PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis

Background Symptomatic response to proton pump inhibitor (PPI) therapy in patients with non-erosive reflux disease (NERD) is often reported as lower than in patients with erosive reflux disease (ERD). However, the definition of NERD differs across clinical trials. This meta-analysis aims to estimate the rate of symptom relief in response to PPI in NERD patients. Methods MEDLINE (19662010), Cochrane Comprehensive Trial Register (19972010) and EMBASE (19852010) databases were searched and manual searches from studies references were performed. Randomized clinical trials were selected that included patients with heartburn, and analyzed the effect of short-term PPI treatment. The primary outcome of selected studies was defined as complete or partial heartburn relief. Two reviewers independently extracted data and assessed study quality of selected articles. Random effects models and meta-regression were used to combine and analyze results. Key Results The pooled estimate of complete relief of heartburn after 4 weeks of PPI therapy in patients with ERD was 0.72 (95% CI 0.690.74) (32 studies), vs 0.50 (0.430.57) (eight studies) in empirically treated patients, 0.49 (0.440.55) (12 studies) in patients defined as non-erosive by negative endoscopy, and 0.73 (0.690.77) (two studies) in patients defined as non-erosive by both negative endoscopy and a positive pH-test. Conclusions & Inferences In well-defined NERD patients, the estimated complete symptom response rate after PPI therapy is comparable to the response rate in patients with ERD. The previously reported low response rate in studies with patients classified as NERD is likely the result of inclusion of patients with upper gastrointestinal symptoms that do not have reflux disease.