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Randomized Controlled Trial
. 2013 Jul;1(5):369-76.
doi: 10.1016/S2213-2600(13)70105-X. Epub 2013 Jun 14.

Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials

Joyce S Lee  1 , Harold R Collard  1 , Kevin J Anstrom  2 , Fernando J Martinez  3 , Imre Noth  4 , Rhonda S Roberts  2 , Eric Yow  2 , Ganesh Raghu  5 ; IPFnet Investigators
Affiliations
Randomized Controlled Trial

Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials

Joyce S Lee et al. Lancet Respir Med. 2013 Jul.

Abstract

Background: Abnormal acid gastro-oesophageal reflux is common in patients with idiopathic pulmonary fibrosis (IPF) and is considered a risk factor for development of IPF. Retrospective studies have shown improved outcomes in patients given anti-acid treatment. The aim of this study was to investigate the association between anti-acid treatment and disease progression in IPF.

Methods: In an analysis of data from three randomised controlled trials, we identified patients with IPF assigned to receive placebo. Case report forms had been designed to prospectively obtain data about diagnosis and treatment of abnormal acid gastro-oesophageal reflux in each trial. The primary outcome was estimated change in forced vital capacity (FVC) at 30 weeks (mean follow-up) in patients who were and were not using a proton-pump inhibitor or histamine-receptor-2 (H2) blocker.

Findings: Of the 242 patients randomly assigned to the placebo groups of the three trials, 124 (51%) were taking a proton-pump inhibitor or H2 blocker at enrolment. After adjustment for sex, baseline FVC as a percentage of predicted, and baseline diffusing capacity of the lung for carbon monoxide as a percentage of predicted, patients taking anti-acid treatment at baseline had a smaller decrease in FVC at 30 weeks (-0·06 L, 95% CI -0·11 to -0·01) than did those not taking anti-acid treatment (-0·12 L, -0·17 to -0·08; difference 0·07 L, 95% CI 0-0·14; p=0·05).

Interpretation: Anti-acid treatment could be beneficial in patients with IPF, and abnormal acid gastro-oesophageal reflux seems to contribute to disease progression. Controlled clinical trials of anti-acid treatments are now needed.

Funding: National Institutes of Health.

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Figures

Figure 1
Figure 1
Flow diagram of the three parent clinical trials (STEP-IPF, ACE-IPF, and PANTHER-IPF) and how patients were identified and categorized in this study.
Figure 2
Figure 2
Repeated measures estimate of change in forced vital capacity (liters) comparing those taking a PPI/H2B (blue line is point estimate and shaded blue region is the 95% confidence interval) and those not taking PPI/H2B (red line is point estimate and shaded red region is 95% confidence interval). This is adjusted for sex, baseline FVC %predicted, and baseline DLCO %predicted.
Figure 3
Figure 3
Kaplan Meier survival curves for (A) acute exacerbation, (B) all-cause hospitalization, (C) all-cause mortality, and (D) combined endpoint of acute exacerbation, all-cause hospitalization, and all-cause mortality. The blue line represents those taking PPI/H2B and the red line represents those not taking PPI/H2B.
Figure 3
Figure 3
Kaplan Meier survival curves for (A) acute exacerbation, (B) all-cause hospitalization, (C) all-cause mortality, and (D) combined endpoint of acute exacerbation, all-cause hospitalization, and all-cause mortality. The blue line represents those taking PPI/H2B and the red line represents those not taking PPI/H2B.
Figure 3
Figure 3
Kaplan Meier survival curves for (A) acute exacerbation, (B) all-cause hospitalization, (C) all-cause mortality, and (D) combined endpoint of acute exacerbation, all-cause hospitalization, and all-cause mortality. The blue line represents those taking PPI/H2B and the red line represents those not taking PPI/H2B.
Figure 3
Figure 3
Kaplan Meier survival curves for (A) acute exacerbation, (B) all-cause hospitalization, (C) all-cause mortality, and (D) combined endpoint of acute exacerbation, all-cause hospitalization, and all-cause mortality. The blue line represents those taking PPI/H2B and the red line represents those not taking PPI/H2B.
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References

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