Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome.
Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency and, in patients with HPS1 gene mutations, a progressive, fatal pulmonary fibrosis. We investigated the safety and efficacy of an antifibrotic agent, pirfenidone (800 mg, t.i.d.), in treating 21 adult Puerto Rican HPS patients, including 20 homozygous for the same HPS1 mutation. Patients were examined every 4 months for up to 44 months in a randomized, placebo-controlled trial, with rate of change in pulmonary function values as outcome parameters. Using the complete data set of 130 patient admissions, a repeated measures model showed that 11 pirfenidone-treated patients lost FVC at a rate 5% of predicted ( approximately 400 mL) per year slower than 10 placebo-treated patients (p=0.001). A random coefficients model showed no significant difference. However, using data restricted to patients with an initial FVC >50% of predicted, both models showed the pirfenidone group losing FVC (p<0.022), FEV(1) (p<0.0007), TLC (p<0.001), and DL(CO) (p<0.122) at a rate approximately 8%/year slower than the placebo group. Clinical and laboratory side effects were similar in the two groups. Pirfenidone appears to slow the progression of pulmonary fibrosis in HPS patients who have significant residual lung function.
Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. bgahl@helix.nih.gov
William A
WA
Gahl
Mark
M
Brantly
James
J
Troendle
Nilo A
NA
Avila
Antonio
A
Padua
Carlos
C
Montalvo
Hilda
H
Cardona
Karim Anton
KA
Calis
Bernadette
B
Gochuico
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010919:Placebos; D011658:Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D010919:Placebos; D011728:Pyridones; C093844:pirfenidone