A39-13 Association of Histamine-2 Receptor Antagonist Use With Clinical Outcomes in Patients With Idiopathic Pulmonary Fibrosis: A Propensity-Matched Cohort Study

Abstract Rationale Gastroesophageal reflux disease (GERD) is reported to be more prevalent in patients with idiopathic pulmonary fibrosis (IPF) than in patients without IPF. GERD and micro-aspiration have been implicated in both the pathogenesis and progression of IPF. Current American Thoracic Society (ATS) guidelines note insufficient evidence of routine histamine-2 receptor antagonist (H2RA) therapy in IPF. We investigate the clinical implications of H2RA use in IPF. Methods We conducted a retrospective cohort study using the TriNetX database, a research database which provides de-identified electronic health records across multiple healthcare organizations. Adult patients with IPF exposed to an H2RA within 3 months before or up to 1 year after IPF diagnosis (H2RA users, n = 8,575) were compared with non-users (n = 31,763), from 2015 to 2024. Propensity-score matching by age, sex, race/ethnicity, body mass index (BMI), diffusing capacity of the lungs for carbon monoxide (DLCO), smoking status, comorbidities, and antifibrotic use, was performed, yielding 8,007 patients per group. Cox proportional hazard models were used to assess the association between H2RA use and clinical outcomes of all-cause mortality, emergency department (ED) visits, inpatient admissions, intensive care unit (ICU) admissions, gastrointestinal (GI) bleeding, influenza and pneumonia, acute respiratory distress syndrome (ARDS), and mechanical ventilation. Results Compared with matched non-users Table 1, H2RA users had a significantly higher associated risk of all-cause mortality (hazard ratio HR 1.18, 95% confidence interval CI 1.11-1.27), ED visits (HR 1.18, 95% CI 1.10-1.26), inpatient admissions (HR 1.50, 95% CI 1.42-1.58), ICU admissions (HR 1.84, 95% CI 1.69-2.01), GI bleeding (HR 1.41, 95% CI 1.21-1.65), influenza and pneumonia (HR 1.34, 95% CI 1.25-1.43), ARDS (HR 1.99, 95% CI 1.55-2.56), and mechanical ventilation (HR 1.84, 95% CI 1.52-2.23) (all p 0.001). Conclusions In our propensity-matched analysis, we found that H2RA use in IPF patients was associated with an increased risk of multiple adverse clinical outcomes, including all-cause mortality, ED visits, hospital and ICU admissions, GI bleeding, infectious complications, ARDS, and mechanical ventilation. We agree with current ATS guidelines reporting insufficient evidence to recommend routine use of H2RAs in IPF. In view of conflicting observational data and the lack of robust randomized controlled trials, future research is warranted to clarify the risks and benefits of H2RAs in IPF management. This abstract is funded by: None