Editorial: P‐CABs for treatment of reflux oesophagitis—is this the future?

Proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive oesophagitis, peptic ulcer disease and Helicobacter pylori infection for over 25 years.1 Although PPIs are highly effective, there is room for pharmacologic optimization. For example, symptoms of gastrooesophageal reflux are not maximally improved with the initial dose or asneeded doses of PPI, with 3 to 5 days required to reach maximal effect.2,3 Patients may have breakthrough symptoms at night due to failure to control nocturnal gastric acid secretion. Additionally, PPIs generally require a mealstimulated acidic environment for activation and are subject to the effects of CYP2C19 genetic polymorphisms.2 Finally, the longterm safety profile of PPIs remains an area of debate. Compared to PPIs, potassiumcompetitive acid blockers (PCABs) have longer halflives, are stable in acidic environments, are not affected by CYP2C19 polymorphisms, and reach full effect after the first dose.4– 6 In the doubleblind, multicentre study by Cho et al, performed in 351 patients, tegoprazan was noninferior to lansoprazole for maintaining endoscopic remission of healed erosive oesophagitis for a 12– 24 week period.7 Moreover, this occurred with significantly fewer drugrelated side effects than lansoprazole (12.7% vs. 21.3%, p = 0.03) without differences in gastrin, pepsinogen I or II, or a decrease in B12, folate, iron or magnesium. However, several caveats must be considered. First, only 5%– 6% of patients initially had Los Angeles (LA) grade C/D oesophagitis. As we taper enthusiasm for the significance of LA grade A/B oesophagitis, the results of an important indication for treatment are lacking. Second, as a Korean population, a loss of function CYP2C19 mutation yielding higher levels of PPI is likely to be significantly higher than in the Western population where a gain of function mutation is more common.8,9 In other words, the halflife for lansoprazole in the Korean population will be longer in this study than in the West. This might explain why 15 mg of lansoprazole was used as opposed to 30 mg which is more likely to be used in the West. Thus, the global relevance of this study is attenuated. The ultimate question is what will be the place for PCABs in the PPI era? Will they be used for patients with highgrade erosive oesophagitis unresponsive to PPIs, particularly those who are CYP2C19 hypermetabolizers? Will the benefits of oncedaily dosing, faster loading and better ondemand therapy make them the firstline medication? Similarly, will the reported side effects ostensibly related to acid suppression such as B12 and iron malabsorption, elevated serum gastrin, enterochromaffinlike cell hyperplasia and gastric atrophy increase with longterm use when compared to PPIs? Remember— when omeprazole was launched, it could not be used for more than 8 weeks! We are fortunate to have two classes of gastric acidsuppressing medications from which to choose that are far more potent than any drug we have had previously. Let's leave it at that for now.