Impact of Antifibrotic Therapy on Mortality and Acute Exacerbation in Idiopathic Pulmonary Fibrosis
Abstract
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 information 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% confident interval (CI) was pooled using random-effects meta-analyses with inverse variance method, assessing two primary outcomes of all-cause mortality and acute exacerbation (AE) risk. RESULTS A total of 12,956 patients across 26 studies (8 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 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.
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A systematic review observed that pirfenidone does not improve the risk of acute exacerbations.
“However, a systematic review, observed that pirfenidone does not improve the risk of acute exacerbations, which have a significant impact on prognosis (Petnak et al., 2021).”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Petnak et al., 2021
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- Authors
- Petnak, T., Lertjitbanjong, P., Thongprayoon, C., & Moua, T.
- Affiliations
- Mayo Clinic (US)
- University of Tennessee Health Science Center (US)
- Corresponding author
- Moua, Teng
- Venue
- Chest
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 160
- Issue
- 5
- Pages
- 1751-1763
- ISSN
- 0012-3692 (ISSN-L)
- OpenAlex
- W3177207363
- Semantic Scholar
- 3efb7c34d6f282c63611eafc8ce1165a14af6bb6
- Cited by
- 220
- References
- 49
- Citations by year
- 2026: 33 · 2025: 41 · 2024: 56 · 2023: 49 · 2022: 31 · 2021: 10
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CHEST Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- idiopathic pulmonary fibrosis, antifibrotic therapy, nintedanib, pirfenidone, all-cause mortality, acute exacerbation, interstitial lung disease, lung function decline
- MeSH terms
- Symptom Flare Up, Antifibrotic Agents, Humans, Indoles, Mortality, Pyridones, Treatment Outcome, Idiopathic Pulmonary Fibrosis
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