吡非尼酮联合免疫抑制剂治疗结缔组织病相关肺间质性病变的研究进展

Pirfenidone combined with immunosuppressive agents in the treatment of connective tissue disease-related pulmonary interstitial disease.

结缔组织病(connective tissue disease,CTD)常累及全身各个器官,多种CTD如系统性硬化症(systemic sclerosis,SSc)、类风湿关节炎(rheumatoid arthritis,RA)、炎性肌病(idiopathic inflammatory myopathies,IIM)、系统性红斑狼疮(systemic lupus erythematosus,SLE)、干燥综合征(sjogren syndrome,SS)等易累及肺脏,表现为不同病理及影像学亚型,进展速度和预后有显著差异的肺间质病变(interstitial lung disease,ILD),且某些亚型死亡率较高。目前临床上多以糖皮质激素联合免疫抑制剂为一线治疗方案,但其使用时长、维持和减停标准未见明确指南,且部分患者对免疫治疗反应欠佳。另一方面,靶向抗纤维化及抗炎药物吡非尼酮(pirfenidone,PFD)在我国开始尝试应用于多种CTD-ILD患者,但其与免疫治疗的联合方案、桥接时机、使用时长值得探讨。本文将结合近年临床指南和学科进展,对国内外现有文献进行述评,总结PFD联合免疫抑制剂在常见CTD-ILD使用中的研究进展,为临床实践提供参考。

Connective tissue disease(CTD)is a heterogeneous group of systemic disorders that can affect any organ system.Lung involvement is a rather common manifestation of CTD,such as systemic sclerosis,rheumatoid arthritis,inflammatory myopathy,systemic lupus erythematosus,Sjogren’s syndrome,contributing to significant morbidity and mortality.There are different subtypes in pathology and imaging manifestations of interstitial lung disease(ILD)and they may present with subclinical features following a slow or acute progressively course,and turn into clinically significant rapid progression leading to mortality.At present,glucocorticoids combined with immunosuppressive agents are used as the firstline treatment without enough guidelines for their maintenance and decline strategy.Some patients have poor response to it due to their fibrosis progression.On the other hand,the targeted anti-fibrosis and anti-inflammatory drug,pirfenidone(PFD)has been tried to be applied in some kind of CTD-ILD,but their combination with immunotherapy,bridging time and service time are worth discussing.This article will summarize clinical guidelines and academic progress reports in recent years,review the existing literature at home and abroad,the articles of PFD combined with immunosuppressants in CTDILD to provide references for clinical decision.