Withdrawing PPI therapy after healing esophagitis does not worsen symptoms or cause persistent hypergastrinemia: analysis of dexlansoprazole MR clinical trial data

Abstract

Objectives: Withdrawal of proton pump inhibitors (PPIs) may induce symptoms in healthy volunteers, suggesting that discontinuing PPI therapy induces acid-peptic disease. Similar assessments in patients with documented acid-related disorders are lacking.

Methods: We performed a retrospective analysis of data from 287 Helicobacter pylori-negative erosive esophagitis (EE) patients healed after 4 or 8 weeks of therapy with dexlansoprazole modified release (MR) or lansoprazole, and then randomized to placebo in 6-month maintenance trials. We compared serum gastrin levels and 24-h heartburn severity before enrollment in the healing trials (baseline) and after receiving placebo in the 6-month maintenance trials.

Results: Mean gastrin values at maintenance months 1 and 3 were essentially unchanged (median changes, 1.0 and -1.0 pg/ml), showing that gastrin normalized within 1 month of discontinuing PPIs and remained flat. Mean heartburn severity at maintenance month 1 was <1 on a 5-point scale (1=mild) and significantly lower than at baseline (median decrease, 0.41 points; P≤0.001). Heartburn severity in patients healed at week 4 or 8 with either PPI was generally similar, suggesting that neither longer exposure nor more potent therapy was associated with rebound. In those with month 2 data, mean heartburn severity at months 1 and 2 was significantly lower than baseline (median decrease, 0.54 and 0.58 points; both P<0.001), indicating an ongoing symptom response for 2 months after PPI withdrawal.

Conclusions: In H. pylori-negative EE patients, there was no indication of recurring heartburn symptom worsening beyond baseline levels within 2 months of discontinuing 4-8 weeks of PPI therapy.

Figure 1

Mean serum gastrin levels. EE, erosive esophagitis; PPI, proton pump inhibitor. Error bars represent the s.d.

Figure 2

Median change from baseline in mean 24-h heartburn symptom severity in all placebo-treated patients with data for baseline and weeks 1–4 of the maintenance studies. CFB, change from baseline. P<0.001 for comparison of change from baseline with no change for each week; Wilcoxon signed-rank test.

Figure 3

Heartburn severity during follow-up. Mean 24-h heartburn severity (median) in all placebo-treated patients with baseline and month 1 data shown by (a) previous PPI usage, (b) healing therapy, and (c) duration of healing therapy. EE, erosive esophagitis; PPI, proton pump inhibitor. Mean severity is calculated for each patient based on a 5-point scale: 0=none, 1=mild, 2=moderate, 3=severe, and 4=very severe.