Antifibrotic Pirfenidone in Patients With Progressive Pulmonary Fibrosis

Is the antifibrotic pirfenidone an effective and safe therapy for individuals with progressive pulmonary fibrosis?

In patients with progressive pulmonary fibrosis (PPF), treatment with the antifibrotic agent pirfenidone is associated with a statistically significant decrease in disease progression and protection in lung function, with the main adverse events (AEs) reported being gastrointestinal (GI) discomfort and photosensitivity. A systematic review and meta-analysis on the subject were conducted, with the results published in Annals of the American Thoracic Society.1

In an effort to inform a clinical practice guideline under development by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax, researchers sought to evaluate the existing literature on interstitial lung disease (ILD) to determine whether patients with PPF should be treated with pirfenidone. The current literature search was conducted through December 2020. Mortality, disease progression, lung function, and AE data were obtained, with meta-analyses conducted whenever possible. To evaluate the quality of the evidence, the investigators used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group approach.

There were 2 studies that fulfilled inclusion criteria. The primary reason for the exclusion of studies was a lack of documented progression of disease as an a priori criterion within the studies for inclusion. The first study included in the analysis was a phase 2, randomized, controlled trial that was published in 2020.2 This study followed 253 patients across 14 countries over a 24-week period. The second study was the randomized controlled RELIEF trial, which was published in 2021.3 This study evaluated 127 patients across 17 sites in Germany over 48 weeks.

Meta-analyses revealed changes in percent predicted forced vital capacity (FVC%; mean difference [MD], 2.3%; 95% CI, 0.5-4.1%), FVC in mL (MD, 100.0 mL; 95% CI, 98.1-101.9 mL) and 6-minute walking distance (6MWD) in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) — all in favor of pirfenidone over placebo.

Change in diffusing capacity of the lung for carbon monoxide (DLCO) in mmol/kPa/min (MD, 0.40 mmol/kPa/min; 95% CI, 0.10-0.70 mmol/kPa/min) and risk for DLCO declining >15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) favored pirfenidone over placebo as well.

The risks for GI discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone than with placebo. Depending on the outcome, the quality of the evidence was low or very low GRADE.

The investigators concluded that very low certainty exists regarding the estimated effects that were reported, because of limitations in the available evidence. Given the limited number of studies on this topic currently available in the literature, additional research on pirfenidone is warranted, in order to clarify whether the trends observed in this systematic review persist in more studies with larger sample sizes.


1. Ghazipura M, Mammen MJ, Bissell BD, et al. Pirfenidone in progressive pulmonary fibrosis: a systematic review and meta-analysis. Ann Am Thorac Soc. Published online May 2, 2022. doi:10.1513/AnnalsATS.202103-342OC

2. Maher TM, Corte TJ, Fischer A, et al. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2020;8(2):147-157. doi:10.1016/S2213-2600(19)30341-8

3. Behr J, Prasse A, Kreuter M, et al. Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med. 2021;9(5):476-486. doi:10.1016/S2213-2600(20)30554-3