W1116 Evidence That PPI Withdrawal May Exacerbate Symptoms and Increase Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease

Abstract

Background: A recent study has shown that proton pump inhibitor (PPI) therapy induces acid-related symptoms in healthy volunteers after PPI withdrawal. Rebound acid hypersecretion (RAHS) is believed to arise from the trophic effects of the PPI-induced hypergastrinemia on the oxyntic mucosa, lasting 4-8 weeks after discontinuing the PPI therapy. Aims: To assess whether PPI withdrawal may exacerbate reflux symptoms and increase esophageal acid exposure in patients with gastroesophageal reflux disease (GERD). Methods: Patients consecutively investigated for GERD with a validated symptoms questionnaire and 24h pH monitoring off PPI had their data revised from a prospectively constructed database. Heartburn and regurgitation in the last week before pH monitoring were scored between 0 (no symptom) and 5 (worst). GERD was defined according to Montreal criteria. Patients were classified as “naive to PPI therapy” (group 1) or “studied after discontinuing regular use of PPI”, which were reclassified according to the interval in days between PPI withdrawal and pH monitoring: 7-10 (group 2), 11-20 (group 3), and 21-90 (group 4). Results: Among 329 patients investigated for GERD (age 47 ± 15 years, 64% women, BMI 26 ± 3.8 kg/m2), those who discontinued PPI either between 7-10 days or 11-20 days scored higher for symptoms than groups 1 (naive to PPI, P < 0.001) and 4 (21-90 days, P < 0.05). Acid exposure was higher only in patients who discontinued PPI between 11-20 days, in comparison with groups 1 (naive do PPI, P < 0.05) and 4 (21-90 days, P < 0.01). When analyzing GERD patients (n = 249, figure), those who discontinued PPI between 7-10 days scored higher for symptoms compared to groups 1 and 4, whereas acid exposure was higher only in patients evaluated after 11-20 days of PPI withdrawal. Conclusions: This study suggests that PPI withdrawal may exacerbate reflux symptoms and increase acid exposure in patients with GERD. Symptoms were more remarkable soon after (7-10 days) discontinuation of PPI, whereas increased acid reflux had a later peak at 11-20 days, followed by attenuation of both symptoms and acid exposure. Whether these findings are related with a sequence of events starting with RAHS and ending with a protective response of the esophagus needs to be addressed.