Pharmacological treatment in Idiopathic Pulmonary Fibrosis: current issues and future perspectives
Keywords:
idiopathic pulmonary fibrosis, IPF, treatment, therapy, future perspectivesAbstract
Idiopathic pulmonary fibrosis (IPF) represents a fibrotic interstitial lung disease characterized by uncertain etiology and poor prognosis. Over the years, the path to effective treatments has been marked by a series of advances and setbacks. The introduction of approved antifibrotic drugs, pirfenidone and nintedanib, marked a pivotal moment in the management of IPF. However, despite these advances, these drugs are not curative, although they can slow the natural progression of the disease. The history of drug therapy for IPF goes together with the increased understanding of the pathogenic mechanisms underlying the disease. Based on that, current research efforts continue to explore new therapies, possible personalized treatment strategies, drug combinations, and potential biomarkers for diagnosis and prognosis. In this review, we outline the route that led to the discover of the first effective therapies, ongoing clinical trials, and future directions in the search for more effective treatments.
References
Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Antoniou KM, Bissell BD, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. https://doi.org/10.1164/rccm.202202-0399ST 2022, 205, E18–E47, doi:10.1164/RCCM.202202-0399ST.
Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, et al. Global Incidence and Prevalence of Idiopathic Pulmonary Fibrosis. Respir Res 2021;22:197. doi:10.1186/s12931-021-01791-z.
Ley B, Collard HR, King TE. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2011;183:431-40, doi:10.1164/RCCM.201006-0894CI.
Salonen J, Purokivi M, Bloigu R, Kaarteenaho R. Prognosis and Causes of Death of Patients with Acute Exacerbation of Fibrosing Interstitial Lung Diseases. BMJ Open Respir Res 2020;7. doi:10.1136/bmjresp-2020-000563.
Kim HJ, Perlman D, Tomic R. Natural History of Idiopathic Pulmonary Fibrosis. Respir Med 2015;109:661-70. doi:10.1016/j.rmed.2015.02.002.
Torrisi SE, Ley B, Kreuter M, Wijsenbeek M, Vittinghoff E, Collard HR, et al. The Added Value of Comorbidities in Predicting Survival in Idiopathic Pulmonary Fibrosis: A Multicentre Observational Study. Eur Respir J 2019;53:1801587. doi:10.1183/13993003.01587-2018.
Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of Idiopathic Pulmonary Fibrosis An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2018;198:e44–e68. doi:10.1164/RCCM.201807-1255ST.
Noble PW, Albera C, Bradford WZ, Costabel U, -Glassberg MK, Kardatzke D, et al. Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (CAPACITY): Two Randomised Trials. Lancet 2011;377:1760-69. doi:10.1016/S0140-6736(11)60405-4.
King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med 2014;370:2083-92. doi:10.1056/NEJMOA1402582.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. New Engl J Med 2014;370:2071-82. doi:10.1056/NEJMOA1402584/
Mondoni M, Varone F, Alfano F, Muscato G, Conti C, Saderi L, et al. Predictors of Stability/Improvement of Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis After One Year of Treatment With Nintedanib. Arch Bronconeumol 2023;59:464-66. doi:10.1016/j.arbres.2023.02.010.
Richeldi L, Collard HR, Jones MG. Idiopathic Pulmonary Fibrosis. Lancet 2017;389:1941-52. doi:10.1016/S0140-6736(17)30866-8.
Wynn TA. Integrating Mechanisms of Pulmonary Fibrosis. J Exp Med 2011;208:1339-50. doi:10.1084/JEM.20110551.
Wilson MS, Wynn TA. Pulmonary Fibrosis: Pathogenesis, Etiology and Regulation. Mucosal Immunol 2009;2:103. doi:10.1038/MI.2008.85.
Zaman T, Lee JS. Risk Factors for the Development of Idiopathic Pulmonary Fibrosis: A Review. Curr Pulmonol Rep 2018;7:118-25. doi:10.1007/s13665-018-0210-7.
Spagnolo P, Cottin V. Genetics of Idiopathic Pulmonary Fibrosis: From Mechanistic Pathways to Personalised Medicine. J Med Genet 2017;54:93-9. doi:10.1136/jmedgenet-2016-103973.
Kropski JA, Blackwell TS. Progress in Understanding and Treating Idiopathic Pulmonary Fibrosis. Ann Rev Med 2019;70:211-24. doi:10.1146/annurev-med-041317-102715.
Fernandez IE, Eickelberg O. The Impact of TGF-β on Lung Fibrosis: From Targeting to Biomarkers. Proc Am Thorac Soc 2012;9:111-16. doi:10.1513/PATS.201203-023AW.
Mora AL, Rojas M, Pardo A, Selman M. Emerging Therapies for Idiopathic Pulmonary Fibrosis, a Progressive Age-Related Disease. Nat Rev Drug Discov 2017;16:755-72. doi:10.1038/nrd.2017.170.
McAnulty RJ, Laurent GJ. Pathogenesis of Lung Fibrosis and Potential New Therapeutic Strategies. Exp Nephrol 1995;2:96-107.
Meier-Sydow J, Rust M, Kronenberger H, Thiel C, Amthor M, Riemann H. [Long-Term Follow-up of Lung Function Parameters in Patients with Idiopathic Pulmonary Fibrosis Treated with Prednisone and Azathioprin or d-Penicillamine (Author’s Transl)]. Prax Klin Pneumol 1979;33(Suppl 1):680-88.
Meier-Sydow J, Weiss SM, Buhl R, Rust M, Raghu G. Idiopathic Pulmonary Fibrosis: Current Clinical Concepts and Challenges in Management. Semin Respir Crit Care Med 1994;15:77-96. doi:10.1055/S-2007-1006351/BIB.
Raghu G, Depaso WJ, Cain K, Hammar SP, Wetzel CE, Dreis DF, 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;144:291-96. doi:10.1164/AJRCCM/144.2.291.
Johnson MA, Kwan S, Snell NJC, Nunn AJ, Darbyshire JH, Turner-Warwick, et al. Randomised Controlled Trial Comparing Prednisolone Alone with Cyclophosphamide and Low Dose Prednisolone in Combination in Cryptogenic Fibrosing Alveolitis. Thorax 1989;44:280-88. doi:10.1136/THX.44.4.280.
Douglas WW, Ryu JH, Swensen SJ, Offord KP, Schroeder DR, Caron GM, et al. Colchicine versus Prednisone in the Treatment of Idiopathic Pulmonary Fibrosis. A Randomized Prospective Study. Members of the Lung Study Group. Am J Respir Crit Care Med 1998;158:220-25. doi:10.1164/AJRCCM.158.1.9709089.
Peters SG, McDougall JC, Douglas WW, Coles DT, DeRemee RA. Colchicine in the Treatment of Pulmonary Fibrosis. Chest 1993;103:101-4: doi:10.1378/CHEST.103.1.101.
Rennard SI, Bitterman PB, Ozaki T, Rom WN, Crystal RG. Colchicine Suppresses the Release of Fibroblast Growth Factors from Alveolar Macrophages in Vitro. The Basis of a Possible Therapeutic Approach Ot the Fibrotic Disorders. Am Rev Respir Dis 1988;137:181-5. doi:10.1164/AJRCCM/137.1.181.
King J, Costabel U, Cordier JF, DoPico GA, DuBois RM, Lynch D, et al. 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;161:646-64. doi:10.1164/AJRCCM.161.2.ATS3-00.
Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, et al. High-Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis. N Engl J Med 2005;353:2229-42. doi:10.1056/NEJMOA042976.
Idiopathic Pulmonary Fibrosis Clinical Research -Network; Raghu G, Anstrom KJ, King TE, Lasky JA, Martinez FJ. Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. N Engl J Med 2012;366:1968-77. doi:10.1056/NEJMoa1113354.
Wen FQ, Liu XD, Terasaki Y, Fang QH, Kobayashi T, Abe S, et al. Interferon-γ Reduces Interleukin-4- and Interleukin-13-Augmented Transforming Growth Factor-Β2 Production in Human Bronchial Epithelial Cells by Targeting Smads. Chest 2003;123:372S-373S. doi:10.1016/S0012-3692(15)35217-X.
Ziesche R, Hofbauer E, Wittmann K, Petkov V, Block LH. A Preliminary Study of Long-Term Treatment with Interferon Gamma-1b and Low-Dose Prednisolone in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med 1999;341:1264-9. doi:10.1056/NEJM199910213411703.
Raghu G, Brown KK, Bradford WZ, Starko K, Noble PW, Schwartz DA, et al. A Placebo-Controlled Trial of Interferon Gamma-1b in Patients with Idiopathic Pulmonary Fibrosis. https://doi.org/10.1056/NEJMoa030511 2004, 350, 125–133, doi:10.1056/NEJMOA030511.
King TE, Albera C, Bradford WZ, Costabel U, Hormel P, Lancaster L, et al. Effect of Interferon Gamma-1b on Survival in Patients with Idiopathic Pulmonary Fibrosis (INSPIRE): A Multicentre, Randomised, Placebo-Controlled Trial. Lancet 2009;374:222-8. doi:10.1016/S0140-6736(09)60551-1.
Shi-Wen X, Denton CP, Dashwood MR, Holmes AM, Bou-Gharios G, Pearson JD, et al. Fibroblast Matrix Gene Expression and Connective Tissue Remodeling: Role of Endothelin-1. J Investig Derm 2001;116:417-25. doi:10.1046/J.1523-1747.2001.01256.X.
Park SH, Saleh D, Giaid A, Michel RP. Increased Endothelin-1 in Bleomycin-Induced Pulmonary Fibrosis and the Effect of an Endothelin Receptor Antagonist. Am J Respir Crit Care Med 1997;156:600-8. doi:10.1164/AJRCCM.156.2.9607123.
Ross B, D’Orléans-Juste P, Giaid A. Potential Role of Endothelin-1 in Pulmonary Fibrosis. https://doi.org/10.1165/rcmb.2009-0175TR 2012, 42, 16–20, doi:10.1165/RCMB.2009-0175TR.
Fonseca C, Abraham D, Renzoni EA. Endothelin in Pulmonary Fibrosis. Am J Respir Cell Mol Biol 2011;44:1-10. doi:10.1165/RCMB.2009-0388TR.
King TE, Behr J, Brown KK, Du Bois RM, Lancaster L, De Andrade J.A, et al. BUILD-1: A Randomized Placebo--Controlled Trial of Bosentan in Idiopathic Pulmonary -Fibrosis. https://doi.org/10.1164/rccm.200705-732OC 2012, 177, 75–81, doi:10.1164/RCCM.200705-732OC.
King TE, Brown KK, Raghu G, Du Bois RM, Lynch DA, Martinez F, et al. BUILD-3: A Randomized, Controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis. https://doi.org/10.1164/rccm.201011-1874OC 2012, 184, 92–99, doi:10.1164/RCCM.201011-1874OC.
Raghu G, Behr J, Brown KK, Egan JJ, Kawut SM, Flaherty KR, et al. Treatment of Idiopathic Pulmonary Fibrosis with Ambrisentan: A Parallel, Randomized Trial. Ann Intern Med 2013;158:641-9. doi:10.7326/0003-4819-158-9-201305070-00003.
Raghu G, Million-Rousseau R, Morganti A, Perchenet L, Behr J, Goh N, et al. Macitentan for the Treatment of Idiopathic Pulmonary Fibrosis: The Randomised Controlled MUSIC Trial. Eur Respir J 2013;42:1622-32. doi:10.1183/09031936.00104612.
Ghofrani HA, Wiedemann R, Rose F, Schermuly RT, Olschewski H, Weissmann N, et al. Sildenafil for Treatment of Lung Fibrosis and Pulmonary Hypertension: A Randomised Controlled Trial. Lancet 2002;360:895-900. doi:10.1016/S0140-6736(02)11024-5.
Idiopathic Pulmonary Fibrosis Clinical Research -Network; Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, Hunninghake GW. A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis. N Engl J Med 2010;363:620-8. doi:10.1056/NEJMoa1002110.
Iyer SN, Margolin SB, Hyde DM, Giri SN. Lung Fibrosis Is Ameliorated by Pirfenidone Fed in Diet after the Second Dose in a Three-Dose Bleomycin-Hamster Model. Exp Lung Res 1998;24:119-33. doi:10.3109/01902149809046058.
Molina-Molina M, Machahua-Huamani C, Vicens-Zygmunt V, Llatjós R, Escobar I, Sala-Llinas E, et al. Anti-Fibrotic Effects of Pirfenidone and Rapamycin in Primary IPF Fibroblasts and Human Alveolar Epithelial Cells. BMC Pulm Med 2018;18. doi:10.1186/S12890-018-0626-4.
Jin J, Togo S, Kadoya K, Tulafu M, Namba Y, Iwai M, et al. Pirfenidone Attenuates Lung Fibrotic Fibroblast Responses to Transforming Growth Factor-Β1. Respir Res 2019;20. doi:10.1186/S12931-019-1093-Z.
Raghu G, Johnson, WC, Lockhart D, Mageto Y. 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 1999;159:1061-9. doi:10.1164/AJRCCM.159.4.9805017.
Nagai S, Hamada K, Shigematsu M, Taniyama M, Yamauchi S, Izumi T. Open-Label Compassionate Use One Year-Treatment with Pirfenidone to Patients with Chronic Pulmonary Fibrosis. Internal Med 2002;41:1118-23. doi:10.2169/INTERNALMEDICINE.41.1118.
Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, et al. Double-Blind, Placebo-Controlled Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2005;171:1040-7. doi:10.1164/RCCM.200404-571OC.
Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga MT, et al. Pirfenidone in Idiopathic Pulmonary Fibrosis. Eur Respir J 2010;35:821-9. doi:10.1183/09031936.00005209.
Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (CAPACITY): Two Randomised Trials. Lancet 2011;377:1760-9. doi:10.1016/S0140-6736(11)60405-4.
King TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. New England J Med 2014;370:2083-92. doi:10.1056/NEJMOA1402582.
Noble PW, Albera C, Bradford WZ, Costabel U, Bois RMD, Fagan EA, et al. Pirfenidone for Idiopathic Pulmonary Fibrosis: Analysis of Pooled Data from Three Multinational Phase 3 Trials. Eur Respir J 2016;47:243-53. doi:10.1183/13993003.00026-2015.
Cottin V, Maher T. Long-Term Clinical and Real-World Experience with Pirfenidone in the Treatment of -Idiopathic Pulmonary Fibrosis. Eur Respir Rev 2015;24:58-64. doi:10.1183/09059180.00011514.
Gulati S, Luckhardt TR. Updated Evaluation of the Safety, Efficacy and Tolerability of Pirfenidone in the Treatment of Idiopathic Pulmonary Fibrosis. Drug Healthc Patient Saf 2020;12:85-94. doi:10.2147/DHPS.S224007.
Lancaster LH, de Andrade JA, Zibrak JD, Padilla ML, Albera C, Nathan SD, et al. Pirfenidone Safety and Adverse Event Management in Idiopathic Pulmonary Fibrosis. Eur Respir Rev 2017;26. doi:10.1183/16000617.0057-2017.
Garneau-Tsodikova S, Thannickal V. Protein Kinase Inhibitors in the Treatment of Pulmonary Fibrosis. Curr Med Chem 2008;15:2632-40. doi:10.2174/092986708785908969.
Buchdunger E, O’Reilly T, Wood J. Pharmacology of Imatinib (STI571). Eur J Cancer 2002;38:S28–S36. doi:10.1016/S0959-8049(02)80600-1.
Daniels CE, Lasky JA, Limper AH, Mieras K, Gabor E, Schroeder DR, et al. Imatinib Treatment for Idiopathic Pulmonary Fibrosis: Randomized Placebo-Controlled Trial Results. Am J Respir Crit Care Med 2010;181:604-10. doi:10.1164/RCCM.200906-0964OC.
Chaudhary NI, Roth GJ, Hilberg F, Müller-Quernheim J, Prasse A, Zissel G, et al. Inhibition of PDGF, VEGF and FGF Signalling Attenuates Fibrosis. Eur Respir J 2007;29:976-85. doi:10.1183/09031936.00152106.
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 Pharmac Exper Ther 2014;349:209-20. doi:10.1124/JPET.113.208223.
Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, et al. BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy. Cancer Res 2008;68:4774-82. doi:10.1158/0008-5472.CAN-07-6307.
Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis. N Engl J Med 2011;365:1079-87. doi:10.1056/NEJMOA1103690.
Vancheri C, Kreuter M, Richeldi L, Ryerson CJ, Valeyre D, Grutters JC, et al. Nintedanib with Add-on Pirfenidone in Idiopathic Pulmonary Fibrosis: Results of the INJOURNEY Trial. Am J Respir Crit Care Med 2018;197:356-63. doi:10.1164/RCCM.201706-1301OC.
Https://Www.Clinicaltrials.Gov/.
Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, -Inoue, Y Johkoh T, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022;205:e18-e47. doi:10.1164/rccm.202202-0399ST.
Zulfikar S, Mulholland,S, Adamali H, Barratt SL. -Inhibitors of the Autotaxin-Lysophosphatidic Acid Axis and Their Potential in the Treatment of Interstitial Lung Disease: Current Perspectives. Clin Pharmacol 2020;2:97-108. doi:10.2147/CPAA.S228362.
Tager AM, LaCamera P, Shea BS, Campanella GS, Selman M, Zhao Z, et al. The Lysophosphatidic Acid Receptor LPA1 Links Pulmonary Fibrosis to Lung Injury by Mediating Fibroblast Recruitment and Vascular Leak. Nat Med 2008;14:45-54. doi:10.1038/nm1685.
Oikonomou N, Mouratis MA, Tzouvelekis A, Kaffe E, Valavanis C, Vilaras G, et al. Pulmonary Autotaxin -Expression Contributes to the Pathogenesis of Pulmonary Fibrosis. Am J Respir Cell Mol Biol 2012;47:566-74. doi:10.1165/rcmb.2012-0004OC.
Ninou I, Magkrioti C, Aidinis V. Autotaxin in Pathophysiology and Pulmonary Fibrosis. Front Med (Lausanne) 2018;5. doi:10.3389/fmed.2018.00180.
Maher TM, van der Aar EM, Van de Steen O, Allamassey L, Desrivot J, Dupont S, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GLPG1690, a Novel Autotaxin Inhibitor, to Treat Idiopathic Pulmonary Fibrosis (FLORA): A Phase 2a Randomised Placebo-Controlled Trial. Lancet Respir Med 2018;6:627-35. doi:10.1016/S2213-2600(18)30181-4.
Maher TM, Ford P, Brown KK, Costabel U, Cottin V, Danoff SK, et al. Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis. JAMA 2023;329:1567. doi:10.1001/jama.2023.5355.
Gill MW, Lakshmi S, Cheng PTW, Murphy BJ, Chadwick K, Lehman-McKeeman L, et al. BMS-986278, an LPA1 -Receptor Antagonist for Idiopathic Pulmonary Fibrosis: Preclinical Assessments of Potential Hepatobiliary Toxicity, American Thoracic Society 2019;A5882-A5882.
Corte TJ, Lancaster L, Swigris JJ, Maher TM, Goldin JG, Palmer SM, et al. Phase 2 Trial Design of BMS-986278, a Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist, in Patients with Idiopathic Pulmonary Fibrosis (IPF) or Progressive Fibrotic Interstitial Lung Disease (PF-ILD). BMJ Open Respir Res 2021;8:e001026. doi:10.1136/bmjresp-2021-001026.
Corte TJ, Cottin V, Glassberg MK, Kreuter M, Ogura T, Suda T, et al. BMS-986278, an Oral Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist, for Patients With Idiopathic Pulmonary Fibrosis: Results From a Phase 2 Randomized Trial, American Thoracic Society 2023;A2785-A2785.
Pelaia C, Crimi C, Vatrella A, Tinello C, Terracciano R, Pelaia G. Molecular Targets for Biological Therapies of Severe Asthma. Front Immunol 2020;11. doi:10.3389/fimmu.2020.603312.
Singh S, Kumar NK, Dwiwedi P, Charan J, Kaur R, Sidhu P, et al. Monoclonal Antibodies: A Review. Curr Clin Pharmacol 2018;13:85-99. doi:10.2174/1574884712666170809124728.
Lipson KE, Wong C, Teng Y, Spong S. CTGF Is a Central Mediator of Tissue Remodeling and Fibrosis and Its Inhibition Can Reverse the Process of Fibrosis. Fibrogenesis Tissue Repair 2012;5:S24. doi:10.1186/1755-1536-5-S1-S24.
Richeldi L, Fernández Pérez ER, Costabel U, Albera C, Lederer DJ, Flaherty KR, et al. Pamrevlumab, an Anti-Connective Tissue Growth Factor Therapy, for Idiopathic Pulmonary Fibrosis (PRAISE): A Phase 2, Randomised, Double-Blind, Placebo-Controlled Trial. Lancet Respir Med 2020;8:25-33. doi:10.1016/S2213-2600(19)30262-0.
FibroGen, I. FibroGen Announces Topline Results from Phase 3 ZEPHYRUS-1 Study of Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis.
Pilling D, Galvis-Carvajal E, Karhadkar TR, Cox N, Gomer RH. Monocyte Differentiation and Macrophage Priming Are Regulated Differentially by Pentraxins and Their Ligands. BMC Immunol 2017;18:30. doi:10.1186/s12865-017-0214-z.
Castaño AP, Lin SL, Surowy T, Nowlin BT, Turlapati SA, Patel T, et al. Serum Amyloid P Inhibits Fibrosis Through FcγR-Dependent Monocyte-Macrophage Regulation in Vivo. Sci Transl Med 2009;1. doi:10.1126/scitranslmed.3000111.
Raghu G, van den Blink, B, Hamblin, M.J, Brown, A.W, Golden, J.A, Ho, et al. Effect of Recombinant Human Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis. JAMA 2018;319:2299. doi:10.1001/jama.2018.6129.
Podolanczuk AJ, Richeldi L, Martinez FJ. The Future of Clinical Trials in Idiopathic Pulmonary Fibrosis. JAMA 2023;329:1554. doi:10.1001/jama.2022.23955.
Martinez FJ, Yow E, Flaherty KR, Snyder LD, Durheim MT, Wisniewski SR, et al. Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis. JAMA 2021;325:1841. doi:10.1001/jama.2021.4956.
Raghu G, Ghazipura M, Fleming TR, Aronson KI, Behr J, Brown KK, et al. Meaningful Endpoints for -Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on “Feels, Functions, Survives.” Am J Respir Crit Care Med 2024;209(6):647-69. doi:10.1164/rccm.202312-2213SO.
Worndl E, Hunt EB, Kennedy MP, Henry MT, Plant BJ, Murphy DM. Roflumilast in COPD. Chest 2015;148:e31. doi:10.1378/CHEST.15-0664.
Gooderham M, Papp K. Selective Phosphodiesterase Inhibitors for Psoriasis: Focus on Apremilast. BioDrugs 2015;29:327-39. doi:10.1007/S40259-015-0144-3.
McDowell L, Olin B. Crisaborole: A Novel Nonsteroidal Topical Treatment for Atopic Dermatitis. J Pharm Technol 2019;35:172-78. doi:10.1177/8755122519844507.
Azevedo MF, Faucz FR, Bimpaki E, Horvath A, Levy I, de Alexandre RB, et al. Clinical and Molecular Genetics of the Phosphodiesterases (PDEs). Endocr Rev 2014;35:195-233. doi:10.1210/er.2013-1053.
Pan JB, Hou YH, Zhang GJ. Rolipram Attenuates Bleomycin A5-induced Pulmonary Fibrosis in Rats. Respirology 2009;14:975-82. doi:10.1111/j.1440-1843.2009.01606.x.
Cortijo J, Iranzo A, Milara X, Mata M, Cerdá--Nicolás M, Ruiz-Saurí A, et al. Roflumilast, a Phosphodiesterase 4 Inhibitor, Alleviates Bleomycin-induced Lung Injury. Br J Pharmacol 2009;156:534-44. doi:10.1111/j.1476-5381.2008.00041.x.
Kohyama T, Liu X, Wen FQ, Kobayashi T, Fang Q, Abe S, et al. Cytokines Modulate Cilomilast Response in Lung Fibroblasts. Clinical Immunology 2004;111:297-302. doi:10.1016/j.clim.2004.01.007.
Herrmann FE, Hesslinger C, Wollin L, Nickolaus P. BI 1015550 Is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis. Front Pharmacol 2022;13. doi:10.3389/fphar.2022.838449.
Richeldi L, Azuma A, Cottin V, Kreuter M, Maher TM, Martinez FJ, et al. Design of a Phase III, Double-Blind, Randomised, Placebo-Controlled Trial of BI 1015550 in Patients with Idiopathic Pulmonary Fibrosis (FIBRONEER-IPF). BMJ Open Respir Res 2023;10:e001563. doi:10.1136/bmjresp-2022-001563.
Richeldi L, Azuma A, Cottin V, Hesslinger C, Stowasser S, Valenzuela C, et al. Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis. New England J Med 2022;386:2178-87. doi:10.1056/NEJMoa2201737.
Richeldi L, Azuma A, Cottin V, Hesslinger C, Stowasser S, Valenzuela C, et al. Additive Effect of BI 1015550 and Nintedanib in Patients with IPF. In Proceedings of the 12.01 - Idiopathic interstitial pneumonias; European Respiratory Society, September 4 2022;4606.
Cazzola M, Calzetta L, Rogliani P, Matera MG. The Discovery of Roflumilast for the Treatment of Chronic Obstructive Pulmonary Disease. Expert Opin Drug Discov 2016;11:733-44. doi:10.1080/17460441.2016.1184642.
Lee YJ, Choi SM, Lee YJ, Cho YJ, Yoon H Il; Lee JH, et al. Clinical Impact of Depression and Anxiety in Patients with Idiopathic Pulmonary Fibrosis. PLoS One 2017;12. doi:10.1371/JOURNAL.PONE.0184300.
Edwards GD, Polgar O, Patel S, Barker RE, Walsh JA, Harvey J, et al. Mood Disorder in Idiopathic Pulmonary Fibrosis: Response to Pulmonary Rehabilitation. ERJ Open Res 2023;9. doi:10.1183/23120541.00585-2022.
Torrisi SE, Vancheri A, Pavone M, Sambataro G, Palmucci S, Vancheri C. Comorbidities of IPF: How Do They Impact on Prognosis. Pulm Pharmacol Ther 2018;53:6-11. doi:10.1016/J.PUPT.2018.09.003.
Nathan SD, King CS. Treatment of Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis: Shortfall in Efficacy or Trial Design? Drug Des Devel Ther 2014;8:875. doi:10.2147/DDDT.S64907.
Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF. Prevalence and Outcomes of Pulmonary Arterial Hypertension in Advanced Idiopathic Pulmonary Fibrosis. Chest 2006;129:746-52. doi:10.1378/CHEST.129.3.746.
Nikkho SM, Richter MJ, Shen E, Abman SH, Antoniou K, Chung J, et al. Clinical Significance of Pulmonary Hypertension in Interstitial Lung Disease: A Consensus Statement from the Pulmonary Vascular Research Institute’s Innovative Drug Development Initiative-Group 3 Pulmonary Hypertension. Pulm Circ 2022;12. doi:10.1002/PUL2.12127.
Behr J, Nathan SD, Wuyts WA, Mogulkoc Bishop N, Bouros DE, Antoniou K, et al. Efficacy and Safety of Sildenafil Added to Pirfenidone in Patients with Advanced Idiopathic Pulmonary Fibrosis and Risk of Pulmonary Hypertension: A Double-Blind, Randomised, Placebo-Controlled, Phase 2b Trial. Lancet Respir Med 2021;9:85-95. doi:10.1016/S2213-2600(20)30356-8.
Nathan SD, Flaherty KR, Glassberg MK, Raghu G, Swigris J, Alvarez R, et al. A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis. Chest 2020;158:637-45. doi:10.1016/J.CHEST.2020.02.016.
Nathan SD, Behr J, Collard HR, Cottin V, Hoeper MM, Martinez FJ, et al. Riociguat for Idiopathic Interstitial Pneumonia-Associated Pulmonary Hypertension (RISE-IIP): A Randomised, Placebo-Controlled Phase 2b Study. Lancet Respir Med 2019;7:780-90. doi:10.1016/S2213-2600(19)30250-4.
Waxman A, Restrepo-Jaramillo R, Thenappan T, Ravichandran A, Engel P, Bajwa A, et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N Engl J Med 2021;384:325-34. doi:10.1056/NEJMOA2008470.
Whittle BJ, Silverstein AM, Mottola DM, Clapp LH. Binding and Activity of the Prostacyclin Receptor (IP) Agonists, Treprostinil and Iloprost, at Human Prostanoid Receptors: Treprostinil Is a Potent DP1 and EP2 Agonist. Biochem Pharmacol 2012;84:68-75. doi:10.1016/J.BCP.2012.03.012.
Nathan SD, Waxman A, Rajagopal S, Case A, Johri S, DuBrock H, et al. Inhaled Treprostinil and Forced Vital Capacity in Patients with Interstitial Lung Disease and Associated Pulmonary Hypertension: A Post-Hoc Analysis of the INCREASE Study. Lancet Respir Med 2021;9:1266-74. doi:10.1016/S2213-2600(21)00165-X.
Nathan SD, Behr J, Cottin V, Lancaster L, Smith P, Deng CQ, et al. Study Design and Rationale for the TETON Phase 3, Randomised, Controlled Clinical Trials of Inhaled Treprostinil in the Treatment of Idiopathic Pulmonary Fibrosis. BMJ Open Respir Res 2022;9. doi:10.1136/BMJRESP-2022-001310.
Müller S, Zeidler C, Ständer S. Chronic Prurigo Including Prurigo Nodularis: New Insights and Treatments. Am J Clin Dermatol 2023;25(1):15-33. doi:10.1007/S40257-023-00818-Z.
Kitko CL, Arora M, Defilipp Z, Zaid MA, Di Stasi A, Radojcic V, et al. Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study. J Clin Oncol 2023;41:1864-75. doi:10.1200/JCO.22.00958.
Oldham JM, Ma SF, Martinez FJ, Anstrom KJ, Raghu G, Schwartz DA, et al. TOLLIP, MUC5B, and the Response to N-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2015;192:1475-82. doi:10.1164/RCCM.201505-1010OC.
Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, et al. Genetic Variants Associated with Idiopathic -Pulmonary Fibrosis Susceptibility and Mortality: A Genome-Wide Association Study. Lancet Respir Med 2013;1:309-17. doi:10.1016/S2213-2600(13)70045-6.
Trujillo G, Meneghin A, Flaherty KR, Sholl LM, Myers JL, Kazerooni EA, et al. TLR9 Differentiates Rapidly from Slowly Progressing Forms of Idiopathic Pulmonary Fibrosis. Sci Transl Med 2010;2. doi:10.1126/SCITRANSLMED.3001510.
Russell AM, Adamali H, Molyneaux PL, Lukey PT, Marshall RP, Renzoni EA, et al. Daily Home Spirometry: An Effective Tool for Detecting Progression in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2016;194:989-97. doi:10.1164/RCCM.201511-2152OC.
Zhao C, Yin Y, Zhu C, Zhu M, Ji T, Li Z, et al. Drug Therapies for Treatment of Idiopathic Pulmonary Fibrosis: A Systematic Review, Bayesian Network Meta-Analysis, and Cost-Effectiveness Analysis. EClinical Medicine 2023;61. doi:10.1016/J.ECLINM.2023.102071.
Raghu G, Rochwerg B, Zhang Y, Garcia CAC, Azuma A, Behr J, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med 2015;192:e3-e19. doi:10.1164/RCCM.201506-1063ST.
Lancaster LH, de Andrade JA, Zibrak JD, Padilla ML, Albera C, Nathan SD, et al. Pirfenidone Safety and Adverse Event Management in Idiopathic Pulmonary Fibrosis. Eur Respir Rev 2017;26. doi:10.1183/16000617.0057-2017.
West A, Chaudhuri N, Barczyk A, Wilsher ML, Hopkins P, Glaspole I, et al. Inhaled Pirfenidone Solution (AP01) for IPF: A Randomised, Open-Label, Dose-Response Trial. Thorax 2023;78(9):882-9. doi:10.1136/thorax-2022-219391.
Vigeland CL, Hughes AH, Horton MR. Etiology and Treatment of Cough in Idiopathic Pulmonary Fibrosis. Respir Med 2017;123:98-104. doi:10.1016/j.rmed.2016.12.016.
Biondini D, Balestro E, Sverzellati N, Cocconcelli E, Bernardinello N, Ryerson CJ, et al. Acute Exacerbations of Idiopathic Pulmonary Fibrosis (AE-IPF): An Overview of Current and Future Therapeutic Strategies. Expert Rev Respir Med 2020;14:405-14. doi:10.1080/17476348.2020.1724096.
Janowiak P, Szymanowska-Narloch A, Siemi-ska A. IPF Respiratory Symptoms Management — Current Evidence. Front Med (Lausanne) 2022;9. doi:10.3389/fmed.2022.917973.
Kondoh Y, Cottin V, Brown KK. Recent Lessons Learned in the Management of Acute Exacerbation of Idiopathic Pulmonary Fibrosis. Eur Respir Rev 2017;26:170050. doi:10.1183/16000617.0050-2017.
Key AL, Holt K, Hamilton A, Smith JA, Earis JE. Objective Cough Frequency in Idiopathic Pulmonary Fibrosis. Cough 2010;6. doi:10.1186/1745-9974-6-4.
Hope-Gill BDM, Hilldrup S, Davies C, Newton RP, Harrison NK. A Study of the Cough Reflex in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2003;168:995-1002. doi:10.1164/RCCM.200304-597OC.
Martinez FJ, Afzal AS, Smith JA, Ford AP, Li JJ, Li Y, et al. Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial. Pulm Ther 2021;7:471. doi:10.1007/S41030-021-00162-9.
Visca D, Beghè B, Fabbri LM, Papi A, Spanevello A. Management of Chronic Refractory Cough in Adults. Eur J Intern Med 2020;81. doi:10.1016/J.EJIM.2020.09.008.
Maher TM, Forbes W, Bortey E, Sciascia T. An Interim Analysis of a Phase 2 Trial Evaluating Oral Nalbuphine Extended Release for Treating Chronic Cough in Idiopathic Pulmonary Fibrosis. Eur Respir J 2022;60:4404. doi:10.1183/13993003.CONGRESS-2022.4404.
Churg A, Müller NL, Silva CIS, Wright JL. Acute Exacerbation (Acute Lung Injury of Unknown Cause) in UIP and Other Forms of Fibrotic Interstitial Pneumonias. Am J Surg Pathol 2007;31:277-84. doi:10.1097/01.PAS.0000213341.70852.9D.
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