Pirfenidone Safety, Efficacy in Progressive Fibrotic ILDs Besides IPF

Interstitial lung disease, CT scan
In patients with fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis, adding pirfenidone to treatment may attenuate disease progression.

In patients with fibrotic interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF), adding pirfenidone to treatment may attenuate disease progression, according to the results of a multicenter, double-blind, phase 2b trial (EU Clinical Trials Register Identifier: EudraCT 2014-000861-32) published in the journal Lancet Respiratory Medicine.

Pirfenidone slows disease progression in patients with IPF; however, there are few treatment options for progressive fibrotic ILDs other than IPF. Therefore, researchers in Germany assessed the efficacy and safety of pirfenidone in patients with non-IPF progressive fibrotic ILDs: collagen or vascular diseases, fibrotic nonspecific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis.

Patients were randomly assigned to either oral pirfenidone (n=64) or matched placebo (n=63) added to their ongoing medication. The study was prematurely terminated on the basis of an interim analysis for futility triggered by slow recruitment. After 48 weeks, rank analysis of covariance (ANCOVA) with diagnostic group included as a factor showed a significantly lower decline in forced vital capacity (FVC) percent predicted in the pirfenidone group compared with placebo (P=.043).

The median difference between pirfenidone and placebo groups for the primary endpoint was 1.69 FVC percent predicted. In a linear mixed-model repeated measures slope analysis of FVC percent predicted, the estimated difference between treatment and placebo groups from baseline to week 48 was 3.53 FVC percent predicted with imputation of deaths as prespecified, or 2.79 FVC percent predicted without imputation.

One death (nonrespiratory) occurred in the pirfenidone group and 5 deaths (3 of which were respiratory) occurred in the placebo group (8%). The most frequent serious adverse events in both groups were infections and infestations (5 in the pirfenidone group, 10 in the placebo group).

“In summary, we showed that treatment of patients with progressive fibrotic ILDs other than IPF with pirfenidone is safe, with the side effect profile being similar to that reported in IPF trials,” the authors stated. “However, because of the premature termination of our study and the resulting limitations with regard to patient numbers and missing values, these results should be interpreted with caution.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Behr J, Prasse A, Kreuter M, et al; on behalf of the RELIEF investigators. 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. Published online March 30, 2021. doi:10.1016/S2213-2600(2)30554-3