Einsatz antifibrotischer Medikamente bei interstitiellen Lungenerkrankungen

 

 Buy Article Permissions and Reprints

Abstract

The interstitial lung diseases ILDs are a heterogeneous group of diseases that often lead to progressive fibrosis of the lungs with corresponding functional impairment. With nintedanib, a tyrosinkinase inhibitor and angiokinase inhibitor, as well as pirfenidone, which unfolds its effect among other things by inhibiting the transforming growth factor β, there are currently 2 approved antifibrotic drugs. In the rapidly progressing idiopathic pulmonary fibrosis IPF, the antifibrotic drugs nintedanib and pirfenidone have been established and approved in therapy for several years. The initiation of antifibrotic therapy should be carried out early after diagnosis by multidisciplinary discussion (MDD). In systemic scleroderma with lung involvement nintedanib should be used in the case of relevant fibrosis in addition to immunosuppressive therapy. Recently, nintedanib has also become a new option for the treatment of progressive fibrosing ILDs (PF-ILDs). This describes the course of various disease entities such as connective tissue disease associated ILDs (CTD-ILDs), fibrosing hypersensitivity pneumonitis or fibrosing courses of non-IPF idiopathic interstitial pneumonitis (non-IPF IIPs) that have a corresponding fibrose-related worsening of respiratory symptoms, a deterioration of lung-functioning parameters or a disease progression in CT. Although pirfenidone also shows positive signals for this group of patients in some selected studies, its use in PF-ILD is not yet recommended. In particular, gastrointestinal side effects can occur under therapy with antifibrotic drugs and require a long-term close interdisciplinary connection of patients.

Publication History

Article published online:
24 October 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• Literatur

• 1 Wollin L, Wex E, Pautsch A. et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J 2015; 45: 1434-1445 DOI: 10.1183/09031936.00174914.
  CrossrefPubMedGoogle Scholar
• 2 Kwapiszewska G, Gungl A, Wilhelm J. et al. Transcriptome profiling reveals the complexity of pirfenidone effects in idiopathic pulmonary fibrosis. Eur Respir J 2018; 52 DOI: 10.1183/13993003.00564-2018.
  CrossrefPubMedGoogle Scholar
• 3 Raghu G, Anstrom KJ, King TE. et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 2012; 366: 1968-1977 DOI: 10.1056/NEJMoa1113354.
  CrossrefPubMedGoogle Scholar
• 4 Oldham JM, Witt LJ, Adegunsoye A. et al. N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia. BMC Pulm Med 2018; 18: 30 DOI: 10.1186/s12890-018-0599-3.
  CrossrefPubMedGoogle Scholar
• 5 Noble PW, Albera C, Bradford WZ. et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011; 377: 1760-1769 DOI: 10.1016/S0140-6736(11)60405-4.
  CrossrefPubMedGoogle Scholar
• 6 King TE, 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: 2083-2092 DOI: 10.1056/NEJMoa1402582.
  CrossrefPubMedGoogle Scholar
• 7 Richeldi L, Du Bois RM, Raghu G. et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014; 370: 2071-2082 DOI: 10.1056/NEJMoa1402584.
  CrossrefPubMedGoogle Scholar
• 8 Behr J, Günther A, Bonella F. et al. S2k-Leitlinie Idiopathische Lungenfibrose – Update zur medikamentösen Therapie 2017. Pneumologie 2017; 71: 460-474 DOI: 10.1055/s-0043-106160.
  Article in Thieme ConnectPubMedGoogle Scholar
• 9 Albera C, Costabel U, Fagan EA. et al. Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function. Eur Respir J 2016; 48: 843-851 DOI: 10.1183/13993003.01966-2015.
  CrossrefPubMedGoogle Scholar
• 10 Collard HR, Richeldi L, Kim DS. et al. Acute exacerbations in the INPULSIS trials of nintedanib in idiopathic pulmonary fibrosis. Eur Respir J 2017; 49 DOI: 10.1183/13993003.01339-2016.
  CrossrefPubMedGoogle Scholar
• 11 Costabel U, Albera C, Lancaster LH. et al. An Open-Label Study of the Long-Term Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (RECAP). Respiration 2017; 94: 408-415 DOI: 10.1159/000479976.
  CrossrefPubMedGoogle Scholar
• 12 Lancaster L, Albera C, Bradford WZ. et al. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. BMJ Open Respir Res 2016; 3: e000105 DOI: 10.1136/bmjresp-2015-000105.
  CrossrefPubMedGoogle Scholar
• 13 Crestani B, Huggins JT, Kaye M. et al. Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON. The Lancet Respiratory Medicine 2019; 7: 60-68 DOI: 10.1016/S2213-2600(18)30339-4.
  CrossrefPubMedGoogle Scholar
• 14 Richeldi L, Kreuter M, Selman M. et al. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension. Thorax 2018; 73: 581-583 DOI: 10.1136/thoraxjnl-2016-209701.
  CrossrefPubMedGoogle Scholar
• 15 Kreuter M, Picker N, Schwarzkopf L. et al. Epidemiology, healthcare utilization, and related costs among patients with IPF: results from a German claims database analysis. Respir Res 2022; 23: 62 DOI: 10.1186/s12931-022-01976-0.
  CrossrefPubMedGoogle Scholar
• 16 Dempsey TM, Payne S, Sangaralingham L. et al. Adoption of the Antifibrotic Medications Pirfenidone and Nintedanib for Patients with Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc 2021; 18: 1121-1128 DOI: 10.1513/AnnalsATS.202007-901OC.
  CrossrefPubMedGoogle Scholar
• 17 Vancheri C, Kreuter M, Richeldi L. et al. Nintedanib with Add-on Pirfenidone in Idiopathic Pulmonary Fibrosis. Results of the INJOURNEY Trial. Am J Respir Crit Care Med 2018; 197: 356-363 DOI: 10.1164/rccm.201706-1301OC.
  CrossrefPubMedGoogle Scholar
• 18 Cottin V, Brown KK. Interstitial lung disease associated with systemic sclerosis (SSc-ILD). Respir Res 2019; 20: 13 DOI: 10.1186/s12931-019-0980-7.
  CrossrefPubMedGoogle Scholar
• 19 Prasse A, Bonella F, Müller-Ladner U. et al. Therapie der systemischen Sklerose-assoziierten interstitiellen Lungenerkrankung. Z Rheumatol 2020; 79: 294-303 DOI: 10.1007/s00393-019-00724-y.
  CrossrefPubMedGoogle Scholar
• 20 Distler O, Highland KB, Gahlemann M. et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med 2019; 380: 2518-2528 DOI: 10.1056/NEJMoa1903076.
  CrossrefPubMedGoogle Scholar
• 21 Acharya N, Sharma SK, Mishra D. et al. Efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease-a randomised controlled trial. Rheumatol Int 2020; 40: 703-710 DOI: 10.1007/s00296-020-04565-w.
  CrossrefPubMedGoogle Scholar
• 22 Flaherty KR, Wells AU, Cottin V. et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med 2019; 381: 1718-1727 DOI: 10.1056/NEJMoa1908681.
  CrossrefPubMedGoogle Scholar
• 23 Maher TM, Brown KK, Kreuter M. et al. Effects of nintedanib by inclusion criteria for progression of interstitial lung disease. Eur Respir J 2022; 59 DOI: 10.1183/13993003.04587-2020.
  CrossrefPubMedGoogle Scholar
• 24 Wells AU, Flaherty KR, Brown KK. et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases – subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Resp Med 2020; 8: 453-460 DOI: 10.1016/S2213-2600(20)30036-9.
  CrossrefPubMedGoogle Scholar
• 25 Raghu G, Remy-Jardin M, Richeldi L. 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.
  CrossrefPubMedGoogle Scholar
• 26 Maher TM, Corte TJ, Fischer A. et al. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet Respiratory Medicine 2020; 8: 147-157 DOI: 10.1016/S2213-2600(19)30341-8.
  CrossrefPubMedGoogle Scholar
• 27 Behr J, Prasse A, Kreuter M. et al. Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial. The Lancet Respiratory Medicine 2021; 9: 476-486 DOI: 10.1016/S2213-2600(20)30554-3.
  CrossrefPubMedGoogle Scholar
• 28 Wells AU. Pirfenidone in patients with non-IPF progressive fibrotic interstitial lung diseases: expert guidance is urgently needed. The Lancet Respiratory Medicine 2021; 9: 437-438 DOI: 10.1016/S2213-2600(21)00173-9.
  CrossrefPubMedGoogle Scholar
• 29 Ghazipura M, Mammen MJ, Bissell BD. et al. Pirfenidone in Progressive Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. Ann Am Thorac Soc 2022; 19 (06) 1030-1039 DOI: 10.1513/AnnalsATS.202103-342OC.
  CrossrefPubMedGoogle Scholar
• 30 Bendstrup E, Wuyts W, Alfaro T. et al. Nintedanib in Idiopathic Pulmonary Fibrosis: Practical Management Recommendations for Potenzial Adverse Events. Respiration 2019; 97: 173-184 DOI: 10.1159/000495046.
  CrossrefPubMedGoogle Scholar
• 31 Rodríguez-Portal JA. Efficacy and Safety of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis: An Update. Drugs R D 2018; 18: 19-25 DOI: 10.1007/s40268-017-0221-9.
  CrossrefPubMedGoogle Scholar