Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non-erosive reflux disease

Background: The real size of the gastro‐oesophageal reflux disease (GERD) populationnot responding to proton pump inhibitor (PPI) therapy has still not been fullyelucidated. Causes of PPI refractoriness include incorrect diagnosis and lack ofadherence to therapy, in terms of incorrect dosage and timing.Aims: To evaluate the prevalence of refractoriness to optimal PPI therapy and thecontribution of non‐erosive reflux disease (NERD), reflux hypersensitivity, and functionalheartburn, to PPI refractoriness. The association of functional GI symptoms innon‐responders patients was evaluated.Methods: Frequency and severity of GERD symptoms (heartburn, regurgitation,chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowelsyndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated inpatients previously classified as non‐responders. Patients with at least one of theoesophageal symptoms with a frequency ≥3 /week were treated with esomeprazole40 mg once daily for 8 weeks and then re‐evaluated. Non‐responders (patients withoesophageal symptoms ≥3 times per week) underwent 24 hour multichannel intraluminalimpedance‐pH monitoring.Results: Of 573 consecutive patients, 92 with oesophageal symptoms and classifiedas PPI refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastricpain, and post‐prandial distress episodes were associated with a poor responseon multivariate analysis. NERD, reflux hypersensitivity, and functional heartburnpatients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group.Conclusions: True refractoriness in patients with GERD symptoms attending a secondarycare setting is lower than previously reported. Following a careful historyand optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutesonly a third of the PPI‐refractory group