Pharmacological treatment of idiopathic pulmonary fibrosis: From the past to the future

European Respiratory Review

Volumn 22, Issue 129, 2013, Pages 281-291

  Antoniou, Katerina M ^a   Margaritopoulos, George A ^a   Siafakas, Nikos M ^a  

^a UNIVERSITY HOSPITAL OF HERAKLION   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

AB 0024; ACETYLCYSTEINE; AMBRISENTAN; ANTICOAGULANT AGENT; AZATHIOPRINE; BOSENTAN; CARLUMAB; COLCHICINE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; ETANERCEPT; FG 3019; FRESOLIMUMAB; GAMMA INTERFERON; IMATINIB; INTERLEUKIN 13 ANTIBODY; LOW MOLECULAR WEIGHT HEPARIN; MACITENTAN; MONOCLONAL ANTIBODY; NINTEDANIB; PIRFENIDONE; PLACEBO; PREDNISOLONE; PREDNISONE; QAX 576; SILDENAFIL; STX 100; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; WARFARIN;

BLEEDING; DOSE RESPONSE; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; FIBROSING ALVEOLITIS; GASTROINTESTINAL SYMPTOM; HUMAN; LIVER TOXICITY; LOW DRUG DOSE; LUNG FUNCTION; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHOTOSENSITIVITY; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STUDY DESIGN; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

ANIMALS; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; IDIOPATHIC PULMONARY FIBROSIS; PYRIDONES; RESPIRATORY SYSTEM AGENTS; TREATMENT OUTCOME;

EID: 84883413596     PISSN: 09059180     EISSN: 16000617     Source Type: Journal    
DOI: 10.1183/09059180.00002113     Document Type: Review

References (87)

1. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183: 788-824.
2. Vancheri C, du Bois RM. A progression-free end-point for idiopathic pulmonary fibrosis trials: lessons from cancer. Eur Respir J 2013; 41: 262-269.
3. Nalysnyk L, Cid-Ruzafa J, Rotella P, et al. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev 2012; 21: 355-361.
4. du Bois RM. An earlier and more confident diagnosis of idiopathic pulmonary fibrosis. Eur Respir Rev 2012; 21: 141-146.
5. Margaritopoulos GA, Romagnoli M, Poletti V, et al. Recent advances in the pathogenesis and clinical evaluation of pulmonary fibrosis. Eur Respir Rev 2012; 21: 48-56.
6. Wuyts WA, Agostini C, Antoniou KM, et al. The pathogenesis of pulmonary fibrosis: a moving target. Eur Respir J 2013; 41: 1207-1218.
7. Günther A, Korfei M, Mahavadi P, et al. Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis. Eur Respir Rev 2012; 21: 152-160.
8. Selman M, King TE, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 2001; 134: 136-151.
9. Lasithiotaki I, Antoniou KM, Vlahava VM, et al. Detection of herpes simplex virus type-1 in patients with fibrotic lung diseases. PLoS One 2011; 6: e27800.
10. Tcherakian C, Cottin V, Brillet PY, et al. Progression of idiopathic pulmonary fibrosis: lessons from asymmetrical disease. Thorax 2011; 66: 226-231.
11. Lee JS, Ryu JH, Elicker BM, et al. Gastroesophageal reflux therapy is associated with longer survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011; 184: 1390-1394.
12. Samara KD, Margaritopoulos G, Wells AU, et al. Smoking and pulmonary fibrosis: novel insights. Pulm Med 2011; 2011: 461439.
13. Maher TM, Wells AU, Laurent GJ. Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms? Eur Respir J 2007; 30: 835-839.
14. Armanios M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet 2009; 10: 45-61.
15. Coppé JP, Desprez PY, Krtolica A, et al. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 2010; 5: 99-118.
16. Chilosi M, Doglioni C, Murer B, et al. Epithelial stem cell exhaustion in the pathogenesis of idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2010; 27: 7-18.
17. Korfei M, Ruppert C, Mahavadi P, et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2008; 178: 838-846.
18. Lawson WE, Cheng DS, Degryse AL, et al. Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs. Proc Natl Acad Sci USA 2011; 108: 10562-10567.
19. Sisson TH, Mendez M, Choi K, et al. Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis. Am J Respir Crit Care Med 2010; 181: 254-263.
20. Demedts M, Behr J, Buhl R, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 2005; 353: 2229-2242.
21. Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 2012; 366: 1968-1977.
22. Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J 2010; 35: 821-829.
23. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011; 377: 1760-1769.
24. Noth I, Anstrom KJ, Calvert SB, et al. A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2012; 186: 88-95.
25. Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 2011; 365: 1079-1087.
26. Daniels CE, Lasky JA, Limper AH, et al. Imatinib treatment for idiopathic pulmonary fibrosis: randomized placebocontrolled trial results. Am J Respir Crit Care Med 2010; 181: 604-610.
27. Zisman DA, Schwarz M, Anstrom KJ, et al. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med 2010; 363: 620-628.
28. King TE, Behr J, Brown KK, et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2008; 177: 75-81.
29. King TE, Brown KK, Raghu G, et al. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011; 184: 92-99.
30. Raghu G, Behr J, Brown K, et al. Artemis-IPF: a placebo-controlled trial of ambrisentan in idiopathic pulmonary fibrosis. B93. Clinical Trials in Idiopathic Pulmonary Fibrosis and Sarcoidosis. May 1, 2012; A3632.
31. Raghu G, Million-Rousseau R, Morganti A, et al. Efficacy and safety of macitentan in idiopathic pulmonary fibrosis: results of a prospective, randomized, double-blind, placebo-controlled trial. B93. Clinical Trials in Idiopathic Pulmonary Fibrosis and Sarcoidosis. May 1, 2012; A3631.
32. Raghu G, Brown KK, Bradford WZ, et al. A placebo-controlled trial of interferon-c-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 2004; 350: 125-133.
33. King TE Jr, Albera C, Bradford WZ, et al. Effect of interferon-c-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. Lancet 2009; 374: 222-228.
34. du Bois RM. Idiopathic pulmonary fibrosis: present understanding and future options. Eur Respir Rev 2011; 20: 132-133.
35. Cottin V. Changing the idiopathic pulmonary fibrosis treatment approach and improving patient outcomes. Eur Respir Rev 2012; 21: 161-167.
36. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000; 161: 646-664.
37. Raghu G, Depaso WJ, Cain K, et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. Am Rev Respir Dis 1991; 144: 291-296.
38. Richeldi L. Assessing the treatment effect from multiple trials in idiopathic pulmonary fibrosis. Eur Respir Rev 2012; 21: 147-151.
39. Spagnolo P, Del Giovane C, Luppi F, et al. Non-steroid agents for idiopathic pulmonary fibrosis. Cochrane Database Syst Rev 2010; 9: CD003134.
40. Behr J, Maier K, Degenkolb B, et al. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med 1997; 156: 1897-1901.
41. Behr J, Degenkolb B, Krombach F, et al. Intracellular glutathione and bronchoalveolar cells in fibrosing alveolitis: effects of N-acetylcysteine. Eur Respir J 2002; 19: 906-911.
42. NIH News. Commonly used three-drug regimen for idiopathic pulmonary fibrosis found harmful. Bethesda, National Institutes of Health, October 21, 2011. www.nih.gov/news/health/oct2011/nhlbi-21.htm
43. Wells AU, Behr J, Costabel U, et al. Triple therapy in idiopathic pulmonary fibrosis: an alarming press release. Eur Respir J 2012; 39: 805-806.
44. Maher TM. Pirfenidone in idiopathic pulmonary fibrosis. Drugs Today (Barc) 2010; 46: 473-482.
45. Schaefer CJ, Ruhrmund DW, Pan L, et al. Antifibrotic activities of pirfenidone in animal models. Eur Respir Rev 2011; 20: 85-97.
46. Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on transforming growth factor-b gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther 1999; 291: 367-373.
47. Gurujeyalakshmi G, Hollinger MA, Giri SN. Pirfenidone inhibits PDGF isoforms in bleomycin hamster model of lung fibrosis at the translational level. Am J Physiol 1999; 276: L311-L318.
48. Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on procollagen gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther 1999; 289: 211-218.
49. Oku H, Shimizu T, Kawabata T, et al. Antifibrotic action of pirfenidone and prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced murine pulmonary fibrosis. Eur J Pharmacol 2008; 590: 400-408.
50. Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005; 171: 1040-1047.
51. Costabel U, Albera C, Cohen A, et al. The long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF): Interim data from the RECAP extension study. Eur Respir J 2011; 38: Suppl. 55, A174.
52. Chambers RC. Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? Br J Pharmacol 2008; 153: Suppl. 1, S367-S378.
53. Scotton CJ, Krupiczojc MA, Königshoff M, et al. Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. J Clin Invest 2009; 119: 2550-2563.
54. Wygrecka M, Kwapiszewska G, Jablonska E, et al. Role of protease-activated receptor-2 in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011; 183: 1703-1714.
55. Sode BF, Dahl M, Nielsen SF, et al. Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med 2010; 181: 1085-1092.
56. Kubo H, Nakayama K, Yanai M, et al. Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 2005; 128: 1475-1482.
57. Tzouvelekis A, Margaritopoulos G, Loukides S, et al. Warfarin in idiopathic pulmonary fibrosis: friend or foe, is it a matter of genes and heparin? Am J Respir Crit Care Med 2013; 187: 213-214.
58. Allen JT, Spiteri MA. Growth factors in idiopathic pulmonary fibrosis: relative roles. Respir Res 2002; 3: 13.
59. Daniels CE, Wilkes MC, Edens M, et al. Imatinib mesylate inhibits the profibrogenic activity of TGF-b and prevents bleomycin-mediated lung fibrosis. J Clin Invest 2004; 114: 1308-1316.
60. Aono Y, Nishioka Y, Inayama M, et al. Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice. Am J Respir Crit Care Med 2005; 171: 1279-1285.
61. Vuorinen K, Gao F, Oury TD, et al. Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Exp Lung Res 2007; 33: 357-373.
62. Clark JG, Dedon TF, Wayner EA, et al. Effects of interferon-c on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts. J Clin Invest 1989; 83: 1505-1511.
63. Narayanan AS, Whithey J, Souza A, et al. Effect of gamma-interferon on collagen synthesis by normal and fibrotic human lung fibroblasts. Chest 1992; 101: 1326-1331.
64. Okada T, Sugie I, Aisaka K. Effects of gamma-interferon on collagen and histamine content in bleomycin-induced lung fibrosis in rats. Lymphokine Cytokine Res 1993; 12: 87-91.
65. Gurujeyalakshmi G, Giri SN. Molecular mechanisms of antifibrotic effect of interferon-c in bleomycin-mouse model of lung fibrosis: downregulation of TGF-b and procollagen I and III gene expression. Exp Lung Res 1995; 21: 791-808.
66. Ziesche R, Hofbauer E, Wittmann K, et al. A preliminary study of long-term treatment with interferon-c-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med 1999; 341: 1264-1269.
67. Raghu G, Brown KK, Costabel U, et al. Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am J Respir Crit Care Med 2008; 178: 948-955.
68. Hancock A, Armstrong L, Gama R, et al. Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol 1998; 18: 60-65.
69. Moore BB, Kolodsick JE, Thannickal VJ, et al. CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury. Am J Pathol 2005; 166: 675-684.
70. Murray LA, Argentieri RL, Farrell FX, et al. Hyper-responsiveness of IPF/UIP fibroblasts: interplay between TGFb1, IL-13 and CCL2. Int J Biochem Cell Biol 2008; 40: 2174-2182.
71. Lipson KE, Wong C, Teng Y, et al. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair 2012; 5: Suppl. 1, S24.
72. Akiri G, Sabo E, Dafni H, et al. Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo. Cancer Res 2003; 63: 1657-1666.
73. Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med 2010; 16: 1009-1017.
74. Vadasz Z, Kessler O, Akiri G, et al. Abnormal deposition of collagen around hepatocytes in Wilson's disease is associated with hepatocyte specific expression of lysyl oxidase and lysyl oxidase like protein-2. J Hepatol 2005; 43: 499-507.
75. Tzouvelekis A, Antoniadis A, Bouros D. Stem cell therapy in pulmonary fibrosis. Curr Opin Pulm Med 2011; 17: 368-373.
76. Antoniou KM, Margaritopoulos GA, Proklou A, et al. Investigation of telomerase/telomeres system in bone marrow mesenchymal stem cells derived from IPF and RA-UIP. J Inflamm (Lond) 2012; 9: 27.
77. Antoniou KM, Papadaki HA, Soufla G, et al. Investigation of bone marrow mesenchymal stem cells (BM MSCs) involvement in idiopathic pulmonary fibrosis (IPF). Respir Med 2010; 104: 1535-1542.
78. Toonkel RL, Hare JM, Matthay MA, et al. Mesenchymal stem cells and idiopathic pulmonary fibrosis: potential for clinical testing. Am J Respir Crit Care Med 2013 [In press DOI:10.1164/rccm.201207-1204PP].
79. Noth I, Zangan SM, Soares RV, et al. Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis. Eur Respir J 2012; 39: 344-351.
80. Lee JS, Song JW, Wolters PJ, et al. Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 2012; 39: 352-358.
81. Allen S, Raut S, Woollard J, et al. Low dose diamorphine reduces breathlessness without causing a fall in oxygen saturation in elderly patients with end-stage idiopathic pulmonary fibrosis. Palliat Med 2005; 19: 128-130.
82. Horton MR, Santopietro V, Mathew L, et al. Thalidomide for the treatment of cough in idiopathic pulmonary fibrosis: a randomized trial. Ann Intern Med 2012; 157: 398-406.
83. Hope-Gill BDM, Hilldrup S, Davies C, et al. A study of the cough reflex in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2003; 168: 995-1002.
84. Raghu G, Collard HR, Anstrom KJ, et al. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Respir Crit Care Med 2012; 185: 1044-1048.
85. Wells AU, Behr J, Costabel U, et al. Hot of the breath: mortality as a primary end-point in IPF treatment trials: the best is the enemy of the good. Thorax 2012; 67: 938-940.
86. Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J 2010; 35: 830-836.
87. Bria E, Gralla RJ, Raftopoulos H, et al. Magnitude of benefit of adjuvant chemotherapy for non-small cell lung cancer: meta-analysis of randomized clinical trials. Lung Cancer 2009; 63: 50-57.