Research Progress of Pirfenidone for connective tissue disease-associated interstitial lung diseases

doi:10.12092/j.issn.1009-2501.2020.05.016

Abstract

Abstract: Pirfenidone is an anti-fibrotic drug that has been shown to reduce the decline of lung function in patients with idiopathic pulmonary fibrosis (IPF) in multiple clinical trials, and has become first-line drugs for the treatment of IPF. Similar to the pathogenesis of IPF , clinical incidence of connective tissue disease-associated interstitial lung diseases (CTD-ILD) is high, and the clinical performance is not obvious. ILD may be the only or the original manifestation. Thus the clinical heterogeneity and the misdiagnosis rate are relatively high. Also, CTD-ILD is one of the important reasons that resulted in the death of patients. Currently, the clinical diagnosis and treatment of CTD-ILD still lack effective guide or unified agreement. Studies have shown that anti fibrosis drug pirfenidone shows some potential in the treatment of CTD-ILD. Here we summarize the research advances of pirfenidone in the treatment of CTD-ILD.

Key words: pirfenidone, conective tissue disease, interstitial lung disease

CLC Number:

R563
R974

WANG Xiao, YUE Hongmei, WANG Ruoli, SUN Jinying, LI Le, LIU Ruichao. Research Progress of Pirfenidone for connective tissue disease-associated interstitial lung diseases[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(5): 584-590.

References

[1]Atzeni F, Gerardi M, Barilaro G, et al. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review [J]. Expert Rev Clin Immunol, 2018, 14(1): 69-82.
[2]Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibosis: An update of the 2011 clinical practice guideline [J]. Am J Respir Crit Care Med, 2015, 192(2): 3 -19.
[3]Miura Y, Saito T, Fujita K, et al. Clinical experience with pirfenidone in five patients with scleroderma-related interstitial lung disease [J]. Sarcoidosis Vasc Diffuse Lung Dis, 2014,31(3) :235- 238.
[4]Khanna D, Albera C, Fischer A, et al. An open-label, phase II study of the safety and tolerability of pirfenidone in patients with scleroderma-associated interstitial lung disease: the LOTUSS Trial [J]. J Rheumatol, 2016, 43(9): 1672-1679.
[5]Solomon J, Danoff S, Goldberg H,et al. The design and rationale of the trail1 trial: A randomized double-blind phase 2 clinical trial of pirfenidone in rheumatoid arthritis-associated interstitial lung disease [J]. Adv Ther, 2019, 36(11): 3279-3287 .
[6]Gan Y, Herzog E, Gomer R. Pirfenidone treatment of idiopathic pulmonary fibrosis [J]. Ther Clin Risk Manag, 2011, 7: 39-47.
[7]Togami K, Kanehira Y, Tada H. Pharmacokinetic evaluation of tissue distribution of pirfenidone and its metabolites for idiopathic pulmonary fibrosis therapy [J]. Biopharm Drug Dispos, 2015, 36(4): 205-215.
[8]Pan L, Gelzleichter T, Chen Y, et al. Effect of pirfenidone on gastric emptying in a rat model [J]. Pulm Pharmacol Ther, 2018, 51: 41-47.
[9]Khoo JK, Montgomery AB, Otto KL, et al. A randomized, double-blinded, placebo- controlled, dose-escalation phase 1 study of aerosolized Pirfenidone delivered via the PARI investigational eFlow nebulizer in volunteers and patients with idiopathic pulmonary fibrosis [J]. J Aerosol Med Pulm Drug Deliv, 2020, 33(1): 15-20.
[10]Surber M, Poulin D, McInally K, et al. Inhaled Pirfenidone improves animal efficacy through superior pulmonary and vascular pharmacokinetics [J]. Am J Resp Crit Care, 2014, 189: 6599.
[11]Kaminskas L, Landersdorfer C, Bischof R,et al. Aerosol pirfenidone pharmacokinetics after Inhaled delivery in sheep: a viable approach to treating idiopathic pulmonary fibrosis [J]. Pharm Res, 2019, 37(1): 3.
[12]Skold C, Bendstrup E, Myllarniemi M, et al. Treatment of idiopathic pulmonary fibrosis: a position paper from a Nordic expert group [J]. J Intern Med, 2017, 281(2) : 149-166.
[13]Ruwanpura S, Thomas B. Pirfenidone: Molecular mechanisms and potential clinical applications in lung disease [J]. Am J Respir Cell Mol Biol, 2020, 62(4): 413-422.
[14]Qin W, Liu B, Yi M, et al. Antifibrotic agent pirfenidone protects against development of radiation-induced pulmonary fibrosis in a murine model [J]. Radiat Res, 2018, 190(4): 396-403.
[15]Vicens-Zygmunt V, Estany S, Colom A, et al. Fibroblast viability and phenotypic changes within glycated stiffened three-dimensional collagen matrices [J]. Respir Res, 2015, 16: 82.
[16]Ma Z, Zhao C, Chen Q, et al. Antifibrotic effects of a novel pirfenidone derivative in vitro and in vivo [J]. Pulm Pharmacol Ther, 2018, 53: 100-106.
[17]Molina-Molina M, Machahua-Huamani C, Vicens-Zygmunt V, et al. Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells [J]. BMC Pulm Med, 2018, 18(1): 63.
[18]Pourgholamhossein F, Rasooli R, Pournamdari M, et al. Pirfenidone protects against paraquat-induced lung injury and fibrosis in mice by modulation of inflammation, oxidative stress, and gene expression [J]. Food Chem Toxicol, 2018, 112: 39-46.
[19]Nakayama S, Mukae H, Sakamoto N, et al. Pirfenidone inhibits the expression of hsp47 in tgf-beta1- stimulated human lung fibroblasts [J]. Life Sci, 2008, 82(3/4): 210-217.
[20]Kakugawa T, Mukae H, Hayashi T, et al. Pirfenidone attenuates expression of hsp47 in murine bleomycin-induced pulmonary fibrosis [J]. Eur Respir J, 2004, 24(1): 57-65.
[21]Yu W, Guo F. Effects and mechanisms of pirfenidone, prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models [J]. Pharm Biol, 2017, 55(1): 450-455.
[22]Kurita Y, Araya J, Minagawa S, et al. Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy [J]. Respir Res, 2017, 18(1): 114.
[23]Giannandrea M, Parks W. Diverse functions of matrix metalloproteinases during fibrosis [J]. Dis Model Mech, 2014, 7(2): 193-203.
[24]Tian X, Yao W, Guo Z, et al. Low dose pirfenidone suppresses transforming growth factor beta-1 and tissue inhibitor of metalloproteinase-1, and protects rats from lung fibrosis induced by bleomycina [J]. Chin Med Sci J, 2006, 21(3): 145-151.
[25]Rasooli R, Rajaian H, Pardakhty A, et al. Preference of aerosolized pirfenidone to oral intake: An experimental model of pulmonary fibrosis by paraquat [J]. J Aerosol Med Pulm Drug Deliv, 2018, 31(1): 25-32.
[26]Shi Q, Liu X, Bai Y,et al. In vitro effects of pirfenidone on cardiac fibroblasts: Proliferation, myofibroblast differentiation, migration and cytokine secretion [J]. PLoS One, 2011, 6(11): e28134.
[27]Tamargo J, Lopez-Sendon J. Novel therapeutic targets for the treatment of heart failure [J]. Nat Rev Drug Discov, 2011, 10(7): 536-555.
[28]Ruwanpura SM,Rosli S.Lung Diseases [J]. Exp Suppl, 2018, 108: 61-84.
[29]Li Y, Li H, Liu S, et al. Pirfenidone ameliorates lipopolysaccharide-induced pulmonary inflammation and fibrosis by blocking nlrp3 inflammasome activation [J].Mol Immunol, 2018, 99: 134-144.
[30]Distler O, Assassi S, Cottin V, et al. Predictors of progression in systemic sclerosis patients with interstitial lung disease [J]. Eur Respir J, 2020, doi: 10.1183/13993003.02026.2019.
[31]Hsu E, Shi H, Jordan R, et al. Lung tissues in patients with systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension [J]. Arthritis Rheum, 2011, 63(3): 783-794.
[32]Peljto A, Steele M, Fingerlin T, et al. The pulmonary fibrosis associated MUC5B promoter polymorphism does not influence the development of interstitial pneumonia in systemic sclerosis [J]. Chest, 2012, 142(6): 1584-1588.
[33]Ytterberg AJ, Joshua V, Reynisdottir G, et al. Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis: identification and validation [J]. Ann Rheum Dis, 2015, 74(9): 1772-1777.
[34]中国医师协会风湿免疫科医师分会风湿病相关肺血管/间质病学组, 国家风湿病数据中心. 2018中国结缔组织病相关间质性肺病诊断和治疗专家共识 [J]. 中华内科杂志, 2018, 57(8): 558-565.
[35]Ahuja J, Arora D, Kanne JP, et al. Imaging of pulmonary manifestations of connective tissue diseases [J]. Radiol Clin North Am, 2016, 54(6): 1015-1031.
[36]Gao Y. Treatment of the connective tissue disease-related interstitial lung diseases: A narrative review [J]. Mayo Clin Proc, 2020, 95(3): 554-573.
[37]Khanna D, Tashkin DP, Denton CP, et al. Etiology, risk factors, and biomarkers in systemic sclerosis with Interstitial lung disease [J]. Am J Respir Crit Care Med, 2020, 201(6): 650-660.
[38]Yunt Z, Chung J, Hobbs S, et al. High resolution computed tomography pattern of usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease: Relationship to survival [J]. Respir Med, 2017, 126: 100-104.
[39]Atzeni F, Gerardi M, Barilaro G, et al. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review [J]. Expert Rev Clin Immunol, 2018, 14(1): 69-82.
[40]Paulin F, Doyle T, Fletcher E, et al. Rheumatoid arthritis-associated interstitial lung disease and idiopathic pulmonary fibrosis: shared mechanistic and phenotypic traits suggest overlapping disease mechanisms [J]. Rev Investig Clin, 2015, 67(5): 280-286.
[41]Wu C, Lin H. Inhibitory effects of pirfenidone on fibroblast to myofibroblast transition in rheumatoid arthritis-associated interstitial lung disease via the downregulation of activating transcription factor 3 (ATF3) [J]. Int Immunopharmacol, 2019, 74: 105700.
[42]Li T, Guo L, Chen Z, et al. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis [J]. Sci Rep, 2016, 6: 33226.
[43]邱明亮, 姜楠, 吴婵媛, 等. 吡非尼酮治疗结缔组织病相关肺间质病变三例及文献复习 [J]. 中华临床免疫和变态反应杂志, 2017, 11(1): 6-13.
[44]王红梅, 杨佳丹, 蒙龙, 等. 吡非尼酮治疗特发性肺纤维化疗效与安全性的系统评价 [J]. 中国药房, 2016, 27(3): 345-348.
[45]Lancaster L, Albera C, Bradford W, et al. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials [J]. BMJ Open Respir Res, 2016, 3(1): e000105.
[46]King T, Bradford W, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathicpulmonary fibrosis [J]. N Engl J Med, 2014, 370(22): 2083-2092.