• Tananchai Petnak, Ploypin Lertjitbanjong, Charat Thongprayoon, and Teng Moua.
• Division of Pulmonary and Pulmonary Critical Care Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
• Chest. 2021 Nov 1; 160 (5): 175117631751-1763.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with significant morbidity and mortality. Nintedanib and pirfenidone are two antifibrotic medications currently approved for slowing the rate of lung function decline in IPF, but data on treatment effect on mortality and risk of acute exacerbation (AE) remains limited or unknown.Research QuestionDoes antifibrotic treatment decrease risk of mortality and AE?Study Design And MethodsA comprehensive search of several databases, including Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, was conducted. Studies were included if they were original articles comparing mortality or AE events in IPF patients with and without antifibrotic treatment. Relative risk (RR) with 95%CI was pooled using random-effects meta-analyses with inverse variance method, assessing two primary outcomes of all-cause mortality and AE risk.ResultsA total of 12,956 patients across 26 studies (eight randomized controlled trials and 18 cohort studies) were included in the meta-analysis. Antifibrotic treatment was associated with decreased risk of all-cause mortality with a pooled RR of 0.55 (95% CI, 0.45-0.66) and I2 of 82%. This effect was consistent across additional subgroup analyses, including stratification by study type, risk of bias, duration of follow-up, and antifibrotic subtype. Antifibrotic treatment also reduced the risk of AE, with a pooled RR of 0.63 (95% CI, 0.53-0.76), and I2 of 0%. Effect on AE risk was consistent across subgroup analyses by study type and for nintedanib but not for pirfenidone.InterpretationAntifibrotic treatment appears to reduce the risk of all-cause mortality and AE in IPF. Despite greater heterogeneity with pooled analysis, its effect was robust in subgroup analyses by study type, duration of follow-up, and antifibrotic subtype.Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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