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.
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