" /> 【特集】特発性間質性肺炎の診療の現状と将来展望■特発性肺線維症に対する抗線維化薬の使い方■林　宏紀，ほか |
呼吸臨床

【特集】特発性間質性肺炎の診療の現状と将来展望

企画：小倉高志


　最近，特発性間質性肺炎(IIPs)は次の点で注目されています。①IIPsの中でも頻度の高く，難治性といわれている特発性肺線維症（IPF）に対する２つの抗線維化薬（ピルフェニドン，ニンテダティブ）が出現して，IIPsならIPFか，それ以外のnon-IPFかの鑑別がすることが治療選択や予後に大きく影響を与えるようになりました。②無症状で潜在性な間質性肺炎患者が増加している可能性が示唆されています。すなわち，いくつもの成人病のコホート，肺癌やCOPDのCT検診でInterstitial Lung Abnormalities(ILA)を８〜10％に認めて，その一部はIPFに進展する可能性あるという報告がされています。呼吸器内科医すべてが，IIPsの診断，治療にかかわる機会が多くなることが予想されます。今回，IIPs診療の第一線で治療にあたっている専門家にIIPsの最近の診断と治療について解説していただきます。

特発性肺線維症に対する抗線維化薬の使い方

林　宏紀*，吾妻安良太*

*日本医科大学大学院医学研究科呼吸器内科分野（〒113-0022 東京都文京区千駄木1-1-5）


Idiopathic pulmonary fibrosis and antifibrotic treatments

Hiroki Hayashi*,  Arata Azuma*

*Graduate School of Pulmonary Medicine, Nippon Medical School, Tokyo


Keywords：特発性肺線維症，抗線維化薬，ピルフェニドン，ニンテダニブ／idiopathic pulmonary fibrosis，anti-fibrotic drugs，pirfenidone，nintedanib


呼吸臨床 2018年2巻10号　論文No.e00043
Jpn Open J Respir Med 2018 Vol.2 No.10  Article No.e00043

DOI: 10.24557/kokyurinsho.2.e00043


掲載日：2018年10月20日


©️Hiroki Hayashi, et al. 本論文の複製権，翻訳権，上映権，譲渡権，貸与権，公衆送信権（送信可能化権を含む）は弊社に帰属し，それらの利用ならびに許諾等の管理は弊社が行います。





要旨

　予後不良な疾患である特発性肺線維症に対し，抗線維化薬ピルフェニドン，ニンテダニブが広く使われるようになり，その有効性を示す報告が相次いで示されている。ただし，その2剤の使い分け，開始する時期，併用療法など不明な点が多い。両剤の性格・有害事象を十分理解した上で，患者に説明し，タイミングよく導入することが呼吸器内科医に求められている。

文献

  1. Raghu G, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. New Engl J Med. 2012; 366: 1968-77.
  2. Wiertz IA, et al. Unfavourable outcome of glucocorticoid treatment in suspected idiopathic pulmonary fibrosis. Respirology. 2018; 23: 311-7.
  3. Raghu G, 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: e3-19.
  4. Iyer SN, et al. 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: 367-73.
  5. Macias-Barragan J, et al. The multifaceted role of pirfenidone and its novel targets. Fibrogenesis Tissue Repair. 2010; 3: 16.
  6. Azuma A, 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.
  7. Taniguchi H, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010; 35: 821-9.
  8. Noble PW, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011; 377: 1760-9.
  9. King TE, Jr., et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. New Engl J Med. 2014; 370: 2083-92.
  10. Noble PW, et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J. 2016; 47: 243-53.
  11. Ley B, et al. Pirfenidone reduces respiratory-related hospitalizations in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2017; 196: 756-61.
  12. Azuma A, et al. Exploratory analysis of a phase III trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment. Respir Res. 2011; 12: 143.
  13. Xaubet A, et al. Review of IPF diagnosis and management recommendations in Europe. Sarcoidosis Vasc Diffuse Lung Dis. 2013; 30: 249-61.
  14. Sakamoto S, et al. Efficacy of pirfenidone in patients with advanced-stage idiopathic pulmonary fibrosis. Intern Med. 2013; 52: 2495-501.
  15. Ogura T, et al. All-case post-marketing surveillance of 1371 patients treated with pirfenidone for idiopathic pulmonary fibrosis. Respir Investig. 2015; 53: 232-41.
  16. Lancaster L, 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.
  17. Rubino CM, et al. Effect of food and antacids on the pharmacokinetics of pirfenidone in older healthy adults. Pulm Pharmacol Ther. 2009; 22: 279-85.
  18. Richeldi L, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. New Engl J Med. 2011; 365: 1079-87.
  19. Richeldi L, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. New Engl J Med. 2014; 370: 2071-82.
  20. Crestani B, et al. Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON. Lancet Respir Med. 2018. doi: 10.1016/S2213-2600(18)30339-4.
  21. Ikeda S, et al. Hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis: A single-center experience. Respir Investig. 2017; 55: 51-4.
  22. Albera C, et al. Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function.  Eur Respir J. 2016; 48: 843-51.
  23. Kolb M, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2017; 72: 340-6.
  24. Natsuizaka M, et al. Epidemiologic survey of Japanese patients with idiopathic pulmonary fibrosis and investigation of ethnic differences. Am J Respir Crit Care Med. 2014; 190: 773-9.
  25. Miura Y, et al. Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone. Respir Investig. 2018; 56: 72-9.
  26. Raghu G, 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: 788-824.
  27. Iwata T, et al. Effect of Perioperative pirfenidone treatment in lung cancer patients with idiopathic pulmonary fibrosis. Ann Thorac Surg. 2016; 102: 1905-10.
  28. Raghu G, et al. Effect of nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria. Am J Respir Crit Care Med. 2017; 195: 78-85.
  29. Ogura T, et al. Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2015; 45: 1382-92.
  30. Vancheri C, 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.
  31. Nathan SD, et al. Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax. 2016; 71: 429-35.
  32. Womack CJ, et al. Weight loss, not aerobic exercise, improves pulmonary function in older obese men. J Gerontol A Biol Sci Med Sci. 2000; 55: M453-7.

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