There are only 2 antifibrotics currently available to treat patients with idiopathic pulmonary fibrosis (IPF), a progressive, deadly lung disease that is associated with a median survival time from diagnosis of 2 to 5 years: pirfenidone (Esbriet) and nintedanib.
Although clinical trials provide important safety and efficacy data associated with these treatments, restrictive inclusion and exclusion criteria can make it difficult to apply results to real-world populations of patients with the disease.
In an effort to provide data on longitudinal treatment outcomes in real-world populations, a team of investigators launched the PROOF registry, an observational study that has been ongoing since 2013 which has been dedicated to monitoring disease progression in patients with IPF.
At the annual 2018 European Respiratory Society (ERS) International Congress held from September 15 to 19 in Paris, France, investigators reported that over 12 months of follow-up in the PROOF registry, pulmonary function remained largely stable in patients with IPF who received pirfenidone treatment. Disease progression rates seen in the PROOF study were comparable to progression rates observed over 12 months in phase 3 clinical trials.
“Patients recruited into clinical studies represent a rigorously selected population and therefore do not necessarily reflect the characteristics of IPF subjects seen in routine clinical practice,” Wim Wuyts, MD, PhD, from the Department of Respiratory Medicine at University Hospitals Leuven, told Rare Disease Report®
“Therefore, although clinical trials provide essential data regarding the efficacy and safety of treatments, the restrictive inclusion and exclusion criteria can generate uncertainty when applying results to real-world populations of patients. Generally, real-world data complements data from randomized controlled trials, typically comprising a wide range of patients in terms of disease severity, progression, and comorbidities.”
With the PROOF registry, a team of investigators assessed longitudinal changes in lung function over 24 months in patients with IPF who were administered pirfenidone for any duration of treatment. Patients from 8 centers in Luxembourg and Belgium were enrolled in the study between October 2013 and January 2016, regardless of previous treatments.
Lung function was evaluated using percent predicted forced vital capacity (FVC), Percent predicted diffusing capacity for carbon monoxide (DLco) at the time of inclusion (month 0) and at months 3, 6, 12 and 24 post-inclusion.
Of the 277 patients with IPF who were enrolled in the PROOF study, 233 (84.1%) patients were treated with pirfenidone at any point during follow-up in the PROOF registry, for any duration of treatment (ever-treated). Of the patients ever-treated with pirfenidone, 223 (95.7%) patients had a definite diagnosis of IPF while 10 (4.3%) had a probable diagnosis.
Longitudinal lung function in patients ever-treated with pirfenidone was reflected as a mean (SD) percent predicted FVC of 81.2% (19.0) and a mean (SD) percent predicted DLco of 47.0% (13.2) at month 0.
In percent predicted FVC, the mean (SD) time to 10% absolute decline was 20.1 (0.6) months. In percent predicted DLco, the mean (SD) time to 15% absolute decline was 23.4 (0.5) months.
“Data presented at this year’s ERS focus on the longitudinal changes in lung function over 24 months in patients with IPF who received pirfenidone,” Dr. Wuyts emphasized to RareDR®
. “Generally, the rates of disease progression seen in the PROOF registry are largely comparable with the progression reported in phase 3 clinical trials over 12 months. This real-word data supports the conclusion that pirfenidone reduces lung function decline in patients with IPF.”
A potential limitation identified in the registry and noted by the study authors was the relatively small population of patients located across a limited geographic area who were enrolled. Also, due to patients being lost to follow-up over time or data not being collected at all time points for all patients, some data was missing, and so, some outcomes were summarized using small sample sizes.
“In addition to clinical study data, real-world data (RWD) presented at ERS add to the growing body of evidence reaffirming the benefits of treatment of IPF with pirfenidone in daily practice,” Dr. Wuyts added. “RWD will be collected on an ongoing basis and these data will continue to be presented at medical conferences as they become available.”