Esbriet’s Efficacy in Severe IPF Seen to Diminish 6-12 Months After Treatment’s Start, Study Shows

Esbriet (pirfenidone) seems to have diminishing therapeutic effect after six months of treatment and possibly no benefit after one year in idiopathic pulmonary fibrosis (IPF) patients with advanced disease, a Greek retrospective study shows.

The study, “Safety and efficacy of pirfenidone in severe Idiopathic Pulmonary Fibrosis: A real-world observational study,” appeared in the journal Pulmonary Pharmacology & Therapeutics.

Esbriet, developed by Genentech, is an anti-fibrotic therapeutic whose efficacy was proven in five randomized multicenter clinical trials with IPF patients of mild-to-moderate disease severity. However, its efficacy in patients with more advanced disease requires further studies.

Researchers at the Sotiria Medical School — a division of the University of Athens — performed a retrospective multicenter study of IPF patients with severe lung function impairment to investigate Esbriet’s safety and efficacy in this particular patient population.

Patients who had been treated with Esbriet before or showed significant comorbidities such as cancer, liver failure or renal failure were excluded from the study.

The team analyzed the results of 34 males and nine females with severe lung function impairment who received Esbriet (2.403 mg/daily) for between six months and one year. Patients’ mean age was 66.3 years, and most were ex-smokers.

The analysis showed that Esbriet administered for six months was associated with a trend for halting functional decline when compared to patients’ lung function in the six months before beginning treatment. These effects appear to then start diminishing.

“However, pirfenidone failed to show any benefit or even halt disease progression after one year of treatment,” the researchers wrote.

Even when researchers analyzed patients’ response according to the duration of Esbriet treatment, after one year the therapy had no effect on disease progression.

But results also showed that Esbriet maintained the safety profile observed in previous large randomized controlled clinical trials. The most common adverse events included gastrointestinal disorders such as nausea and vomiting (34.9 percent), fatigue (23.2 percent) and photosensitivity or rash (18.6 percent). Nine patients had to discontinue treatment due to severe adverse events.

During the study, 21 patients died – 18 patients after 12 months and three patients after six months of Esbriet therapy – due to disease progression or exacerbation.

“Our data suggest an acceptable safety and efficacy profile of pirfenidone treatment in real-life IPF patients with severe lung function impairment. Our preliminary findings indicate a time-limited therapeutic profile of pirfenidone in IPF patients with rapid disease progression,” the researchers concluded, noting that treatment effects “may diminish” after six months of treatment.

“Further prospective studies will help us identify subgroups of patients with different responses to pirfenidone” for more precise treatment approaches, they added.