Impact of Antifibrotic Therapy on Mortality and Acute Exacerbation in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis

Background: Idiopathic 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 Question: Does antifibrotic treatment decrease risk of mortality and AE? Study Design and Methods: A 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. Results: A 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. Interpretation: Antifibrotic 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.