From reflux to eosinophilic esophagitis: broadening the scope of P-CAB therapy. At what price?

Potassium-competitive acid blockers (P-CABs) provide more rapid, profound, and sustained gastric acid suppression than conventional proton pump inhibitors (PPIs) and are increasingly used for acid-related disorders. Emerging evidence from Japan suggests that vonoprazan may also be effective in eosinophilic esophagitis (EoE), where PPIs are already established first-line therapy. However, comparative studies have thus far shown broadly similar symptomatic, endoscopic, and histological responses with P-CABs and PPIs, suggesting that antisecretory potency alone may not determine therapeutic efficacy. Anti-inflammatory and epithelial protective actions, well established for PPIs and increasingly recognized experimentally for P-CABs, may also contribute. Against this background, Kobayashi and colleagues report in this issue an association between P-CAB use and esophageal candidiasis in a heterogeneous patient population undergoing diagnostic upper gastrointestinal endoscopy. Importantly, however, their findings do not establish a greater risk with P-CABs than with PPIs; rather, the comparable effect estimates for both drug classes, together with the independent association with atrophic gastritis, support profound acid suppression itself as a potential determinant of susceptibility to Candida infection. This issue may be particularly relevant in EoE, where impaired epithelial barrier function, altered esophageal microbial ecology, and concomitant swallowed topical corticosteroid therapy may create a permissive environment for fungal overgrowth. The ongoing randomized trial of vonoprazan in Western patients with EoE should better define both efficacy and safety in this setting. Thus, extending P-CAB therapy from reflux disease to EoE represents an intriguing therapeutic opportunity, but one whose incremental benefit must ultimately be weighed against the biological consequences of increasingly powerful acid suppression.