Potassium-competitive Acid Blockers for Treatment of Extraesophageal Symptoms and Signs

Extraesophageal symptoms and signs of gastroesophageal reflux disease (GERD), such as throat clearing, globus sensation, hoarseness, cough, asthma, pulmonary fibrosis, otitis, sinusitis, and dental erosions, are common and pose diagnostic and therapeutic challenges. Proton pump inhibitors (PPIs) are the mainstay of treatment for GERD, but have demonstrated a limited effectiveness for extraesophageal symptoms and signs in several meta-analyses. Potassium-competitive acid blockers (P-CABs) offer more rapid and sustained acid inhibition than PPIs; therefore, P-CABs may have the potential to be at least as good or superior to PPIs in relieving extraesophageal symptoms and signs of GERD. To date, there have been 4 prospective randomized trials demonstrating similar efficacy of P-CABs to PPIs in the treatment of extraesophageal symptoms and signs, but more rapid and greater efficacy in patients with severe symptoms. Therefore, P-CABs appear to have a treatment role in extraesophageal symptoms and signs of GERD. However, considering that P-CABs are not superior to PPIs, large-scale, multi-center studies with double dose P-CABs over a prolonged period of time may elucidate a subgroup of patients in whom P-CABs are beneficial in ameliorating extraesophageal symptoms and signs.