Immediate discontinuation versus gradual tapering of proton pump inhibitors in long-term users: a randomized controlled trial.

BACKGROUND

Proton pump inhibitors (PPIs) are often continued after symptoms have improved, despite no clear indications for maintenance therapy. Although unnecessary long-term PPI use should be avoided, concerns about symptom rebound after discontinuation frequently discourage withdrawal; evidence comparing discontinuation strategies remains insufficient.

METHODS

We conducted a multicenter, randomized, parallel-group trial comparing immediate discontinuation and gradual tapering of PPIs, including PCABs, in clinically stable outpatients with gastroesophageal reflux disease receiving long-term PPI therapy. Participants were randomized 1:1 to abrupt discontinuation or dose reduction to half for 2 weeks followed by discontinuation. Rescue PPI use was permitted as needed. Successful discontinuation was defined as ≤ 8 days of rescue PPI use during each 28-day assessment window. The primary outcome was successful discontinuation at 24 weeks, and the secondary outcome was successful discontinuation at 48 weeks. Analyses were performed primarily in the intention-to-treat population.

RESULTS

Sixty-three participants were randomized. At 24 weeks, successful discontinuation was achieved in 74.2% of the immediate discontinuation group and 75.0% of the gradual taper group (risk difference: - 0.008, 95% CI: - 0.231 to 0.215). Results were similar at 48 weeks and in per-protocol analyses. No protocol-specified adverse events were observed. On exploratory analyses, older age and lower baseline regurgitation score were associated with successful discontinuation. Rescue medication use occurred early after discontinuation but did not preclude long-term success.

CONCLUSIONS

Immediate discontinuation and gradual tapering resulted in comparable rates of successful PPI withdrawal in clinically stable patients. Counseling regarding transient symptoms and on-demand rescue therapy may facilitate successful discontinuation regardless of strategy.