IPF is a fatal disorder with no proven treatment. Studies have linked GER with reduced gas transfer (Schachter ATS 2001) and showed an increased prevalence of GER in IPF (Tobin AJRCCM 1998). Anti-GER therapy has been recommended in IPF (Kairalla ATS 2003). We sought to examine the frequency of chronic anti-GER use in IPF patients and its relationship to outcome.
We retrospectively analyzed data from a randomized trial evaluating interferon gamma-1b (IFN-gamma 1b) in IPF patients (Raghu NEJM 2004). Chronic anti-GER use was defined as >= 6 months non-prn use of any antacid, sucralfate, H2 blocker, or proton pump inhibitor at study entry; non-users had < 6 months of use or none. Cox proportional hazards regression was used to examine the relationship between chronic anti-GER use and death, disease progression (defined as >= 10% FVC decrease), and hospitalization, while controlling for age, baseline FVC, and use of IFN-gamma 1b.
85 patients used chronic anti-GER medications, in varying doses; 177 patients were non-users. Median follow-up was ∼72 weeks. Rates of death, disease progression, and hospitalization were not significantly different in anti-GER users than non-users. Multivariate analyses found no association between anti-GER use and either death or disease progression. However, anti-GER use was an independent predictor of hospitalization (hazard ratio (HR) 1.9; p = 0.02) and respiratory hospitalization (HR 2.2; p = 0.02). No interaction of anti-GER therapy with use of IFN-gamma 1b was found.
A substantial proportion (32%) of IPF patients received anti-GER treatments chronically. Although no effect on mortality or disease progression was evident, there was an increased risk of hospitalization and respiratory hospitalization in chronic anti-GER users. Since this study was not designed to assess anti-GER efficacy in IPF patients, cause and effect cannot be determined.
Rigorous controlled trials with 24-hour pH esophageal monitoring and evaluation for aspiration are necessary to definitively determine the effect of reducing gastric acid and anti-GER therapy on outcome of IPF.
G. Raghu, Funding provided by InterMune, Inc.