A Retrospective Analysis of Pirfenidone in Pulmonary Fibrosis Patients

Abstract

SESSION TITLE: Diffuse Lung Disease I SESSION TYPE: Original Investigation Slide PRESENTED ON: Sunday, October 29, 2017 at 03:15 PM - 04:15 PM PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia with no known cause and a poor prognosis. Until 2014, there were no FDA-approved treatments available for IPF. The 2015 guidelines recommend the use of two new antifibrotic drugs: pirfenidone (PFD) and nintedanib (NIN). There is limited long-term published data available for the efficacy and safety of PFD in IPF treatment, particularly within the United States. This retrospective analysis offers 2 years of follow-up for patients receiving PFD. METHODS: Records were reviewed for 52 consecutive patients ≥19 years who received PFD for outpatient IPF treatment at a single academic medical center clinic from 2011-2016. Patients were identified from the clinic records or had participated in the pirfenidone Early Access Program. Data were collected on demographics, pulmonary function, utilization of PFD, and adverse events. The primary endpoint for efficacy was defined as change in forced vital capacity (FVC). Secondary endpoints include oxygen requirements, six-minute walk distance, dyspnea, tolerability of PFD therapy, and death. RESULTS: Study subjects were on average 70 years old, 75% male, 92% Caucasian, and had an average of 4 comorbidities. The most common comorbidities were cardiovascular (88%) and endocrine (48%). Patients were diagnosed with IPF for an average of 770 days prior to receiving PFD. Mean follow-up time after starting PFD treatment was 784 days. FVC declined by 84 mL at year 1 and 204 mL at year 2 from baseline. Six-minute walk distance was reduced by 17 m at year 1 and 42 m at year 2. Levels of dyspnea based on the Borg scale increased by 0.75 points at year 1 and 1.75 at year 2. Oxygen requirements at rest increased by 0.45 L and 1.11 L at 1 and 2 years, while oxygen requirements with activity increased by 1.45 L and 2 L at 1 and 2 years from baseline, respectively. There were 8 deaths total (15%) with a mean time to death of 437 days. Approximately 50% of all patients receiving PFD therapy had at least 1 documented adverse event. The most common was nausea in 27%. On average, subjects received PFD for 662 days (range 18-1557 days). PFD was discontinued in 29% of patients. GI adverse events were the most common reason to discontinue therapy (15%). Other reasons for discontinuation include therapeutic switch to NIN, transition to hospice care, and lack of efficacy. CONCLUSIONS: This patient sample was consistent with the ASCEND trial with regard to age, sex, and race. This single-center data revealed an FVC decline of 84 mL at 1 year. The 2-year decline was 204 mL, which was similar to 12-month data in the ASCEND trial. Oxygen requirements increased over 2 years, which may reflect a survivor bias. Although 50% of patients experienced an adverse event with PFD therapy, only 15% required discontinuation. Tolerability was comparable between this study and the ASCEND trial. Limitations of this study include single-center data analysis and those limits inherent to the retrospective study design. CLINICAL IMPLICATIONS: As a treatment for IPF, PFD has limited published data from the United States past 1 year. This study demonstrates real world experience using PFD at a single-center academic practice clinic beyond 2 years. DISCLOSURE: The following authors have nothing to disclose: Lauren Bricker, Stanley Thomas, Mary Pote, Lee Morrow, Mark Malesker No Product/Research Disclosure Information