title: Pirfenidone for the treatment of Hermansky-Pudlak syndrome pulmonary fibrosis.
abstract: Hermansky-Pudlak syndrome (HPS) is a rare disorder of oculocutaneous albinism, platelet dysfunction, and in some subtypes, fatal pulmonary fibrosis. There is no effective treatment for the pulmonary fibrosis except lung transplantation, but an initial trial using pirfenidone, an anti-fibrotic agent, showed promising results. The current, randomized, placebo-controlled, prospective, double-blind trial investigated the safety and efficacy of pirfenidone for mild to moderate HPS-1 and 4 pulmonary fibrosis. Subjects were evaluated every 4 months at the National Institutes of Health Clinical Center, and the primary outcome parameter was change in forced vital capacity using repeated measures analysis with random coefficients. Thirty-five subjects with HPS-1 pulmonary fibrosis were enrolled during a 4-year interval; 23 subjects received pirfenidone and 12 received placebo. Four subjects withdrew from the trial, 3 subjects died, and 10 serious adverse events were reported. Both groups experienced similar side effects, especially gastroesophageal reflux. Interim analysis of the primary outcome parameter, performed 12 months after 30 patients were enrolled, showed no statistical difference between the placebo and pirfenidone groups, and the study was stopped due to futility. There were no significant safety concerns. Other clinical trials are indicated to identify single or multiple drug regimens that may be effective in treatment for progressive HPS-1 pulmonary fibrosis.
authors.affiliation: Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. obrienke@mail.nih.gov
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Brien
authors.forename: James
authors.initials: J
authors.lastname: Troendle
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.forename: Jose
authors.initials: J
authors.lastname: Salas
authors.forename: Hilda
authors.initials: H
authors.lastname: Cardona
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yao
authors.forename: Isa
authors.initials: I
authors.lastname: Bernardini
authors.forename: Richard
authors.initials: R
authors.lastname: Hess
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000328:Adult; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D011728:Pyridones / Q000627:therapeutic use*; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D011728:Pyridones; C093844:pirfenidone