Effectiveness of Proton Pump Inhibitors in Idiopathic Pulmonary Fibrosis: A Population-Based Cohort Study

Abstract

Background: Gastroesophageal reflux disease is a common comorbidity in idiopathic pulmonary fibrosis (IPF) and may contribute to its progression. Anti-acid therapy, such as proton pump inhibitors (PPIs), has been considered as a potential treatment option for IPF. The evidence for this treatment comes from several observational studies affected by time-related bias.

Research question: Is use of PPIs in patients with IPF associated with a reduction in all-cause mortality, respiratory-related mortality, and respiratory-related hospitalization?

Study design and methods: We used the UK Clinical Practice Research Datalink to identify a cohort of patients diagnosed with IPF between 2003 and 2016. The prevalent new-user cohort design was used to match patients initiating PPIs with non-users using time-conditional propensity scores, with follow-up until death or end of observation. Cox models were used to estimate hazard ratios (HR) and 95% CIs of death and of a respiratory-related hospitalization, correcting for informative censoring by inverse probability weighting.

Results: There were 1,852 PPI users who were matched to 1,852 non-users identified among the cohort of patients with IPF, with a median survival of 2.8 years (mortality rate, 26.7 per 100 per year). The HR of all-cause mortality with PPI use was 1.07 (95% CI, 0.94-1.22), relative to non-use. For respiratory-related mortality, the HR was 1.10 (95% CI, 0.94-1.28) and 1.00 (95% CI, 0.86-1.16) for respiratory-related hospitalizations.

Interpretation: PPI use was not associated with lower mortality or hospitalization incidence in this large study conducted among patients with IPF within a real-world setting of clinical practice and designed to avoid the time-related biases affecting previous studies. PPIs may not be as beneficial in treating IPF as suggested by some studies and conditionally recommended in treatment guidelines.

Keywords: idiopathic pulmonary fibrosis; observational study; pharmacoepidemiology; proton pump inhibitors.