The Mucosal Protection in the Treatment of Erosive Reflux Esophagitis: Mechanisms for Restoring Epithelial Permeability. A Randomized Clinical Trial.

Abstract

Background and aims: Gastroesophageal reflux disease (GERD) is widespread in the population and is characterized by the risk of developing Barrett's esophagus and associated adenocarcinoma. Key factors in the progression of the disease are not only the frequency and duration of reflux episodes, but also the resistance of the esophageal mucosa to aggressive reflux molecules. Assessment of the state of tight junction proteins, the rate of their recovery under the influence of various treatment regimens is an urgent task for choosing optimal approaches to curing patients with GERD. The purpose of the study was to evaluate the efficacy and safety of the combination therapy with a proton pump inhibitor (PPI) and a topical mucosal protective agent (MPA) to relieve GERD symptoms and achieve a complete remission of reflux esophagitis faster.

Methods: 60 patients (38 men and 22 women with an average age 41.5 years) with GERD duration of 5 years, took part in an open randomized prospective clinical study. Participants were randomized in a 1:1 ratio to be divided into the main group taking MPA and PPI and a comparison group taking a PPI only. The duration of therapy was 4 weeks. Before the treatment onset and after the end of treatment, the occurrence and severity of GERD symptoms were assessed, an endoscopic examination was performed and biopsy specimens were taken from the edge of the erosive area and the area of unchanged esophageal mucosa. The severity of histological signs of esophagitis, the expression of tight junction proteins and the proliferation marker Ki-67 were assessed.

Results: A more effective relief of GERD symptoms was documented when using combination therapy PPIs and MPAs. A more pronounced reduction in macroscopic changes was found in patients with erosive esophagitis taking PPIs and MPAs. The use of MPAs in addition to PPIs made it possible to achieve the primary and secondary endpoints more often, which suggested a high efficiency of the drug in combination with PPIs in the treatment of erosive esophagitis.

Conclusions: An individualized approach based on the combination therapy of PPIs and MPAs can improve the effectiveness of treatment in achieving clinical, endoscopic and, more importantly, histological remission in a patient with erosive GERD.