Real-world Study Supports Effectiveness, Safety of Esbriet for Treating IPF

A real-world, multi-center study in Poland confirms the effectiveness and safety of two-year treatment with Esbriet (pirfenidone) for people with idiopathic pulmonary fibrosis (IPF).

The study “A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study” was published in the journal BMC Pulmonary Medicine.

Genentech’s Esbriet and Boehringer Ingelheim’s Ofev  (nintedanib) are two anti-fibrotic treatments that have been shown to slow IPF progression and help limit lung function decline.

Esbriet has been approved for IPF treatment in Europe since 2011. Yet, due to lack of reimbursement policies, wide access to the medication for Polish patients was limited. But in 2017 Poland implemented a reimbursement program to promote wider access to the anti-fibrotic therapy.

Data from clinical trials have shown that Esbriet reduces the decline in forced vital capacity (FVC, a measure of lung function) and is associated with a lower mortality rate. Yet, studies often have a short follow-up duration and include a small number of patients.

The PolExPIR study included IPF patients treated with Esbriet from January 2017 until September 2019, as part of the Polish National Health Fund therapeutic program. Patients were registered at 10 pulmonary centers across Poland. The study sought to provide insights about Esbriet outcomes in a real-world setting.

Researchers evaluated patients’ lung function measures using the FVC parameter and diffusing capacity of the lung for carbon monoxide (DLCO or TLCO). They also assessed patients’ exercise capacity and endurance through the six-minute walk test (6MWT).

In total, researchers analyzed data from 307 IPF patients (mean age at diagnosis of 68.8 years; 77% were men) followed for a median of 17 months. More than 68% were ex-smokers and 4% still smoked at start of treatment.

About 85% of patients were diagnosed due to the presence of usual interstitial pneumonia. The median period from first symptoms to IPF diagnosis was 15.5 months.

At the start of the study (baseline), the median FVC predicted of the patient group analyzed was 77.08% and median TLCO of 52.24%. Mean partial arterial oxygen pressure was 69 mmHg (millimeters of mercury) and was  evaluated in 207 patients. The median distance patients walked in the 6MWT was 490 meters, or 535 yards (data from 165 patients).

Results showed that during the first year of treatment, FVC saw a median decline of 20 ml (226 patients) and 120 ml by the second year (61 patients). This corresponded to a median change from baseline of minus 0.68% for the first year and minus 5.42% at the end of the second year.

Moreover, the median TLCO declined by 0.34 millimoles per minute per kilopascal of pressure (mmol/min/kPa) in the first year and 0.57 in the second year, corresponding to a median change from baseline of minus 4.94% at year one and minus 8.18% at year two. In addition, the 6MWT had no changes at the end of the first year and saw a reduction of 31.5 meters (about 34 yards) by the term of the second year.

These results suggested that “over up to 24 months of follow-up, the pulmonary function of patients with IPF receiving pirfenidone remained largely stable,” the researchers wrote.

FVC changes were stable for most patients with only a minority showing marginal (range 4–14%) or significant improvements (0–6%). There also was a small fraction of patients who experienced either a marginal (12–29%) or significant (2–7%) decline in FVC.

Regarding safety, 141 patients stopped treatment not only because of adverse reactions (16.61%), but also due to disease progression (6.51%), by request (5.54%), cancer diagnosis (3.91%), or lung transplant (0.33%).

In total, 24.1% of patients required dose adjustments or temporary treatment interruptions during follow-up, and about 11.4% ended up being treated with a different dose from the recommended full dose.

Most common adverse drug reactions included fatigue (35.83%), reduced appetite (34.2%), weight loss (32.57%), cough (28.66%), nausea (24.43%), dyspepsia (indigestion, 23.13%), skin rash (18.89%), and photosensitivity (reactions to light exposure, 17.59%).

Over the study period, 33 patients (10.75%) died.

“Taken together, the main study findings confirm pirfenidone’s long-term acceptable safety and efficacy profiles and reinforce conclusions from the previous RCTs [randomized clinical trials] and observational studies,” the team concluded.