance of remission of erosive oesophagitis when present, to prevent complications and ultimately to improve the patient's quality of life. Independent of mucosal findings at endoscopy, relief of symptoms is paramount to successful outcomes. For close to two decades, the mainstays of treatment have been delayed and dual-delayed release proton pump inhibitors (PPIs) given in daily or higher doses. While the number of hours the intragastric pH is >4 is correlated with erosive esophagitis healing,1 demonstrating improvement in symptoms with increased acid suppression has been elusive. In fact, showing clinically important increases in healing of erosive esophagitis with increased acid suppression with newer once daily delayed-release PPIs has been difficult. Potassium competitive acid blockers (P-CAB) are agents that not only inhibit gastric hydrogen potassium ATPase; unlike current PPIs, they inhibit the enzyme in a potassium competitive and reversible manner.2 Development of these agents has been hampered by side effects (principally liver) and inability to demonstrate significantly improved outcomes (healing or symptom relief) compared to currently available PPIs.3 This is unfortunate because as a class, they offer a more rapid onset of pH control than delayed-release PPIs and greater acid suppression over a 24-h period. Vonoprazan is a P-CAB in development. Phase 1 and 2 trials have shown a favourable safety profile, rapid onset of intragastric pH control (first dose) and superb healing of erosive oesophagitis.4, 5 In this study,6 Vonoprazan 20 mg daily was compared to lansoprazole 30 mg daily in healing of erosive esophagitis at 2, 4 and 8 weeks followed by a 1-year maintenance trial with 10 and 20 mg once daily. The authors evaluated healing in CYP2C19 extensive and poor metabolisers as well as serum gastrin, pepsinogen 1 and 2 and traditional adverse reactions. This new agent was demonstrated to be non-inferior to lansoprazole at all time points. Of interest, though not a primary endpoint, healing rates were statistically better than lansoprazole at the 2-, 4- and 8-week time frame. This was particularly evident in grades C and D and by a small margin in extensive metabolisers. Healing was maintained in over 90% at 1 year. One issue of concern is that no symptom data are presented despite the fact that it was collected. This raises concern that symptom relief was no different than lanzoprazole. Even though it was a secondary endpoint, we would have liked to have seen this data. It is difficult to get overly excited about this agent given the superb results and excellent safety profile obtained with currently available PPIs. What is needed are appropriately designed symptom studies that show more rapid and/or sustained improvement by P-CAB compared to currently available agents. We would hope this would be true, given the rapid onset of action and sustained control of intragastric pH offered by this agent. If this improvement in symptom relief can be demonstrated, vonoprazan offers potential for on-demand or intermittent use in GERD patients. This would indeed be a valuable addition to our GERD treatment tool box. Declaration of personal and funding interests: None.