Prolonged treatment with open-label pirfenidone in Hermansky-Pudlak syndrome pulmonary fibrosis

Mol Genet Metab. 2018 Sep;125(1-2):168-173. doi: 10.1016/j.ymgme.2018.07.012. Epub 2018 Jul 23.


Purpose: Limited information is available regarding chronic treatment with pirfenidone, an anti-fibrotic drug. Effects of long-term open-label pirfenidone were evaluated in a small cohort with Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder with highly penetrant pulmonary fibrosis.

Results: Three patients with HPS pulmonary fibrosis treated with open-label pirfenidone and twenty-one historical controls randomized to placebo were studied at a single center. Mean duration of treatment with pirfenidone for 3 patients with HPS pulmonary fibrosis was 13.1 years. Annual changes in FVC and DLCO with pirfenidone treatment were 0.46 and - 0.93% predicted, respectively. In comparison, historical controls randomized to receive placebo experienced mean annual changes in FVC and DLCO of -4.4 and - 2.3% predicted, respectively. High-resolution computed tomography (HRCT) scans revealed improved ground glass opacities with development of minimal interstitial reticulations in 1 patient after 12.8 years of treatment with pirfenidone. Slowly progressive increase in bilateral interstitial fibrosis developed in a different patient, who received pirfenidone for 18.1 years and died at 73 years of age due to HPS pulmonary fibrosis. Another patient treated with pirfenidone for 8.4 years had attenuated ground glass opacification on HRCT scan and improved oxygenation; this patient died due to chronic complications from colitis, and not pulmonary fibrosis. Adverse effects were generally limited to mild gastrointestinal discomfort and transient elevations of alanine aminotransferase in one patient.

Conclusions: Chronic treatment with pirfenidone may provide clinical benefit with few adverse effects for some patients with HPS pulmonary fibrosis. These results suggest that compassionate use of pirfenidone could be considered on a case-by-case basis for patients with HPS pulmonary fibrosis.

Keywords: Hermansky-Pudlak syndrome; pirfenidone; pulmonary fibrosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Female
  • Hermanski-Pudlak Syndrome / complications
  • Hermanski-Pudlak Syndrome / diagnostic imaging
  • Hermanski-Pudlak Syndrome / drug therapy*
  • Hermanski-Pudlak Syndrome / pathology
  • Humans
  • Lung / diagnostic imaging
  • Lung / pathology
  • Male
  • Middle Aged
  • Pulmonary Fibrosis / complications
  • Pulmonary Fibrosis / diagnostic imaging
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / pathology
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Tomography, X-Ray Computed


  • Pyridones
  • pirfenidone