PURPOSE: Progressive pulmonary fibrosis is a leading cause of death in individuals with Hermansky-Pudlak syndrome (HPS)-1. Treatment for pulmonary fibrosis in HPS-1 is limited, but one potential drug is pirfenidone. The purpose of this study is to retrospectively review medical records, pulmonary function tests (PFTs), and high-resolution computed tomography (HRCT) scan findings of three subjects who have been treated long-term with pirfenidone.
METHODS: Three subjects, who were originally enrolled in a clinical trial investigating pirfenidone for treatment of pulmonary fibrosis in HPS-1, received pirfenidone for five to eight years following completion of this trial. Data after initiation of pirfenidone were retrospectively studied.
RESULTS: Subjects were diagnosed with HPS-1 by genotyping; their ages were 24, 43, and 55 years when treatment with pirfenidone was begun. After initiation of pirfenidone, two subjects noted stabilization of dyspnea on exertion. Serial PFTs revealed gradual decline in DLCO and stable FVC over at least five years; HRCT scans revealed improvement of minimal interstitial lung disease and ground glass opacification in one subject and slight progression of mild fibrosis in the other subject. Supplemental oxygen was discontinued for a third subject, who experienced improvement in dyspnea. PFTs revealed mild improvement in DLCO and stable FVC over five years; HRCT scans revealed stable ground glass opacification with slight progression of mild fibrosis. One subject experienced mild gastrointestinal discomfort probably related to pirfenidone.
CONCLUSION: Retrospective analysis of three subjects reveals that treatment with pirfenidone for several years may provide benefit with minimal side effects for a subset of individuals with the pulmonary fibrosis of HPS-1. Further studies investigating pirfenidone for treatment of pulmonary fibrosis in HPS or in other subpopulations with fibrotic lung disease are needed.
CLINICAL IMPLICATIONS: Long term treatment with pirfenidone for pulmonary fibrosis in HPS-1 may be beneficial and appears to be well-tolerated. A double-blind, placebo-controlled trial investigating pirfenidone for treatment of mild to moderate pulmonary fibrosis in HPS-1 is currently open for enrollment at NIH.
DISCLOSURE: Bernadette Gochuico, No Financial Disclosure Information; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Pirfenidone is an antifibrotic drug that is not yet approved by the FDA and is being investigated in a double-blind, placebo-controlled trial investigating its use for treatment for pulmonary fibrosis in Hermansky-Pudlak syndrome.