Pirfenidone Improves Idiopathic Pulmonary Fibrosis Survival

Diedtra Henderson

January 09, 2019

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 the…cohort, unlike what happens in pharmaceutical trials," the authors write.

George A. Margaritopoulos, MD, PhD, University Hospital of Heraklion, Greece, and colleagues published their findings online 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. 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 prior to 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 3 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 is the team's inability to tease out whether some of 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 [a] 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. The patients were enrolled in sun-splashed southern Greece, so prior to providing pirfenidone, physicians counseled them about sun-protection tactics, including wearing wide-brimmed hats, sunglasses, and using sunscreen with a high sun protection factor, the authors add.

"Several limitations inherent to the design of the study and differences between the two cohorts limit direct comparisons," Gregory P. Cosgrove, MD, chief medical officer of the Pulmonary Fibrosis Foundation, said in a statement. "The findings support prior observations that treatment with the antifibrotic therapy pirfenidone has a durable impact for patients with idiopathic pulmonary fibrosis. With enhanced education, mitigation of possible side effects and continued patient engagement, persistent therapy with antifibrotic therapies may have long-term benefits for patients."

IPF is a chronic, progressive lung disease that causes fibrosis (scar tissue) to accumulate in the lungs, reducing the lungs' ability to reliably deliver oxygen to the bloodstream. The rare disease usually strikes people in their 50s to 70s and is estimated to affect three to nine people per 100,000 in Europe and North America.

Cosgrove reports receiving fees for consulting and advising from Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Global Blood Therapeutics, and Veracyte; serving on a steering committee for Global Blood Therapeutics; and being the chief medical officer for the Pulmonary Fibrosis Foundation. The remaining authors have disclosed no relevant financial relationships.

BMC Pulmonary Medicine. Published online November 23, 2018. Abstract

For more news, join us on  Twitter  and  Facebook


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.