Treating patients who have idiopathic pulmonary fibrosis (IPF) with pirfenidone (Esbriet, Genentech) increases their 3-year survival rates and confers a 30% survival benefit compared with patients who have not been treated with antifibrotic agents, according to a retrospective observational intention-to-treat study.

"The effect of pirfenidone on survival is remarkable if [one] takes into account that patients with comorbidities and severe disease have been included in cohort, unlike what happens in pharmaceutical trials," the authors write. George A. Margaritopoulos, MD, Ph.D., University Hospital of Heraklion, Greece, and colleagues published their findings online on November 23 in BMC Pulmonary Medicine.

After European and US drug regulators approved pirfenidone to treat IPF in 2011 and 2014, respectively, it became unethical to withhold the antifibrotic medicine from patients in the control group of randomized controlled clinical trials.

Efficacy of Pirfenidone

For this reason, the researchers analyzed longitudinal real-world data to gauge the efficacy of pirfenidone in patients newly diagnosed with IPF (the UHH cohort) and compared their survival rates with other patients with IPF who had been studied before pirfenidone's approval. The team enrolled 82 patients (mean age, 74.9 years) with IPF who had been referred to an interstitial lung disease outpatient clinic from July 2011 to December 2016.

Nearly 65% were current or former smokers whose smoking history was 43.5 pack years. Patients' mean forced vital capacity (FVC) was 81.5% and the most common comorbidities included systemic hypertension (64%), gastroesophageal reflux disease (47%) and ischemic heart disease (30%).

These patients were treatment naïve and took 2403 mg pirfenidone per day for at least three months.The final analysis compared survival data from 75 patients in the UHH cohort to survival data from 136 patients with IPF from a tertiary referral center in the United Kingdom. In the unadjusted analysis, survival in the UHH cohort was better than in the patients studied before the approval of pirfenidone (hazard ratio, 0.32; 95% confidence interval, 0.19 – 0.53, P < .0001).

"After adjustment for FVC, age, and gender the result did not change," the authors write. Among the study, limitations are the team's inability to tease out whether some of the pirfenidone's observed benefit is a result of the adverse effects of immunosuppressive treatment that was once the standard of care for patients with IPF.

The team acknowledges "the combination of low dose of prednisolone with azathioprine and N-acetyl-cysteine has been proved not efficacious and deleterious in IPF."Thirty of 75 patients in the UHH cohort (40%) reported gastrointestinal discomfort, and three discontinued pirfenidone treatment after experiencing gastrointestinal adverse events. Seventeen patients (22.6%) in that cohort experienced photosensitivity, and nine discontinued treatment as a result.