Sistemik skleroz ilişkili interstisyel akciğer hastalığı ve nintedanib

Year 2022, Volume: 3 Issue: 2, 117 - 121, 28.06.2022

Nurhan Atilla , Gözde Yıldırım Çetin , Burak Okyar , Hüseyin Arpağ

https://doi.org/10.47582/jompac.1090083

Abstract

Sistemik skleroz ile ilişkili interstisyel akciğer hastalığında (SSc-İAH) akciğer fibrozisine yol açan birçok mekanizma öne sürülmesine rağmen, bu konu henüz tam olarak anlaşılamamıştır. Son zamanlarda, idiyopatik pulmoner fibrozdan (İPF) sorumlu aracıların ve patolojik mekanizmaların SSc-İAH’dekilere benzer olduğuna dair kanıtlar artmıştır. Buna göre, İPF tedavisinde kullanılan antifibrotik ajanların SSc-İLD’de de faydalı olabileceğini destekleyen çalışmalar mevcuttur. Şu anda piyasada nintedanib ve pirfenidon olmak üzere iki antifibrotik ajan bulunmaktadır. SSc-İAH’de pirfenidon kullanımına ilişkin çalışmalar tatmin edici olmasa da, nintedanib çalışmaları olumlu sonuçlar vermiştir. SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) çalışması bu konudaki ilk ve en kapsamlı Faz III çalışmasıdır 2019’da SENSCIS çalışmasının sonuçları, nintedanib’in SSc-İAH’de akciğer fonksiyonundaki yıllık düşüşü önemli ölçüde azalttığını göstermiştir. Şiddetli akciğer fonksiyon kaybı olan SSc-İAH hastalarını içermeyen bu çalışmadan sonra, nintedanib dünya çapında SSc-İAH tedavisi için lisans almıştır. Bununla birlikte, şu anda mevcut olan literatür verileri, nintedanibin SSc-İAH üzerindeki uzun vadeli etkileri ve yan etkileri ve ayrıca ileri evre SSc-İAH üzerine etkilerinden yoksundur. Bu çalışmanın amacı, SSc-İAH’de nintedanib kullanımını güncel literatür eşliğinde, bu hastalığın patogenezinden de bahsederek gözden geçirmektir.

Keywords

Sistemik skleroz, nintedanib, akciğer, fibrozis

Systemic sclerosis related interstitial lung disease and nintedanib

Abstract

Although many mechanisms leading to lung fibrosis in systemic sclerosis-associated interstitial lung disease (SSc-ILD) have been suggested, this issue has not been fully understood yet. Recently, there has been increased evidence that the mediators and pathological mechanisms responsible for idiopathic pulmonary fibrosis (IPF) are similar to those in SSc-ILD. Accordingly, studies have been conducted to support that antifibrotic agents used in the treatment of IPF may also be useful in SSc-ILD. There are currently two antifibrotic agents on the market, namely nintedanib and pirfenidon. Although studies on the use of pirfenidone in SSc-ILD are not satisfactory, nintedanib studies have yielded positive results. The SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) study is the first and most comprehensive Phase III study on this subject. In 2019, the results of SENSCIS trial showed that, nintedanib significantly reduced the annual decline in lung function in SSc-ILD. After this trial, which did not include SSc-ILD patients with severe lung function loss, nintedanib licenced for the treatment of SSc-ILD worldwide. However, the currently available literature data lacks information about long-term effects and side effects of nintedanibe on SSc-ILD an also about the advanced SSc-ILD. The aim of this study is to review SSc-ILD patients treated with nintedanib, by also mentioning the pathogenesis of this disease according to the current literature.

Keywords

Sistemik skleroz, nintedanib, akciğer, fibrozis

References

• Denton CP, Khanna DK. Systemic sclerosis. Lancet 2017; 390: 1685-99.
• Kafle S, Magar MT, Patel P, Poudel A, Cancarevic I. Systemic sclerosis associated interstitial lung disease and nintedanib: a rare disease and a promising drug. Cureus 2021; 13: 16404.
• Elhai M, Meune C, Boubaya M, et al. Mapping and predicting mortality from systemic sclerosis. Ann Rheum Dis 2017; 76: 1897-905.
• Roofeh D, Distler O, Allanore Y, Denton CP, Khanna D. Treatment of systemic sclerosis-associated interstitial lung disease: lessons from clinical trials. J Scleroderma Relat Disord 2020; 5: 61-71.
• Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354: 2655-66.
• Strieter RM, Mehrad B. New mechanisms of pulmonary fibrosis. Chest 2009; 136: 1364-70.
• Fernandez IE, Eickelberg O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet 2012; 380: 680-8.
• Mathai SK, Gulati M, Peng X, et al. Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype. Lab Invest 2010; 90: 812-23.
• Huang X, Yang N, Fiore VF, et al. Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic mechanotransduction. Am J Respir Cell Mol Biol 2012; 47: 340-8.
• Roth GJ, Binder R, Colbatzky F, et al. Cancer Res 2008; 68: 4774-83.
• Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 2011; 365: 1079-87.
• Herzog EL, Mathur A, Tager AM, Feghali-Bostwick C, Schneider F, Varga J. Review: interstitial lung disease associated with systemic sclerosis and idiopathic pulmonary fibrosis: how similar and distinct? Arthritis Rheumatol 2014; 66: 1967-78.
• Bagnato G, Harari S. Cellular interactions in the pathogenesis of interstitial lung diseases. Eur Respir Rev 2015; 24: 102-14.
• Duarte AC, Santos MJ, Cordeiro A. Anti-fibrotic nintedanib-a new opportunity for systemic sclerosis patients? Clin Rheumatol 2018; 37: 1123-7.
• Seibold JR, Maher TM, Highland KB, et al. Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial. Ann Rheum Dis 2020; 79: 1478-84.
• Azuma A, Chung L, Behera D, et al. Efficacy and safety of nintedanib in Asian patients with systemic sclerosis-associated interstitial lung disease: Subgroup analysis of the SENSCIS trial. Respir Investig 2021; 59: 252-9.
• Kuwana M, Ogura T, Makino S, et al. Nintedanib in patients with systemic sclerosis-associated interstitial lung disease: a Japanese population analysis of the SENSCIS trial. Modern Rheu J 2021; 31: 141-50.
• Sumi T, Uehara H, Tada M, et al. Spontaneous pneumothorax during nintedanib therapy in patients with systemic sclerosis-associated interstitial lung disease. Respirology Case Reports 2021; 9: 1-4.
• Bordas-Martinez J, Llanos-González AB, Jodar-Masanes R. Experience with nintedanib in severe pulmonary fibrosis associated with systemic sclerosis: a case Series. Open Respiratory Archives J 2021; 3: 1-3.
• Nishino K, Sasatani Y, Ohara G, Kagohashi K, Satoh H. Nintedanib-mediated improvement in CT imaging in pulmonary fibrosis associated with systemic scleroderma. Adv Respir Med 2021; 89: 528-31.