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Current Respiratory Medicine Reviews

Editor-in-Chief

ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Review Article

Antifibrotic Drugs for COVID-19: From Orphan Drugs to Blockbusters?

Author(s): Leander Corrie*, MD Muzaffar-Ur-Rehman, Latha Kukatil, Devasari Manasa and Adepu Shirisha

Volume 17, Issue 1, 2021

Published on: 04 March, 2021

Page: [8 - 12] Pages: 5

DOI: 10.2174/1573398X17666210304100043

Price: $65

Abstract

Antifibrotic agents are known to treat idiopathic pulmonary fibrosis. The two antifibrotic agents approved and in usage are Pirfenidone and Nintedanib granted by the USFDA in 2014. They are both known to decrease inflammation in the lungs. The fact that COVID-19 has shown to cause inflammation and fibrosis in the lungs frames the theory of their usage in the treatment of the disease by reducing lung scaring and allowing faster discharge of patients with post-COVID complications. The need for them to change their status from orphans to blockbusters has not happened yet due to fewer data and less research available on them as well as various other economic and patient- related factors. Since COVID-19 is widespread and causes many complications of the lungs that are similar to what these two drugs treat. We believe that the status of these drugs could be changed due to an increase in demand for them.

Keywords: Antifibrotic, COVID-19, Pirfenidone, Nintedanib, Orphan drugs, SARS-CoV-2.

Graphical Abstract

[1]
Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8(4): 420-2.
[http://dx.doi.org/10.1016/S2213-2600(20)30076-X] [PMID: 32085846]
[2]
Guzik TJ, Mohiddin SA, Dimarco A, et al. COVID-19 and the cardiovascular system: Implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res 2020; 116(10): 1666-87.
[http://dx.doi.org/10.1093/cvr/cvaa106] [PMID: 32352535]
[3]
Awasthi A, Vishwas S, Corrie L, et al. OUTBREAK of novel corona virus disease (COVID-19): Antecedence and aftermath. Eur J Pharmacol 2020; 884(April): 173381.
[http://dx.doi.org/10.1016/j.ejphar.2020.173381] [PMID: 32721449]
[4]
Wu R, Wang L, Kuo HCD, Shannar A, Peter R, Chou PJ, et al. An update on current therapeutic drugs treating COVID-19. Curr Pharmacol Rep 2020; 6: 56-70.
[5]
Li G, He X, Zhang L, et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J Autoimmun 2020; 112: 102463.
[http://dx.doi.org/10.1016/j.jaut.2020.102463] [PMID: 32303424]
[6]
Wootton SC, Kim DS, Kondoh Y, et al. Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011; 183(12): 1698-702.
[http://dx.doi.org/10.1164/rccm.201010-1752OC] [PMID: 21471095]
[7]
Zhou S. CT features of Coronavirus disease 2019 (COVID-19) Pneumonia in 62 patients in Wuhan, China. 2020; 2020: 1-8.
[8]
Peter M. Pulmonary fibrosis and COVID-19: The potential role for antifibrotic therapy. Lancet Respir Med 2020; 8(8): 807-15.
[9]
Zhang J, Xie B, Hashimoto K. Current status of potential therapeutic candidates for the COVID-19 crisis. In: Brain, Behavior, and Immunity. Academic Press Inc. 2020; 87: pp. 59-73.
[10]
Cerri S, Monari M, Guerrieri A, et al. Real-life comparison of Pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: A 24-month assessment. Respir Med 2019; 159: 105803.
[http://dx.doi.org/10.1016/j.rmed.2019.105803] [PMID: 31670147]
[11]
di Martino E, Provenzani A, Vitulo P, Polidori P. Systematic review and meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the treatment of Idiopathic pulmonary fibrosis. Annal Pharmacotherapy 2020.
[http://dx.doi.org/10.1177/1060028020964451]
[12]
Macías-Barragán J, Sandoval-Rodríguez A, Navarro-Partida J, Armendáriz-Borunda J. The multifaceted role of Pirfenidone and its novel targets. Fibrogenesis Tissue Repair 2010; 3(1): 16.
[http://dx.doi.org/10.1186/1755-1536-3-16] [PMID: 20809935]
[13]
Ruwanpura SM, Thomas BJ, Bardin PG. Pirfenidone: Molecular mechanisms and potential clinical applications in lung disease. Am J Respir Cell Mol Biol 2020; 62(4): 413-22.
[http://dx.doi.org/10.1165/rcmb.2019-0328TR] [PMID: 31967851]
[14]
Bahudhanapati H, Kass DJ. Unwinding the collagen fibrils: Elucidating the mechanism of Pirfenidone and Nintedanib in pulmonary fibrosis. Am J Respir Cell Mol Biol 2017; 57(1): 10-1.
[http://dx.doi.org/10.1165/rcmb.2017-0079ED] [PMID: 28665219]
[15]
Choi YH, Back KO, Kim HJ, Lee SY, Kook KH. Pirfenidone attenuates IL-1β-induced COX-2 and PGE2 production in orbital fibroblasts through suppression of NF-κB activity. Exp Eye Res 2013; 113: 1-8.
[http://dx.doi.org/10.1016/j.exer.2013.05.001] [PMID: 23664858]
[16]
Hisatomi K, Mukae H, Sakamoto N, et al. Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells. BMC Pulm Med 2012; 12: 24.
[http://dx.doi.org/10.1186/1471-2466-12-24] [PMID: 22694981]
[17]
Seifirad S. Pirfenidone: A novel hypothetical treatment for COVID-19. Med Hypotheses 2020; 144: 110005.
[http://dx.doi.org/10.1016/j.mehy.2020.110005] [PMID: 32575019]
[18]
Kim HY, Kim MS, Kim SH, Joen D, Lee K. Protective effects of nintedanib against polyhexamethylene guanidine phosphate-induced lung fibrosis in mice. Molecules 2018; 23(8): E1974.
[http://dx.doi.org/10.3390/molecules23081974] [PMID: 30087305]
[19]
Adderley N, Humphreys CJ, Barnes H, Ley B, Premji ZA, Johannson KA. Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: A systematic review and meta-analysis. Eur Respir J 2020; 56(2): 2000206.
[http://dx.doi.org/10.1183/13993003.00206-2020] [PMID: 32265306]
[20]
Wollin L, Maillet I, Quesniaux V, Holweg A, Ryffel B. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther 2014; 349(2): 209-20.
[http://dx.doi.org/10.1124/jpet.113.208223] [PMID: 24556663]
[21]
Knüppel L, Ishikawa Y, Aichler M, et al. A novel antifibrotic mechanism of nintedanib and pirfenidone. Am J Respir Cell Mol Biol 2017; 57(1): 77-90.
[http://dx.doi.org/10.1165/rcmb.2016-0217OC] [PMID: 28257580]
[22]
King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of Pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014; 370(22): 2083-92.
[http://dx.doi.org/10.1056/NEJMoa1402582] [PMID: 24836312]
[23]
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): 2071-82.
[http://dx.doi.org/10.1056/NEJMoa1402584] [PMID: 24836310]
[24]
Noble PW, Albera C, Bradford WZ, et al. Pirfenidone for idiopathic pulmonary fibrosis: Analysis of pooled data from three multinational phase 3 trials. Eur Respir J 2016; 47(1): 243-53. [Internet]
[http://dx.doi.org/10.1183/13993003.00026-2015] [PMID: 26647432]
[25]
Dhooria S, Agarwal R, Dhar R, Jindal A, Madan K, Aggarwal AN. Consensus statement for the diagnosis and treatment of idiopathic pulmonary fibrosis in resource constrained settings consensus statement for the diagnosis and treatment of idiopathic pulmonary fibrosis in resource constrained settings. 2018.
[26]
Bargagli E, Piccioli C, Rosi E, et al. Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience in an Italian referral centre. Pulmonology 2019; 25(3): 149-53.
[http://dx.doi.org/10.1016/j.pulmoe.2018.06.003] [PMID: 30236523]
[27]
Moodley YP, Scaffidi AK, Misso NL, et al. Fibroblasts isolated from normal lungs and those with idiopathic pulmonary fibrosis differ in interleukin-6/gp130-mediated cell signaling and proliferation. Am J Pathol 2003; 163(1): 345-54.
[http://dx.doi.org/10.1016/S0002-9440(10)63658-9] [PMID: 12819039]
[28]
Hadda V, Guleria R. Antifibrotic drugs for idiopathic pulmonary fibrosis: What we should know? Indian J Med Res 2020; 152(3): 177-80.
[http://dx.doi.org/10.4103/ijmr.IJMR_90_20] [PMID: 33107479]
[29]
Li Y, Li H, Liu S, et al. Pirfenidone ameliorates lipopolysaccharide-induced pulmonary inflammation and fibrosis by blocking NLRP3 inflammasome activation. Mol Immunol 2018; 99(87): 134-44.
[http://dx.doi.org/10.1016/j.molimm.2018.05.003] [PMID: 29783158]
[30]
Sathiyamoorthy G, Sehgal S, Ashton RW. Pirfenidone and Nintedanib for treatment of idiopathic pulmonary fibrosis. South Med J 2017; 110(6): 393-8.
[http://dx.doi.org/10.14423/SMJ.0000000000000655] [PMID: 28575896]
[31]
Trawinska MA, Rupesinghe RD, Hart SP. Patient considerations and drug selection in the treatment of idiopathic pulmonary fibrosis. Ther Clin Risk Manag 2016; 12: 563-74.
[PMID: 27114711]
[32]
Borthwick LA. The IL-1 cytokine family and its role in inflammation and fibrosis in the lung. Semin Immunopathol 2016; 38(4): 517-34.
[http://dx.doi.org/10.1007/s00281-016-0559-z] [PMID: 27001429]
[33]
Gad ES, Salama AAA, El-Shafie MF, Arafa HMM, Abdelsalam RM, Khattab M. The anti-fibrotic and anti-inflammatory potential of bone marrow-derived mesenchymal stem cells and nintedanib in bleomycin-induced lung fibrosis in rats. Inflammation 2020; 43(1): 123-34.
[http://dx.doi.org/10.1007/s10753-019-01101-2] [PMID: 31646446]
[34]
Chen WC, Chen NJ, Chen HP, et al. Nintedanib reduces neutrophil chemotaxis via activating GRK2 in bleomycin-induced pulmonary fibrosis. Int J Mol Sci 2020; 21(13): 1-16.
[http://dx.doi.org/10.3390/ijms21134735] [PMID: 32630825]
[35]
Li T, Guo L, Chen Z, et al. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis. Sci Rep 2016; 6(September): 33226.
[http://dx.doi.org/10.1038/srep33226] [PMID: 27615411]
[36]
Yanagihara T, Suzuki K, Egashira A, et al. Nintedanib and intensive immunosuppressive therapy to treat rapidly progressive interstitial lung disease presenting anti-ARS antibodies. Respir Med Case Rep 2020; 31: 101272.
[http://dx.doi.org/10.1016/j.rmcr.2020.101272] [PMID: 33163354]
[37]
Furuya K, Sakamoto S, Shimizu H, et al. Pirfenidone for acute exacerbation of idiopathic pulmonary fibrosis: A retrospective study. Respir Med 2017; 126: 93-9.
[http://dx.doi.org/10.1016/j.rmed.2017.03.026] [PMID: 28427556]
[38]
Maher TM, Stowasser S, Nishioka Y, et al. Biomarkers of extracellular matrix turnover in patients with idiopathic pulmonary fibrosis given nintedanib (INMARK study): A randomised, placebo- controlled study. Lancet Respir Med 2019; 7(9): 771-9.
[http://dx.doi.org/10.1016/S2213-2600(19)30255-3] [PMID: 31326319]
[39]
Stahnke T, Kowtharapu BS, Stachs O, et al. Suppression of TGF-β pathway by Pirfenidone decreases extracellular matrix deposition in ocular fibroblasts in vitro. PLoS One 2017; 12(2): e0172592.
[http://dx.doi.org/10.1371/journal.pone.0172592] [PMID: 28231275]
[40]
Lin X, Wen J, Liu R, Gao W, Qu B, Yu M. Nintedanib inhibits TGF-β-induced myofibroblast transdifferentiation in human Tenon’s fibroblasts. Mol Vis 2018; 24: 789-800.
[PMID: 30636861]
[41]
Kurimoto R, Ebata T, Iwasawa S, et al. Pirfenidone may revert the epithelial-to-mesenchymal transition in human lung adenocarcinoma. Oncol Lett 2017; 14(1): 944-50.
[http://dx.doi.org/10.3892/ol.2017.6188] [PMID: 28693256]
[42]
Ihara H, Mitsuishi Y, Kato M, et al. Nintedanib inhibits epithelial-mesenchymal transition in A549 alveolar epithelial cells through regulation of the TGF-β/Smad pathway. Respir Investig 2020; 58(4): 275-84.
[http://dx.doi.org/10.1016/j.resinv.2020.01.003] [PMID: 32359980]

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