Esbriet (pirfenidone) can prolong idiopathic pulmonary fibrosis (IPF) patients’ survival, according to a review of clinical trials covering the anti-inflammatory and anti-fibrotic agent.
Researchers also said that Esbriet is safe, but does not help every IPF patient.
The study, “Role of pirfenidone in the management of pulmonary fibrosis,” appeared in the journal Therapeutics and Clinical Risk Management. It was conducted by Keith C. Meyer of the University of Wisconsin Lung Transplant and Advanced Lung Disease Program and Catherine A. Decker of the University of Wisconsin School of Medicine and Public Health.
Pulmonary fibrosis is the most common interstitial lung disease, or ILD, a group of disorders that involve scarring of lung tissue. It can lead to progressive decline in lung function, poor quality of life, and early death.
IPF affects up to one in 200 older people. Patients’ median survival rate is only three to five years after diagnosis.
The disease’s progression can be worsened by comorbidities, or other disorders, including pulmonary hypertension and sleep-disordered breathing. Scientists believe it is triggered by damage to protective epithelial cells in the alveoli, the tiny air sacs at the end of the lungs’ respiratory tree, and the release of cytokines that trigger inflammation. Cytokines are molecules that promote cell to cell communication in immune responses and stimulate the movement of cells toward sites of inflammation, infection and injury.
Previous studies have indicated that IPF fails to respond to immunotherapy. Recent clinical trials have demonstrated that novel anti-fibrotic agents have improved lung function over time, however. Anti-fibrotics ameliorate lung-tissue thickening and scarring.
Esbriet slows IPF patients’ decline in respiratory function and increases their progression-free survival, according to the review. It also reduces mortality, which other anti-fibrotic therapies such as Ofev (nintedanib) are unable to do, researchers said.
Based on these findings, the United States Food and Drug Administration (FDA) approved Esbriet for treating IPF in 2014.
More recently, the ASCEND phase 3 clinical trial (NCT01366209) supported Esbriet’s effectiveness. The study involving 555 patients showed that Esbriet improved respiratory function, progression-free survival, and ability to exercise.
Importantly, a combined analysis of two clinical trials — ASCEND (NCT00287716) and CAPACITY (NCT00287729) — indicated that factors such as patient age, race, smoking status and geographic origin had no impact on Esbriet’s effectiveness.
The clinical trials have also shown that prolonged treatment — that is, beyond six months — continued to reduce the risk of IPF patients’ respiratory decline and death. In addition, pooled data from five clinical studies covering 1,299 patients supported a previous finding that Esbriet is well-tolerated.
Another significant finding was that a combination of Esbriet and the amino acid N-acetylcysteine worsened IPF patients’ respiratory function, compared with Esbriet alone. The discovery came out of the recent PANORAMA phase 2 trial (2012-000564-14).
Although the results on Esbriet are encouraging, the researchers who did the review said doctors should approach its use with caution. That’s because not all IPF patients have better respiratory function and live longer after taking it.
But “individuals with more rapidly declining lung function prior to beginning pirfenidone treatment are more likely to experience benefit,” the researchers wrote.
Side effects of Esbriet include gastrointestinal problems, skin reactions, weight loss, anorexia and fatigue, according to the review. Patients taking it should avoid smoking and drugs that inhibit Esbriet’s metabolism in the liver, the researchers said.
Those taking Esbriet should be carefully monitored, particularly those with severe liver or kidney dysfunction, they said.
The benefits of early treatment with Esbriet, compared with the risks, have yet to be investigated, the researchers said. They also called for studies on the potential benefits of using a combination of Esbriet and Ofev, and on whether Esbriet can help patients with advanced cases of IPF.
“Prior to initiating treatment with pirfenidone, a thorough dialogue with the patient, which includes an educational overview of the benefits, risks, and limitations of therapy, is recommended,” the researchers concluded.