Efficacy of antifibrotic drugs, nintedanib and pirfenidone, in treatment of progressive pulmonary fibrosis in both idiopathic pulmonary fibrosis (IPF) and non-IPF: a systematic review and meta-analysis

Abstract

Background Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF. Study design and methods A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies. Results 13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was − 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were − 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71. Interpretation Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy. Trial Registration PROSPERO, registration number CRD42021266046.

COVID-19-Associated Lung Fibrosis: Two Pathways and Two Phenotypes, Lung Transplantation, and Antifibrotics

“…The INBUILD study showed a reduction in FVC decline of about 60% compared to placebo. For both antifibrotic drugs, pirfenidone and nintedanib, a meta-analysis showed a reduced decline in the forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF) and also non-IPF patients [39]. As suggested by Wells et al, there may be a common pathway in non-IPF disease with IPF-like disease progression [42].…”

“…IPF is defined as a spontaneously occurring (idiopathic) specific form of chronic fibrosing interstitial pneumonia associated with a pattern of Usual Interstitial Pneumonia (UIP) on imaging or histology [38]. It has been shown that both pirfenidone and nintedanib also show efficacy in non-IPF patients with progressive fibrosis [39]. This was shown both for nintedanib (INBUILD) and for pirfenidone [40,41].…”

Mesenchyme Stem Cell-Derived Conditioned Medium as a Potential Therapeutic Tool in Idiopathic Pulmonary Fibrosis

“…The two approved therapies are the antifibrotic agents pirfenidone and nintedanib. The efficacy of these two therapies is very similar, with several studies showing no significant difference between either drug when comparing the decline of pulmonary function and 2-year mortality rates [ 20 , 21 , 22 ]. Clinical trials have shown these two drugs can decrease the rate of decline of forced vital capacity by 50% over a year of treatment, and 2-year mortality rates after treatment initiation were roughly 36% for pirfenidone-treated patients and 39% for nintedanib-treated patients [ 22 , 23 ].…”

Transitional alveolar epithelial cells and microenvironmental stiffness synergistically drive fibroblast activation in three-dimensional hydrogel lung models

“…Idiopathic pulmonary fibrosis (IPF) is a debilitating interstitial lung disease marked by progressive stiffening of the pulmonary extracellular matrix (ECM), which impairs gas exchange, reduces compliance, and leads to respiratory failure within 3 to 5 years 1 . The only FDA-approved drug treatments for IPF slow disease progression but do not reverse altered lung mechanics and function [2][3][4] . Mechanistic studies of the disease indicate that repeated injury to alveolar epithelial type II (ATII) cells induces differentiation into alveolar epithelial type I (ATI) cells as part of normal re-epithelialization.…”