Przyszłość leczenia farmakologicznego idiopatycznego włóknienia płuc
Słowa kluczowe:
idiopatyczne włóknienie płuc, IPF, farmakoterapia, patogenezaStreszczenie
Idiopatyczne włóknienie płuc(idiopathic pulmonary fibrosis, IPF) to przewlekłe, postępujące śródmiąższowe zapalenie prowadzące do ubytku czynnego miąższu płuca i rozwinięcia niewydolności oddechowej. Średnia długość życia nieleczonego chorego od momentu zdiagnozowania wynosi 3 do 5 lat. Do rozwoju IPF przyczyniają się powtarzające mikrouszkodzenia nabłonka pęcherzyków płucnych i współistniejąca podatność genetyczna prowadząca do nieprawidłowej naprawy tkanki i włóknienia płuc które z czasem powoduje niewydolność oddechową. Obecnie stosowane leczenie farmakologiczne obejmuje tylko dwa leki: pirfenidon i nintedanib które spowalniają progresję choroby. Wyniki terapii nie są satysfakcjonujące, część pacjentów nie odpowiada na leczenie. Postęp wiedzy w zakresie patogenezy choroby dostarcza nowych potencjalnych punktów uchwytu dla terapii IPF. Do leków analizowanych w badaniach klinicznych fazy 2 i 3 należą: rekombinowana ludzka pentraksyna 2 o plejotropowym wpływie na ludzki układ odpornościowy i proces naprawy uszkodzonych tkanek, ludzkie przeciwciało monoklonalne pamrevlumab hamujące aktywność czynnika wzrostu tkanki łącznej odpowiadającego za proces włóknienia, agoniści i antagoniści receptorów związanych z białkiem G regulujących procesy regeneracji i włóknienia, inhibitor profibrotycznej galektyny 3, inhibitor fosfodiesterazy 4B wykazujący właściwości przeciwzapalne i hamujący włóknienie a także inhibitory autotaksyny i stosowana już wcześniej N-acetylocysteina. Poznanie genetycznych czynników wpływających na rozwój choroby, przebieg i odpowiedź na leczenie- genu MUC5B, TOLLIP, genów związane z telomerami i innych umożliwi w przyszłości spersonalizowanie leczenia i dostosowanie terapii do genotypu danego chorego.
Rozdziały
-
Przyszłość leczenia farmakologicznego idiopatycznego włóknienia płuc
Bibliografia
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(6):788-824. doi:10.1164/rccm.2009-040GL
Spagnolo P, Kropski JA, Jones MG, et al. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development. Pharmacol Ther. 2021;222. doi:10.1016/j.pharmthera.2020.107798
Glass DS, Grossfeld D, Renna HA, et al. Idiopathic pulmonary fibrosis: Current and future treatment. Clinical Respiratory Journal. 2022;16(2):84-96. doi:10.1111/crj.13466
Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: Pathogenesis and management. Respir Res. 2018;19(1). doi:10.1186/s12931-018-0730-2
Cottin V, Bonniaud P, Cadranel J, et al. French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis – 2021 update. Full-length version. Respir Med Res. 2023;83:100948. doi:10.1016/j.resmer.2022.100948
Yang I v., Fingerlin TE, Evans CM, Schwarz MI, Schwartz DA. MUC5B and Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2015;12(Supplement 2):S193-S199. doi:10.1513/AnnalsATS.201503-110AW
Okuda K, Chen G, Subramani DB, et al. Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways. Am J Respir Crit Care Med. 2019;199(6):715-727. doi:10.1164/rccm.201804-0734OC
Faruque M, Wanschers M, Ligtenberg AJ, Laine ML, Bikker FJ. A review on the role of salivary MUC5B in oral health. J Oral Biosci. 2022;64(4):392-399. doi:10.1016/j.job.2022.09.005
WICKSTRÖM C, DAVIES JR, ERIKSEN G v., VEERMAN ECI, CARLSTEDT I. MUC5B is a major gel-forming, oligomeric mucin from human salivary gland, respiratory tract and endocervix: identification of glycoforms and C-terminal cleavage. Biochemical Journal. 1998;334(3):685-693. doi:10.1042/bj3340685
Hunninghake GM, Hatabu H, Okajima Y, et al. MUC5B Promoter Polymorphism and Interstitial Lung Abnormalities. New England Journal of Medicine. 2013;368(23):2192-2200. doi:10.1056/NEJMoa1216076
Peljto AL, Zhang Y, Fingerlin TE, et al. Association Between the MUC5B Promoter Polymorphism and Survival in Patients With Idiopathic Pulmonary Fibrosis. JAMA. 2013;309(21):2232. doi:10.1001/jama.2013.5827
Ley B, Collard H. Epidemiology of idiopathic pulmonary fibrosis. Clin Epidemiol. Published online November 2013:483. doi:10.2147/CLEP.S54815
Newton CA, Oldham JM, Ley B, et al. Telomere length and genetic variant associations with interstitial lung disease progression and survival. European Respiratory Journal. 2019;53(4):1801641. doi:10.1183/13993003.01641-2018
Newton CA, Batra K, Torrealba J, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. European Respiratory Journal. 2016;48(6):1710-1720. doi:10.1183/13993003.00308-2016
Oldham JM, Ma SF, Martinez FJ, et al. TOLLIP , MUC5B , and the Response to N -Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2015;192(12):1475-1482. doi:10.1164/rccm.201505-1010OC
Klingberg F, Hinz B, White ES. The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol. 2013;229(2):298-309. doi:10.1002/path.4104
Lv Q, Wang J, Xu C, Huang X, Ruan Z, Dai Y. Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways. Molecular Medicine. 2020;26(1):49. doi:10.1186/s10020-020-00173-3
Guo J, Yang Z, Jia Q, Bo C, Shao H, Zhang Z. Pirfenidone inhibits epithelial-mesenchymal transition and pulmonary fibrosis in the rat silicosis model. Toxicol Lett. 2019;300:59-66. doi:10.1016/j.toxlet.2018.10.019
Conte E, Gili E, Fagone E, Fruciano M, Iemmolo M, Vancheri C. Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts. European Journal of Pharmaceutical Sciences. 2014;58:13-19. doi:10.1016/j.ejps.2014.02.014
King TE, Bradford WZ, Castro-Bernardini S, et al. A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. New England Journal of Medicine. 2014;370(22):2083-2092. doi:10.1056/NEJMoa1402582
Vancheri C, du Bois RM. A progression-free end-point for idiopathic pulmonary fibrosis trials: lessons from cancer. European Respiratory Journal. 2013;41(2):262-269. doi:10.1183/09031936.00115112
Nathan SD, Costabel U, Albera C, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment. Respir Med. 2019;153:44-51. doi:10.1016/j.rmed.2019.04.016
Glassberg MK, Wijsenbeek MS, Gilberg F, Petzinger U, Kirchgaessler KU, Albera C. Effect of pirfenidone on breathlessness in patients with idiopathic pulmonary fibrosis. European Respiratory Journal. 2019;54(3):1900399. doi:10.1183/13993003.00399-2019
Nathan SD, Costabel U, Glaspole I, et al. Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis. Chest. 2019;155(4):712-719. doi:10.1016/j.chest.2018.11.008
Ley B, Swigris J, Day B mo, et al. Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2017;196(6):756-761. doi:10.1164/rccm.201701-0091OC
Vancheri C, du Bois RM. A progression-free end-point for idiopathic pulmonary fibrosis trials: lessons from cancer. European Respiratory Journal. 2013;41(2):262-269. doi:10.1183/09031936.00115112
Fisher M, Nathan SD, Hill C, et al. Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis. J Manag Care Spec Pharm. 2017;23(3-b Suppl):S17-S24. doi:10.18553/jmcp.2017.23.3-b.s17
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. Journal of Pharmacology and Experimental Therapeutics. 2014;349(2):209-220. doi:10.1124/jpet.113.208223
Costabel U, Inoue Y, Richeldi L, et al. Efficacy of Nintedanib in Idiopathic Pulmonary Fibrosis across Prespecified Subgroups in INPULSIS. Am J Respir Crit Care Med. 2016;193(2):178-185. doi:10.1164/rccm.201503-0562OC
Richeldi L, du Bois RM, Raghu G, et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. New England Journal of Medicine. 2014;370(22):2071-2082. doi:10.1056/NEJMoa1402584
Somogyi V, Chaudhuri N, Torrisi SE, Kahn N, Müller V, Kreuter M. The therapy of idiopathic pulmonary fibrosis: what is next? European Respiratory Review. 2019;28(153):190021. doi:10.1183/16000617.0021-2019
Shumar JN, Chandel A, King CS. Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD. J Clin Med. 2021;10(11):2285. doi:10.3390/jcm10112285
Pilling D, Gomer RH. The Development of Serum Amyloid P as a Possible Therapeutic. Front Immunol. 2018;9. doi:10.3389/fimmu.2018.02328
Cox N, Pilling D, Gomer RH. Serum amyloid P: a systemic regulator of the innate immune response. J Leukoc Biol. 2014;96(5):739-743. doi:10.1189/jlb.1MR0114-068R
Murray LA, Chen Q, Kramer MS, et al. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. Int J Biochem Cell Biol. 2011;43(1):154-162. doi:10.1016/j.biocel.2010.10.013
van den Blink B, Dillingh MR, Ginns LC, et al. Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy. European Respiratory Journal. 2016;47(3):889-897. doi:10.1183/13993003.00850-2015
Raghu G, van den Blink B, Hamblin MJ, 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(22):2299. doi:10.1001/jama.2018.6129
Raghu G, van den Blink B, Hamblin MJ, et al. Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study. Lancet Respir Med. 2019;7(8):657-664. doi:10.1016/S2213-2600(19)30172-9
Raghu G, Hamblin MJ, Brown AW, et al. Long-term evaluation of the safety and efficacy of recombinant human pentraxin-2 (rhPTX-2) in patients with idiopathic pulmonary fibrosis (IPF): an open-label extension study. Respir Res. 2022;23(1):129. doi:10.1186/s12931-022-02047-0
NCT04552899.
Kaplon H, Muralidharan M, Schneider Z, Reichert JM. Antibodies to watch in 2020. MAbs. 2020;12(1). doi:10.1080/19420862.2019.1703531
Effendi WI, Nagano T. Connective Tissue Growth Factor in Idiopathic Pulmonary Fibrosis: Breaking the Bridge. Int J Mol Sci. 2022;23(11):6064. doi:10.3390/ijms23116064
Raghu G, Scholand MB, de Andrade J, et al. FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary fibrosis. European Respiratory Journal. 2016;47(5):1481-1491. doi:10.1183/13993003.01030-2015
Richeldi L, Fernández Pérez ER, Costabel U, 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(1):25-33. doi:10.1016/S2213-2600(19)30262-0
NCT03955146.
Pamrevlumab Overview. Accessed February 13, 2023. https://www.creativebiolabs.net/pamrevlumab-overview.htm
Grundmann M, Bender E, Schamberger J, Eitner F. Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators. Int J Mol Sci. 2021;22(4):1763. doi:10.3390/ijms22041763
Gagnon L, Leduc M, Thibodeau JF, et al. A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors. Am J Pathol. 2018;188(5):1132-1148. doi:10.1016/j.ajpath.2018.01.009
Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T, Narumiya S. A GPR40 Agonist GW9508 Suppresses CCL5, CCL17, and CXCL10 Induction in Keratinocytes and Attenuates Cutaneous Immune Inflammation. Journal of Investigative Dermatology. 2011;131(8):1660-1667. doi:10.1038/jid.2011.123
Lovgren AK, Kovacs JJ, Xie T, et al. β-Arrestin Deficiency Protects Against Pulmonary Fibrosis in Mice and Prevents Fibroblast Invasion of Extracellular Matrix. Sci Transl Med. 2011;3(74). doi:10.1126/scitranslmed.3001564
Khalil N, Manganas H, Ryerson CJ, et al. Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis. European Respiratory Journal. 2019;53(3):1800663. doi:10.1183/13993003.00663-2018
Strambu IR, Seemayer CA, Fagard LMCA, et al. GLPG1205 for idiopathic pulmonary fibrosis: a Phase 2 randomised placebo-controlled trial. European Respiratory Journal. Published online November 3, 2022:2201794. doi:10.1183/13993003.01794-2022
Delaine T, Collins P, MacKinnon A, et al. Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition. ChemBioChem. 2016;17(18):1759-1770. doi:10.1002/cbic.201600285
Li L cheng, Li J, Gao J. Functions of Galectin-3 and Its Role in Fibrotic Diseases. Journal of Pharmacology and Experimental Therapeutics. 2014;351(2):336-343. doi:10.1124/jpet.114.218370
Schramm F, Schaefer L, Wygrecka M. EGFR Signaling in Lung Fibrosis. Cells. 2022;11(6):986. doi:10.3390/cells11060986
Cao H, Wang C, Chen X, et al. Inhibition of Wnt/β-catenin signaling suppresses myofibroblast differentiation of lung resident mesenchymal stem cells and pulmonary fibrosis. Sci Rep. 2018;8(1):13644. doi:10.1038/s41598-018-28968-9
Henderson WR, Chi EY, Ye X, et al. Inhibition of Wnt/β-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proceedings of the National Academy of Sciences. 2010;107(32):14309-14314. doi:10.1073/pnas.1001520107
Hirani N, MacKinnon AC, Nicol L, et al. Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis. European Respiratory Journal. 2021;57(5):2002559. doi:10.1183/13993003.02559-2020
NCT03832946.
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, et al. Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis. New England Journal of Medicine. 2022;386(23):2178-2187. doi:10.1056/NEJMoa2201737
NCT05321069.
Platé M, Guillotin D, Chambers RC. The promise of mTOR as a therapeutic target pathway in idiopathic pulmonary fibrosis. European Respiratory Review. 2020;29(157):200269. doi:10.1183/16000617.0269-2020
Mercer PF, Woodcock H v, Eley JD, et al. Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF. Thorax. 2016;71(8):701-711. doi:10.1136/thoraxjnl-2015-207429
NCT01725139.
Jia Y, Li Y, Xu XD, Tian Y, Shang H. Design and Development of Autotaxin Inhibitors. Pharmaceuticals. 2021;14(11):1203. doi:10.3390/ph14111203
Oikonomou N, Mouratis MA, Tzouvelekis A, et al. Pulmonary Autotaxin Expression Contributes to the Pathogenesis of Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2012;47(5):566-574. doi:10.1165/rcmb.2012-0004OC
Maher TM, van der Aar EM, van de Steen O, 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(8):627-635. doi:10.1016/S2213-2600(18)30181-4
Maher TM, Kreuter M, Lederer DJ, et al. Rationale, design and objectives of two phase III, randomised, placebo-controlled studies of GLPG1690, a novel autotaxin inhibitor, in idiopathic pulmonary fibrosis (ISABELA 1 and 2). BMJ Open Respir Res. 2019;6(1):e000422. doi:10.1136/bmjresp-2019-000422
NCT03733444.
NCT03711162.
Gilead. Accessed February 16, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2021/2/galapagos-and-gilead-discontinue-isabela-phase-3-trials-in-ipf
NCT03830125.
NCT04138849.
NCT05483907.
NCT05373914.
Podolanczuk AJ, Kim JS, Cooper CB, et al. Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial. BMC Pulm Med. 2022;22(1):475. doi:10.1186/s12890-022-02281-8
Opublikowane
18 czerwca 2023
Prawa autorskie (c) 2023 Witold Kimla; Daniel Kiełtyka, Paweł Łajczak, Natalia Hajok
Licencja
Utwór dostępny jest na licencji Creative Commons Uznanie autorstwa – Użycie niekomercyjne – Bez utworów zależnych 4.0 Międzynarodowe.
