Antacid Therapy and Disease Progression in Patients with Idiopathic Pulmonary Fibrosis Who Received Pirfenidone

Respiration. 2017;93(6):415-423. doi: 10.1159/000468546. Epub 2017 Apr 12.

Abstract

Background: Gastroesophageal reflux disease is a potential risk factor for idiopathic pulmonary fibrosis (IPF) progression; however, the impact of antacid therapy (AAT) is under debate.

Objective: To evaluate the effect of AAT on IPF progression in pirfenidone-treated patients.

Methods: This post hoc analysis included patients with IPF who received pirfenidone in 3 trials (CAPACITY [PIPF-004/PIPF-006] and ASCEND [PIPF-016]). Pulmonary function, exercise tolerance, survival, hospitalizations, and adverse events (AEs) over 52 weeks were analyzed by baseline AAT use. Disease progression was defined as a decrease in forced vital capacity (FVC) of ≥10%, a decrease in 6-min walking distance of ≥50 m, or death over 1 year.

Results: Of 623 patients, 44% received AAT. No significant differences were found at 52 weeks (AAT versus non-AAT, respectively) in disease progression (24.9 vs. 30.6%; p = 0.12), all-cause mortality rate (2.9 vs. 4.0%; p = 0.47), IPF-related mortality rate (1.1 vs. 2.0%; p = 0.37), all-cause hospitalization rate (16.1 vs. 18.3%; p = 0.48), or mean change in percent FVC (-2.7 vs. -3.1%; p = 0.44). A relative, but not absolute, FVC decline of ≥10% favored AAT (15 vs. 22%; p = 0.03). Severe gastrointestinal AEs (3.7 vs. 0.9%; p = 0.015) and severe pulmonary infections (3.7 vs. 1.1%; p = 0.035) were more frequent with AAT.

Conclusions: AAT and pirfenidone had outcomes comparable to those of pirfenidone alone in patients with IPF, underscoring the need for prospective trials to elucidate the role of AAT with or without antifibrotic drugs as a treatment for IPF.

Keywords: Antacid therapy; Gastroesophageal reflux disease; Idiopathic pulmonary fibrosis; Pirfenidone; Progression-free survival.

MeSH terms

  • Aged
  • Antacids / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cause of Death
  • Disease Progression
  • Exercise Tolerance / physiology
  • Female
  • Gastroesophageal Reflux / complications
  • Gastroesophageal Reflux / drug therapy*
  • Histamine H2 Antagonists / therapeutic use*
  • Hospitalization / statistics & numerical data
  • Humans
  • Idiopathic Pulmonary Fibrosis / complications
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / mortality
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Male
  • Middle Aged
  • Mortality
  • Proton Pump Inhibitors / therapeutic use*
  • Pyridones / therapeutic use*
  • Respiratory Function Tests
  • Survival Rate
  • Vital Capacity
  • Walk Test

Substances

  • Antacids
  • Anti-Inflammatory Agents, Non-Steroidal
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors
  • Pyridones
  • pirfenidone