A retrospective real-world study found that the benefits of Esbriet (pirfenidone) in people with advanced idiopathic pulmonary fibrosis (IPF) appeared to diminish after six months of treatment, although side effects were similar to those reported in previous clinical trials.
These results were reported in “Safety and efficacy of pirfenidone in severe Idiopathic Pulmonary Fibrosis: A real-world observational study,” published in the journal Pulmonary Pharmacology and Therapeutics.
IPF is a progressive and debilitating disease of unknown cause that is characterized by thickening and scarring (fibrosis) of lung tissue, which makes breathing difficult and decreases the amount of oxygen the lungs can supply to the major organs.
Its treatment was largely limited to supportive care and lung transplants until Esbriet (pirfenidone; marketed by Genentech) along with Ofev (nintedanib; by Boehringer Ingelheim) were approved in 2014.
Esbriet has been shown to slow disease progression in IPF as measured by a decline in forced vital capacity (FVC), or the amount of air a person can forcibly exhale after taking the deepest breath possible.
IPF patients with severe lung function impairment can represent a significant portion of people in a real-life clinical setting, although they are usually not included in Phase 3 trials, the study noted. Researchers for this reason wanted to assess Esbriet’s safety and efficiency in advanced IPF patients to help clinicians in treatment decisions.
The team reviewed medical records of 43 patients with severe IPF who received 2,403 mg of Esbriet a day for one year.
Esbriet use in these patients was found to be associated with a trend toward functional improvement at six months post-treatment initiation, but the therapeutic benefits appeared to diminish six to 12 months after treatment start.
The team noted that the rapid functional deterioration observed during that period was consistent with a large proportion of rapidly progressing patients. These patients, identified based on a 5% decline in FVC after three months of treatment, are known to respond poorly to Esbriet.
The most common adverse events were gastrointestinal disorders (34.9%), fatigue (23.2%) and photosensitivity (18.6%), and they were mild to moderate in severity. These events were consistent with the drug’s safety profile previously reported in three large randomized controlled clinical trials: Phase 3 ASCEND trial (NCT01366209, 52 weeks) and the CAPACITY trials (NCT00287716 and NCT00287729, 72 weeks).
Adverse events experienced by those with severe IPF led to treatment discontinuation in 20.9% of the cases, which was slightly higher than those reported in the ASCEND (14.4%) and CAPACITY (15%) trials. Those studies included patients with mild-to-moderate disease severity.
According to the researchers, the study “adds meaningful knowledge on the safety profile and therapeutic effects of pirfenidone on an underestimated majority of IPF patients.”
“Our preliminary findings indicate a time-limited therapeutic profile of pirfenidone in IPF patients with rapid disease progression. Further prospective studies will help us identify subgroups of patients with different responses to pirfenidone and thus apply precision medicine therapeutic approaches,” the team concluded.