Patients older than 75 with idiopathic pulmonary fibrosis (IPF) are at higher risk of discontinuing treatment with Esbriet (pirfenidone) due to adverse reactions, namely anorexia, according to a retrospective analysis made in Japan.
The study, “Differences in tolerability of pirfenidone between elderly and younger patients with idiopathic pulmonary fibrosis,” was published in the journal Drug Design, Development and Therapy.
Esbriet, developed by Genentech, is an approved anti-fibrotic therapy to manage IPF symptoms, and slow disease progression, as supported by data from the Phase 3 ASCEND trial (NCT01366209), and the CAPACITY 1 (NCT00287729) and CAPACITY 2 (NCT00287716) trials. Patients older than 80 were excluded from these trials.
The trials showed that Esbriet reduced IPF patients’ decline in lung function and physical capacity, the number of respiratory-related hospitalizations, and the risk of death, compared with a placebo. The treatment was found to be generally well-tolerated.
In the real world, certain patients, especially the elderly, occasionally need to stop the treatment due to adverse reactions.
“Post-marketing surveillance in Japan revealed that 24.3% of patients discontinued PFD [Esbriet] therapy because of adverse drug reactions,” the researchers wrote.
To assess the potential age-related differences in adverse reactions to Esbriet, and to evaluate whether age influences the safety and tolerability of the IPF therapy, researchers conducted a retrospective analysis of 120 IPF patients treated with Esbriet, between May 2009 and April 2017, at the Chiba University Hospital in Japan.
Participants were divided into two groups according to their age: a group with patients who were 75 or older (elderly group of 31 patients), and another with patients younger than 75 (younger group of 89 patients). The patients’ clinical and laboratory data were reviewed.
Administration of Esbriet followed Japanese guidelines, starting at 600 mg/day for the first two weeks, increasing to 1,200 mg/day, and, if possible, further increased to 1,800 mg/day.
An experienced doctor monitored the treatment, and identified any adverse reactions to the therapy, and decided when the treatment should be reduced or stopped. The team assessed the patients’ tolerability to Esbriet after six and 12 months.
The results showed that after one year of treatment, significantly fewer patients in the elderly group were receiving a higher dose of Esbriet (more than 1,200 mg/day) when compared with patients in the younger group — 35% (11 patients) in the elderly group vs 64% (57 patients) in the younger group.
Adverse reactions to Esbriet were the most common cause of discontinuation in both groups. The discontinuation rates due to all adverse reactions were similar between the two groups after six months (32% in the elderly group vs 20% in the younger group) and at one year (39% vs 24%, respectively).
Clinicians also detected no differences in discontinuation rates between the groups due to disease progression or acute exacerbations, all detected in less than 6% of the participants.
Other reasons for discontinuation were factors not directly related to IPF (including lung cancer, pneumonia, and stroke); the discontinuation rates due to these factors were not significantly different between the two groups.
Anorexia was the most common adverse reaction to Esbriet in both groups, and was significantly higher in the elderly patient group (65%) compared to the younger group (36%).
Other gastrointestinal disorders, including indigestion, gastroesophageal reflux syndrome, nausea, and constipation, were also significantly more prevalent at 77% among the elderly IPF patients vs 45% among the younger patients. This led to a higher discontinuation rate of 35% in the elderly group — more than two times higher — than the 15% discontinuation rate of the younger group.
Age and body surface area were also found to be the strongest factors associated with the incidence of gastrointestinal disorders.
Overall, “compared with younger patients, elderly patients with IPF had a higher incidence of gastrointestinal disorders, along with an increased discontinuation rate of PFD [pirfenidone, the active agent of Esbriet]. More careful management of gastrointestinal disorders may be required to ensure continuation of PFD in elderly patients,” the team concluded.