Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis

References

• 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.
   PubMed Web of Science ®Google Scholar
• Chaudhary NI, Roth GJ, Hilberg F, et al. Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. Eur Respir J. 2007;29:976–985.
   PubMed Web of Science ®Google Scholar
• Coward WR, Saini G, Jenkins G. The pathogenesis of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2010;4:367–388.
   PubMedGoogle Scholar
• Wollin L, Maillet I, Quesniaux V, Holweg A, Ryffel B. Anti-fibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014;349:209–220.
   PubMed Web of Science ®Google Scholar
• Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774–4782.
   PubMed Web of Science ®Google Scholar
• Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079–1087.
   PubMed Web of Science ®Google Scholar
• Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–2082.
   PubMed Web of Science ®Google Scholar
• National Clinical Guideline Centre (UK). Diagnosis and Management of Suspected Idiopathic Pulmonary Fibrosis: Idiopathic Pulmonary Fibrosis [Internet]. London: Royal College of Physicians (UK); 2013.
   Google Scholar
• Landells LJ, Naidoo B, Robertson J, Clark P. NICE guidance on pirfenidone for treating idiopathic pulmonary fibrosis. Lancet Respir Med. 2013;1(3):191–192.
   PubMed Web of Science ®Google Scholar
• Xaubet A, Behr J, Bendstrup E, et al. Review of IPF diagnosis and management recommendations in Europe. Sarcoidosis Vasc Diffuse Lung Dis. 2013;30(4):249–261.
   PubMed Web of Science ®Google Scholar
• Günther A, Korfei M, Mahavadi P, von der Beck D, Ruppert C, Markart P. Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis. Eur Respir Rev. 2012;21:152–160.
   PubMedGoogle Scholar
• Noble PW, Barkauskas CE, Jiang D. Pulmonary fibrosis: patterns and perpetrators. J Clin Invest. 2012;122:2756–2762.
   PubMed Web of Science ®Google Scholar
• Herdin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79:1283–1316.
   PubMed Web of Science ®Google Scholar
• Li X, Eriksson U. Novel PDGF family members. PDGF-C and PDGF-D. Cytokine Growth Factor Rev. 2003;14:91–98.
   PubMed Web of Science ®Google Scholar
• Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22:1276–1312.
   PubMed Web of Science ®Google Scholar
• Boström H, Willetts K, Pekny M, et al. PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis. Cell. 1996;14:863–873.
   Google Scholar
• Soriano P. The PDGFa receptor is required for neural crest cell development and for normal patterning of the somites. Development. 1997;124:2691–2700.
   PubMed Web of Science ®Google Scholar
• Levéen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C. Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev. 1994;8:1875–1887.
   PubMed Web of Science ®Google Scholar
• Soriano P. Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. Genes Dev. 1996;8:1888–1896.
   Web of Science ®Google Scholar
• McGowan SE, Grossmann RE, Kimani PW, Holmes AJ. Platelet-derived growth factor receptor-alpha-expressing cells localize to the alveolar entry ring and have characteristics of myofibroblasts during pulmonary alveolar septal formation. Anat Rec (Hoboken). 2008;291:1649–1661.
   PubMedGoogle Scholar
• Maeda A, Hiyama K, Yamakido H, Ishioka S, Yamakido M. Increased expression of platelet-derived growth factor A and insulin-like growth factor-I in BAL cells during the development of bleomycin-induced pulmonary fibrosis in mice. Chest. 1996;109:780–786.
   PubMed Web of Science ®Google Scholar
• Walsh J, Absher M, Kelley J. Variable expression of platelet-derived growth factor family proteins in acute lung injury. Am J Respir Cell Mol Biol. 1993;9:637–644.
   PubMed Web of Science ®Google Scholar
• Zhuo Y, Zhang J, Laboy M, Lasky JA. Modulation of PDGF-C and PDGF-D expression during bleomycin-induced lung fibrosis. Am J Physiol Lung Cell Mol Physiol. 2004;286:L182–L188.
   PubMed Web of Science ®Google Scholar
• Shimizu S, Gabazza EC, Taguchi O, et al. Activated protein C inhibits the expression of platelet-derived growth factor in the lung. Am J Respir Crit Care Med. 2003;167:1416–1426.
   PubMed Web of Science ®Google Scholar
• Yoshida M, Sakuma J, Hayashi S, et al. A histologically distinctive interstitial pneumonia induced by overexpression of the interleukin 6, transforming growth factor beta 1, or platelet-derived growth factor B gene. Proc Natl Acad Sci U S A. 1995;92:9570–9574.
   PubMed Web of Science ®Google Scholar
• Antoniades HN, Bravo MA, Avila RE, et al. Platelet-derived growth factor in idiopathic pulmonary fibrosis. J Clin Invest. 1990;86:1055–1064.
   PubMed Web of Science ®Google Scholar
• Homma S, Nagaoka I, Abe H, et al. Localization of platelet-derived growth factor and insulin-like growth factor I in the fibrotic lung. Am J Respir Crit Care Med. 1995;152:2084–2089.
   PubMed Web of Science ®Google Scholar
• Gochuico BR, Avila NA, Chow CK, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med. 2008;168:159–166.
   PubMedGoogle Scholar
• Rice AB, Moomaw CR, Morgan DL, Bonner JC. Specific inhibitors of platelet-derived growth factor or epidermal growth factor receptor tyrosine kinase reduce pulmonary fibrosis in rats. Am J Pathol. 1999;55:213–221.
   Google Scholar
• Druker BJ, Tamura S, Buchdunger E, et al. Effects of s selective inhibitor of the abl tyrosine kinase on the growth of bcr-abl positive cells. Nat Med. 1996;2:561–566.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Daniels CE, Wilkes MC, Edens M, et al. Imatinib mesylate inhibits the profibrogenic activity of TGF-β and prevents bleomycin-mediated lung fibrosis. J Clin Invest. 2004;114:1308–1316.
   PubMed Web of Science ®Google Scholar
• Abdollahi A, Li M, Ping G, et al. Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J Exp Med. 2005;201:925–935.
   PubMed Web of Science ®Google Scholar
• Yoshida M, Sakuma-Mochizuki J, Abe K, et al. In vivo gene transfer of an extracellular domain of platelet-derived growth factor beta receptor by the HVJ-liposome method ameliorates bleomycin-induced pulmonary fibrosis. Biochem Biophys Res Commun. 1999;265:503–508.
   PubMed Web of Science ®Google Scholar
• Rhee CK, Lee SH, Yoon HK, et al. Effect of nilotinib on bleomycin-induced acute lung injury and pulmonary fibrosis in mice. Respiration. 2011;82:273–287.
   PubMed Web of Science ®Google Scholar
• Nishioka Y, Azuma M, Kishi M, Aono Y. Targeting platelet-derived growth factor as a therapeutic approach in pulmonary fibrosis. J Med Invest. 2013;60(3,4):175–183.
   PubMedGoogle Scholar
• Turner N, Grose R. Fibroblast growth factor signaling: from development to cancer. Nat Rev. 2010;10:116–120.
   Google Scholar
• Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8:235–253.
   PubMed Web of Science ®Google Scholar
• Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer. 2000;7:165–197.
   PubMed Web of Science ®Google Scholar
• Hetzel M, Bachem M, Anders D, Trischler G, Faehling M. Different effects of growth factors on proliferation and matrix production of normal and fibrotic human lung fibroblasts. Lung. 2005;183:225–237.
   PubMed Web of Science ®Google Scholar
• Kanazawa S, Fujiwara T, Matsuzaki S, et al. bFGF regulates PI3-kinase-Rac1-JNK pathway and promotes fibroblast migration in wound healing. PLoS One. 2010;5:e12228.
   PubMed Web of Science ®Google Scholar
• Guzy RD, Stoilov I, Elton TJ, Mecham RP, Ornitz DM. Fibroblast growth factor 2 is required for epithelial recovery, but not for pulmonary fibrosis, in response to bleomycin. Am J Respir Cell Mol Biol. 2015;52:116–128.
   PubMed Web of Science ®Google Scholar
• Ju W, Zhihong Y, Zhiyou Z, et al. Inhibition of α-SMA by the ectodomain of FGFR2c attenuates lung fibrosis. Mol Med. 2012;18:992–1002.
   PubMed Web of Science ®Google Scholar
• Ramos C, Becerril C, Montaño M, et al. FGF-1 reverts epithelial-mesenchymal transition induced by TGF-b1 through MAPK/ERK kinase pathway. Am J Physiol Lung Cell Mol Physiol. 2010;299: L222–L231.
   PubMed Web of Science ®Google Scholar
• Ramos C, Montaño M, Becerril C, et al. Acidic fibroblast growth factor decreases a-smooth muscle actin expression and induces apoptosis in human normal lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2006;291:L871–L879.
   PubMed Web of Science ®Google Scholar
• Becerril C, Pardo A, Montaño M, Ramos C, Ramírez R, Selman M. Acidic fibroblast growth factor induces an antifibrogenic phenotype in human lung fibroblasts. Am J Respir Cell Mol Biol. 1999;20:1020–1027.
   PubMed Web of Science ®Google Scholar
• Shibuya M. Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis. 2006;9: 225–230.
   PubMedGoogle Scholar
• Nowak DG, Amin EM, Rennel ES, et al. Regulation of vascular endothelial growth factor (VEGF) splicing from pro-angiogenic to anti-angiogenic isoforms. a novel therapeutic strategy for angiogenesis. J Biol Chem. 2010;285(8):5532–5540.
   PubMed Web of Science ®Google Scholar
• Ebina M, Shimizukawa M, Shibata N, et al. Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2004;169(11):1203–1208.
   PubMed Web of Science ®Google Scholar
• Antoniou KM, Soufla G, Proklou A, et al. Different activity of the biological axis VEGF-Flt-1 (fms-like tyrosine kinase 1) and CXC chemokines between pulmonary sarcoidosis and idiopathic pulmonary fibrosis: a bronchoalveolar lavage study. Clin Dev Immunol. 2009;2009: 537929.
   Google Scholar
• Farkas L, Farkas D, Ask K, et al. VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest. 2009;119:1298–1311.
   PubMed Web of Science ®Google Scholar
• Hamada N, Kuwano K, Yamada M, et al. Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice. J Immunol. 2005;175:1224–1231.
   PubMed Web of Science ®Google Scholar
• Ou XM, Li WC, Liu DS, et al. VEGFR-2 antagonist SU5416 attenuates bleomycin-induced pulmonary fibrosis. Int Immunopharmacol. 2009;9:70–79.
   PubMed Web of Science ®Google Scholar
• Roth GJ, Heckel A, Colbatzky F, et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J Med Chem. 2009;52:4466–4480.
   PubMed Web of Science ®Google Scholar
• Wollin L, Neugebauer J, Ostermann A, et al. Sustained inactivation of human lung fibroblasts by nintedanib. Am J Respir Crit Care Med. 2013;188:A3378.
   Google Scholar
• Andrianifahanana M, Wilkes MC, Gupta SK, et al. Profibrotic TGFb responses require the cooperative action of PDGF and ErbB receptor tyrosine kinases. FASEB J. 2013;27:4444–4454.
   PubMed Web of Science ®Google Scholar
• Li CM, Khosla J, Pagan I, Hoyle P, Sannes PL. TGF-β1 and fibroblast growth factor-1 modify fibroblast growth factor-2 production in type II cells. Am J Physiol Lung Cell Mol Physiol. 2000;279:L1038–L1046.
   PubMed Web of Science ®Google Scholar
• Kucich U, Rosenbloom JC, Herrick DJ, et al. Signaling events required for transforming growth factor-beta stimulation of connective tissue growth factor expression by cultured human lung fibroblasts. Arch Biochem Biophys. 2001;395(1):103–112.
   PubMed Web of Science ®Google Scholar
• Collard HR, Moore BB, Flaherty KR, et al; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007; 176(7):636–643.
   PubMed Web of Science ®Google Scholar
• Kim DS. Acute exacerbations in patients with idiopathic pulmonary fibrosis. Respir Res. 2013;14:86.
   PubMed Web of Science ®Google Scholar
• Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, King TEJr, Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366(21):1968–1977.
   PubMed Web of Science ®Google Scholar
• Costabel U, Inoue Y, Richeldi L, et al. Effect of baseline FVC on decline in lung function with nintedanib: results from the INPULSIS™ trials. Eur Respir J. 2014;44(Suppl 58):1907.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Vancheri C, Failla M, Crimi N, Raghu G. Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology. Eur Respir J. 2010;35(3):496–504.
   PubMed Web of Science ®Google Scholar
• du Bois RM, Nathan SD, Richeldi L, Schwarz MI, Noble PW. Idiopathic pulmonary fibrosis: lung function is a clinically meaningful endpoint for phase III trials. Am J Respir Crit Care Med. 2012;186(8):712–715.
   PubMed Web of Science ®Google Scholar
• Collard HR, Yow E, Richeldi L, Anstrom KJ, Glazer C; IPFnet investigators. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials. Respir Res. 2013;14:73.
   PubMed Web of Science ®Google Scholar
• Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37:356–363.
   PubMed Web of Science ®Google Scholar
• Ley B, Ryerson CJ, Vittinghoff E, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;156:684–691.
   PubMed Web of Science ®Google Scholar
• Margolin S, Margolin B, Margolin D. Removal of interstitial pulmonary fibrosis (asbestos-induced) by oral chemotherapy with pirfenidone. Fed Proc. 1982;41:1550.
   Google Scholar
• Margolin SB, Lefkowitz S. Pirfenidone: a novel pharmacologic agent for prevention and resolution of lung fibrosis. FASEB J. 1994;8:A382.
   Web of Science ®Google Scholar
• Nakazato H, Oku H, Yamane S, Tsuruta Y, Suzuki R. A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor-α at the translational level. Eur J Pharmacol. 2002;446:177–185.
   PubMed Web of Science ®Google Scholar
• Oku H, Nakazato H, Horikawa T, Tsuruta Y, Suzuki R. Pirfenidone suppresses tumor necrosis factor-α, enhances interleukin-10 and protects mice from endotoxic shock. Eur J Pharmacol. 2002;446:167–176.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Misra HP, Rabideau C. Pirfenidone inhibits NADPH-dependent microsomal lipid peroxidation and scavenges hydroxyl radicals. Mol Cell Biochem. 2000;204:119–126.
   PubMed Web of Science ®Google Scholar
• Iyer SN, Wild JS, Schiedt MJ, Hyde DM, Margolin SB, Giri SN. Dietary intake of pirfenidone ameliorates bleomycin-induced lung fibrosis in hamsters. J Lab Clin Med. 1995;125:779–785.
   PubMed Web of Science ®Google Scholar
• Iyer SN, Gurujeyalakshmi G, Giri SN. 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. 1999;291(1):367–373.
   PubMed Web of Science ®Google Scholar
• 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(2 pt 1):L311–L318.
   PubMed Web of Science ®Google Scholar
• 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(1–3):400–408.
   PubMed Web of Science ®Google Scholar
• Taniguchi H, Ebina M, Kondoh Y, et al; Pirfenidone Clinical Study Group in Japan. Pirfenidone Clinical Study Group in Japan. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):821–829.
   PubMed Web of Science ®Google Scholar
• Noble PW, Albera C, Bradford WZ, et al; CAPACITY Study Group. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377:1760–1769.
   PubMed Web of Science ®Google Scholar
• King TE Jr, Bradford WZ, Castro-Bernardini S, et al; ASCEND Study Group. ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–2092.
   PubMed Web of Science ®Google Scholar
• Hunninghake GM. A new hope for idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2142–2143.
   PubMed Web of Science ®Google Scholar
• Lake F. Pirfenidone reduced disease progression in idiopathic pulmonary fibrosis. Ann Intern Med. 2014;161:JC4–JC5.
   Web of Science ®Google Scholar
• Ogura T, Taniguchi H, Azuma A, et al. Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1382–1392.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. CHMP Assessment Report: Esbriet; 2013 [cited December 16, 2010]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002154/WC500103073.pdf. Accessed September 4, 2013.
   Google Scholar