An upcoming new class of acid secretion inhibitors called potassium-competitive acid blockers (P-CAB) which competitively inhibits the binding of potassium ion to H+, K+-ATPase (proton pump) in the final step of gastric acid secretion in gastric parietal cells will apparently represent a better gastric acid control. Nevertheless, it is well known that GERD symptoms hardly correlate with the extension of gastric acid control. By contrast, it is also known that there is a direct correlation between acid inhibition and mucosal healing rates. On the other hand, most of our GERD patients are known to be NERDs.
Given the peculiar PK behavior of P-CABs, clinically reflected in the 24H pHmetric median intragastric pH, it seems that a 20-40mg o.d. is enough to achieve a superior 24H IG pH profile to regular PPIs at standard doses. Multiple considerations should be taking into account such as efficacy/safety ratio, pharmacoeconomics, ideal patient selection, etc.before we, as clinicians, adopt these new compounds.
Given the afore mentioned P-CABs characteristics, should we move on to substitute the regular PPIs for these new compounds, or should we try to combine them as "first 2-4 weeks w/P-CABs, followed by next 4-8 weeks w/standard PPIs, or should we reserve these new compounds only for the "difficult to treat" patients?
Yet there are variations in symptoms control with 2nd and 3rd line PPI’s and some limited evidence for combining PPI and H2A.
You are right that symptom control and “acid” control as measured by ph studies are different outcome measures that don’t necessarily correlate. It will be interesting to see the acid results of these drugs
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