1932

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease that has long eluded therapy. Prognosis remains very poor, and currently lung transplantation offers the only hope of survival. Recently, great strides have been made in the development of pharmaceutical therapy to treat IPF. Pirfenidone, an oral antifibrotic agent, has been shown to slow progression of the disease and improve progression-free survival, offering new hope for patients suffering from IPF.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-120214-013614
2016-01-14
2024-12-04
Loading full text...

Full text loading...

/deliver/fulltext/med/67/1/annurev-med-120214-013614.html?itemId=/content/journals/10.1146/annurev-med-120214-013614&mimeType=html&fmt=ahah

Literature Cited

  1. Fernandez IE, Eickelberg O. 1.  2012. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet 380:680–88 [Google Scholar]
  2. Wuyts WA, Agostini C, Antoniou KM. 2.  et al. 2013. The pathogenesis of pulmonary fibrosis: a moving target. Eur. Respir. J. 41:1207–18 [Google Scholar]
  3. Seibold MA, Wise AL, Speer MC. 3.  et al. 2011. A common MUC5B promoter polymorphism and pulmonary fibrosis. N. Engl. J. Med 364:161503–12 [Google Scholar]
  4. Noble PW, Barkauskas CE, Jiang D. 4.  2012. Pulmonary fibrosis: patterns and perpetrators. J. Clin. Investig. 122:82756–62 [Google Scholar]
  5. Ley B, Collard HR, King TE Jr. 5.  2011. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 183:431–40 [Google Scholar]
  6. 6. American Thoracic Society (ATS) and European Respiratory Society (ERS) 2000. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am. J. Respir. Crit. Care Med. 161:646–64 [Google Scholar]
  7. Demedts M, Behr J, Buhl R. 7.  et al. 2005. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 353:2229–42 [Google Scholar]
  8. 8. The Idiopathic Pulmonary Fibrosis Clinical Research Network 2012. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N. Engl. J. Med. 366:1968–77 [Google Scholar]
  9. Raghu G, Collard HR, Egan JJ. 9.  et al. 2011. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am. J. Respir. Crit. Care Med. 183:788–824 [Google Scholar]
  10. Martinez FJ, de Andrade JA, Anstrom KJ. 10.  et al. 2014. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. Idiopathic Pulmonary Fibrosis Clinical Research Network. N. Engl. J. Med. 370:2093–101 [Google Scholar]
  11. Schaefer CJ, Ruhrmund DW, Pan L. 11.  et al. 2011. Antifibrotic activities of pirfenidone in animal models. Eur. Respir. Rev. 20:85–97 [Google Scholar]
  12. Nakazato H, Oku H, Yamane Y. 12.  et al. 2002. A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor alpha at the translational level. Eur. J. Pharmacol. 446:177–85 [Google Scholar]
  13. van Oosten BW, Barkhof F, Scholten PE. 13.  et al. 1998. Increased production of tumor necrosis factor alpha, and not of interferon gamma, preceding disease activity in patients with multiple sclerosis. Arch. Neurol. 55:793–98 [Google Scholar]
  14. Bowen JD, Maravilla K, Margolin SB. 14.  2003. Open-label study of pirfenidone in patients with progressive forms of multiple sclerosis. Mult. Scler. 9:280–83 [Google Scholar]
  15. Walker JE, Giri SN, Margolin SB. 15.  2005. A double-blind, randomized, controlled study of oral pirfenidone for treatment of secondary progressive multiple sclerosis. Mult. Scler. 11:149–58 [Google Scholar]
  16. Walker JE, Margolin SB. 16.  2001. Pirfenidone for chronic progressive multiple sclerosis. Mult. Scler. 7:305–12 [Google Scholar]
  17. van Oosten BW, Barkhof F, Truyen L. 17.  et al. 1996. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47:1531–34 [Google Scholar]
  18. Sicotte NL, Voskuhl RR. 18.  2001. Onset of multiple sclerosis associated with anti-TNF therapy. Neurology 57:1885–88 [Google Scholar]
  19. Grattendick KJ, Nakashima JM, Feng L. 19.  et al. 2008. Effects of three anti-TNF-α drugs: etanercept, infliximab and pirfenidone on release of TNF-α in medium and TNF-α associated with the cell in vitro. Int. Immunopharmacol. 8:679–87 [Google Scholar]
  20. Conte E, Gili E, Fagone E. 20.  et al. 2014. Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts. Eur. J. Pharm. Sci. 58:13–19 [Google Scholar]
  21. Dong Y, Geng Y, Li L. 21.  et al. 2015. Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice. J. Exp. Med. 212:2235–52 [Google Scholar]
  22. Sime PJ, Xing Z, Graham FL. 22.  et al. 1997. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J. Clin. Investig. 100:768–76 [Google Scholar]
  23. Wang Q, Wang Y, Hyde DM. 23.  et al. 1999. Reduction of bleomycin induced lung fibrosis by transforming growth factor beta soluble receptor in hamsters. Thorax 54:805–12 [Google Scholar]
  24. Iyer SN, Gurujeyalakshmi G, Giri SN. 24.  1999. Effects of pirfenidone on transforming growth factor-beta gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J. Pharmacol. Exp. Ther. 291:367–73 [Google Scholar]
  25. Shihab FS, Bennett WM, Yi H, Andoh TF. 25.  2002. Pirfenidone treatment decreases transforming growth factor-beta1 and matrix proteins and ameliorates fibrosis in chronic cyclosporine nephrotoxicity. Am. J. Transplant. 2:111–19 [Google Scholar]
  26. Kaneko M, Inoue H, Nakazawa R. 26.  et al. 1998. Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts. Clin. Exp. Immunol. 113:172–76 [Google Scholar]
  27. Xiang XH, Jiang TP, Zhang S. 27.  et al. 2015. Pirfenidone inhibits proliferation, arrests the cell cycle, and downregulates heat shock protein-47 and collagen type I in rat hepatic stellate cells in vitro. Mol. Med. Rep. 12:1309–14 [Google Scholar]
  28. Kirillov V, Siler JT, Ramadass M. 28.  et al. 2015. Sustained activation of toll-like receptor 9 induces an invasive phenotype in lung fibroblasts: possible implications in idiopathic pulmonary fibrosis. Am. J. Pathol. 185:4943–57 [Google Scholar]
  29. 29.  2014. Esbriet (pirfenidone). Highlights of prescribing information. Brisbane, CA: InterMune Inc http://www.gene.com/download/pdf/esbriet_prescribing.pdf [Google Scholar]
  30. Raghu G, Johnson WC, Lockhart D. 30.  et al. 1999. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label Phase II study. Am. J. Respir. Crit. Care Med. 159:1061–69 [Google Scholar]
  31. Azuma A, Nukiwa T, Tsuboi E. 31.  et al. 2005. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 171:1040–47 [Google Scholar]
  32. Taniguchi H, Ebina M, Kondoh Y. 32.  et al. 2010. Pirfenidone in idiopathic pulmonary fibrosis. Eur. Respir. J. 35:821–29 [Google Scholar]
  33. Noble PW, Albera C, Bradford WZ. 33.  et al. 2011. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 377:1760–69 [Google Scholar]
  34. Spagnolo P, Del Giovane C, Luppi F. 34.  et al. 2010. Non-steroid agents for idiopathic pulmonary fibrosis. Cochrane Database Syst. Rev. 9:CD003134 [Google Scholar]
  35. King TE Jr, Bradford WZ, Castro-Bernardini S. 35.  et al. 2014. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N. Engl. J. Med. 370:2083–92 [Google Scholar]
  36. Raghu G, Collard HR, Anstrom KJ. 36.  et al. 2012. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am. J. Respir. Crit. Care Med. 185:1044–48 [Google Scholar]
  37. du Bois RM, Weycker D, Albera C. 37.  et al. 2011. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am. J. Respir. Crit. Care Med. 184:1382–89 [Google Scholar]
  38. Collard HR, King TE Jr, Bartelson BB. 38.  et al. 2003. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 168:538–42 [Google Scholar]
  39. Lederer DJ, Bradfrod WZ, Fagan EA. 39.  et al. 2015. Sensitivity analyses of the change in forced vital capacity in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis. Chest 148:1196–201 [Google Scholar]
  40. Costabel U, Albera C, Cohen A. 40.  et al. 2011. The long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF): interim data from the RECAP extension study. Eur. Respir. J. 38:Suppl. 55174s [Google Scholar]
  41. Costabel U, Albera C, Bradford WZ. 41.  et al. 2014. Analysis of lung function and survival in RECAP: an open-label extension study of pirfenidone in patients with idiopathic pulmonary fibrosis. Sarcoidosis Vasc. Diffuse Lung Dis. 31:198–205 [Google Scholar]
  42. Koschel D, Cottin V, Skold M. 42.  et al. 2014. Pirfenidone post-authorisation safety registry (PASSPORT)—interim analysis of IPF treatment. Eur. Respir. J. 44:Suppl. 581904 [Google Scholar]
  43. Cottin V, Maher T. 43.  2015. Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis. Eur. Respir. Rev. 24:135, 58–64 [Google Scholar]
  44. Duck A, Pigram L. Errhalt P44.  et al. 2015. IPF Care: a support program for patients with idiopathic pulmonary fibrosis treated with pirfenidone in Europe. Adv. Ther. 32:287–107 [Google Scholar]
  45. Loeh B, Drakopanagiotakis F, Bandelli GP. 45.  et al. 2015. Intraindividual response to treatment with pirfenidone in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 191:110–13 [Google Scholar]
  46. Behr J, Kreuter M, Hoeper M. 46.  et al. 2015. Management of patients with idiopathic pulmonary fibrosis in clinical practice: the INSIGHTS-IPF registry. Eur. Resp. J. 46:1186–96 [Google Scholar]
/content/journals/10.1146/annurev-med-120214-013614
Loading
/content/journals/10.1146/annurev-med-120214-013614
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error