The Ameliorating Effect of Switching to Vonoprazan: A Novel Potassium-Competitive Acid Blocker in Patients with Proton Pump Inhibitor Refractory Non-Erosive Reflux Disease

Abstract

Introduction: Weakly acidic reflux has been reported to be the major cause of symptoms in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) undergoing PPI treatment. We previously reported that reflux at pH 4–5 was the main factor that induced symptoms in such patients. The present study aimed to elucidate the symptom-ameliorating effect of vonoprazan (VPZ) by evaluating the change in the pH value of the refluxate using multichannel intraluminal impedance and pH (MII-pH) monitoring. Methods: We retrospectively evaluated the records of MII-pH monitoring in 29 symptom index (SI) and/or symptom association probability (SAP)-positive patients with PPI-refractory NERD. After switching to VPZ 20 mg/day, we performed MII-pH monitoring again. We assessed the change in the score of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the pH value of the refluxate, and the percent times of intragastric pH <4 or <5 before and after switching. We divided the patients into the following 2 groups according to the FSSG score after switching: effective and noneffective groups. Results: Among of the 29 SI/SAP-positive patients, 16 underwent switching to VPZ. Furthermore, of these 16 patients, 10 underwent MII-pH monitoring again after switching. The FSSG score decreased, the pH value of the refluxate increased, and the percent times of intragastric pH <4 or <5 reduced after switching when compared with the findings before switching. In the effective group, both the proportion of reflux at pH <4 and that of reflux at pH 4–5 decreased while taking VPZ when compared with the findings while taking double-dose PPI. In the noneffective group, the proportion of reflux at pH <4 decreased but that of reflux at pH 4–5 increased and that of reflux at pH <5 did not change overall while taking VPZ. In addition, the percent times of intragastric pH <5 values were low in the effective group. Conclusion: Symptom suppression appears to be inadequate in patients with persistent reflux at pH 4–5 even with VPZ 20 mg/day. Strong acid suppressive therapy with VPZ to increase the pH value of the refluxate to ≥5 is useful for symptom improvement.

Acid Suppressant Therapy: a Step Forward with Potassium-Competitive Acid Blockers

“…pH impedance recording revealed fewer reflux events at pH G5 in patients with symptom improvement compared to those without. In these patients, the proportion of reflux at pH G4 decreased but that of reflux at pH 4-5 increased while that of reflux at pH G5 did not change [84]. Despite the limitations of the study, the results suggest that the lack of symptom improvement is related to inadequate acid suppression that could be addressed by a higher vonoprazan dose.…”

“…This apparent resistance, however, could be dose-dependent. A retrospective, small study [84] evaluated NERD patients with symptoms resistant to double-dose PPIs, who were switched to vonoprazan (20 mg daily). pH impedance recording revealed fewer reflux events at pH G5 in patients with symptom improvement compared to those without.…”

ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro‐esophageal reflux disease

“…In a RCT of vonoprazan vs lansoprazole 30 mg daily, higher doses (20 mg, 40 mg daily) of vonoprazan were numerically superior (100% for 20 mg, 96% for 40 mg) to lansoprazole (93.5%) in healing LA C/D esophagitis after 8 weeks; the differences were greater, but still not statistically significant at the 2‐week time point (82.6% lansoprazole vs 96% for both doses of vonoprazan) 232 . Vonoprazan improves refractory GERD symptoms mainly by reducing acidic reflux episodes, but is not consistently effective, especially when reflux episodes with pH 4–5 persist 233 . The approved doses in Japan are 10 mg and 20 mg.…”

Review article: potassium‐competitive acid blockers for the treatment of acid‐related disorders

“…In patients non‐responsive to vonoprazan 20 mg once‐daily, symptom suppression was inadequate with persistent reflux at pH 4‐5. However in responsive subjects, vonoprazan increased the pH of the refluxate to above 5 and was associated with symptom improvement 33 …”

“…Weakly acidic reflux (pH 4‐5) may be a major cause of symptoms in patients with PPI‐refractory NERD 33 . In patients non‐responsive to vonoprazan 20 mg once‐daily, symptom suppression was inadequate with persistent reflux at pH 4‐5.…”