Changes of Gastric Histology in Patients With Erosive Esophagitis
Changes of Gastric Histology in Patients With Erosive Esophagitis
Background Changes in gastric histology associated with long-term maintenance therapy with lansoprazole for erosive oesophagitis have not been well described.
Aim To evaluate the effect on gastric histology of long-term dose-titrated lansoprazole administered as maintenance therapy for up to 82 months in patients with erosive oesophagitis.
Methods Sequential gastric biopsy specimens were obtained for evaluation of histological changes and Helicobacter pylori infection status.
Results Active and chronic inflammation improved from baseline to final visit in a majority of patients receiving long-term therapy with lansoprazole, irrespective of baseline H. pylori infection status. Reductions in active inflammation in the gastric body and antrum were seen in 53% (17/32) and 67% (20/30) of H. pylori-positive patients, respectively, and in 88% (7/8) and 86% (12/14) of H. pylori-negative patients, respectively. Reductions in chronic inflammation in the gastric body and antrum were seen in 38% (12/32) and 47% (15/32) of H. pylori-positive patients, respectively, and in 58% (70/121) and 57% (68/120) of H. pylori-negative patients, respectively. No clinically meaningful increases in hyperplasia, dysplasia, neoplasia, intestinal metaplasia or atrophy were observed during the follow-up period.
Conclusions Lansoprazole administered as maintenance therapy for up to 6 years in patients with erosive oesophagitis demonstrated gastric mucosal safety and was well tolerated.
Symptoms of gastro-oesophageal reflux disease (GERD) have been reported to occur monthly in almost 50% of adults in the United States and up to 20% of adults report weekly symptoms. Complications of GERD include erosive oesophagitis (EO), Barrett's oesophagus and adenocarcinoma of the oesophagus.
Although short-term treatment with a proton pump inhibitor (PPI) is highly effective in healing EO in a majority of patients, the probability of recurrence is high. Thus, following healing of EO, long-term therapy is usually necessary to maintain disease remission. PPI therapy, as opposed to therapy with histamine-2 receptor antagonists, has been shown to be the preferred long-term management strategy for EO, because of the superior efficacy profile of these agents. Lansoprazole is a well-established PPI and its efficacy, safety and tolerability in preventing relapse in patients with EO are supported by an extensive body of literature.
The long-term clinical efficacy and safety of lansoprazole 15 mg QD as maintenance therapy for EO have been demonstrated in a Phase III, randomized, multicentre study in which patients received open-label lansoprazole for up to 82 months. However, the histological changes associated with long-term lansoprazole therapy have not been well described. Thus, the aim of this study was to evaluate the long-term histological safety of treatment with lansoprazole. To this end, longitudinal gastric biopsy specimens were obtained from patients throughout the Phase III study for the evaluation of changes in active (acute) and chronic inflammation, endocrine cells, intestinal metaplasia, atrophy and Helicobacter pylori infection status. This report summarizes these findings.
Abstract and Introduction
Abstract
Background Changes in gastric histology associated with long-term maintenance therapy with lansoprazole for erosive oesophagitis have not been well described.
Aim To evaluate the effect on gastric histology of long-term dose-titrated lansoprazole administered as maintenance therapy for up to 82 months in patients with erosive oesophagitis.
Methods Sequential gastric biopsy specimens were obtained for evaluation of histological changes and Helicobacter pylori infection status.
Results Active and chronic inflammation improved from baseline to final visit in a majority of patients receiving long-term therapy with lansoprazole, irrespective of baseline H. pylori infection status. Reductions in active inflammation in the gastric body and antrum were seen in 53% (17/32) and 67% (20/30) of H. pylori-positive patients, respectively, and in 88% (7/8) and 86% (12/14) of H. pylori-negative patients, respectively. Reductions in chronic inflammation in the gastric body and antrum were seen in 38% (12/32) and 47% (15/32) of H. pylori-positive patients, respectively, and in 58% (70/121) and 57% (68/120) of H. pylori-negative patients, respectively. No clinically meaningful increases in hyperplasia, dysplasia, neoplasia, intestinal metaplasia or atrophy were observed during the follow-up period.
Conclusions Lansoprazole administered as maintenance therapy for up to 6 years in patients with erosive oesophagitis demonstrated gastric mucosal safety and was well tolerated.
Introduction
Symptoms of gastro-oesophageal reflux disease (GERD) have been reported to occur monthly in almost 50% of adults in the United States and up to 20% of adults report weekly symptoms. Complications of GERD include erosive oesophagitis (EO), Barrett's oesophagus and adenocarcinoma of the oesophagus.
Although short-term treatment with a proton pump inhibitor (PPI) is highly effective in healing EO in a majority of patients, the probability of recurrence is high. Thus, following healing of EO, long-term therapy is usually necessary to maintain disease remission. PPI therapy, as opposed to therapy with histamine-2 receptor antagonists, has been shown to be the preferred long-term management strategy for EO, because of the superior efficacy profile of these agents. Lansoprazole is a well-established PPI and its efficacy, safety and tolerability in preventing relapse in patients with EO are supported by an extensive body of literature.
The long-term clinical efficacy and safety of lansoprazole 15 mg QD as maintenance therapy for EO have been demonstrated in a Phase III, randomized, multicentre study in which patients received open-label lansoprazole for up to 82 months. However, the histological changes associated with long-term lansoprazole therapy have not been well described. Thus, the aim of this study was to evaluate the long-term histological safety of treatment with lansoprazole. To this end, longitudinal gastric biopsy specimens were obtained from patients throughout the Phase III study for the evaluation of changes in active (acute) and chronic inflammation, endocrine cells, intestinal metaplasia, atrophy and Helicobacter pylori infection status. This report summarizes these findings.