International treatment guidelines for idiopathic pulmonary fibrosis (IPF) give a conditional recommendation for anti-acid therapy. As some observational studies reported discrepant findings on the effectiveness of anti-acid therapy on mortality in IPF, we reviewed all studies to evaluate whether immortal time bias explains these discrepancies.We searched the Embase and MEDLINE databases up to July 2017 for observational studies assessing the effectiveness of anti-acid therapy on mortality in IPF. Hazard ratios of mortality with anti-acid therapy were pooled across studies using random-effect models, stratified by the presence of immortal time bias.We identified 10 observational studies. Four of the five studies reporting beneficial effects of anti-acid therapy use on mortality were affected by immortal time bias (pooled hazard ratio 0.46; 95% CI 0.30-0.69), while it was unclear whether the fifth was affected. The five studies that avoided immortal time bias reported no effect of anti-acid therapy on mortality (pooled hazard ratio 0.99; 95% CI 0.81-1.22).The apparent beneficial effects of anti-acid therapy on mortality in patients with IPF result from observational studies affected by immortal time bias. Thus, the effectiveness of anti-acid therapy in IPF remains uncertain and needs to be reassessed with more accurate observational study methods and randomised trials.
Background: Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF. Methods: The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for lefttruncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors. Results: The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cutoffs , the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9). Conclusions: EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.
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