吗替麦考酚酯与环磷酰胺治疗结缔组织病相关肺间质病变的随机对照研究  

Randomized control multi-center clinical study of mycophenolate mofetil and cyclophosphamide in the treatment of connective tissue disease related interstitial lung disease

作　　者：张光峰[1] 徐婷[1] 张红卫[2] 叶珊慧[3] 王庆文[4] 张丽君[5] 雷云霞[1] 罗日强[1] 张晓[1] 

机构地区：[1]广东省人民医院广东省医学科学院风湿科,广州510080 [2]广东省佛山市第一人民医院风湿科 [3]广州医科大学附属第一医院风湿科 [4]北京大学深圳医院风湿科 [5]香港大学深圳医院风湿科

出　　处：《中华医学杂志》2015年第45期3641-3645,共5页National Medical Journal of China

摘　　要：目的观察吗替麦考酚酯治疗结缔组织病相关肺间质病变（CTD—ILD）的疗效及安全性。方法选择2011年7月至2014年7月广东省人民医院广东省医学科学院等5家医院收治的结缔组织病患者，经高分辨CT（HRCT）证实有肺间质病变，在应用激素的基础上分别静脉滴注环磷酰胺（A组）或口服吗替麦考酚酯（B组）治疗1年。用药期间分别于第0、3、6及12个月监测肺功能，1年后评价HRCT变化情况。记录所有不良反应。1年后进行疗效和安全性的评价。结果入组患者共60例，每组30例，其中A组5例自愿退出，2例死亡；B组5例自愿退出，3例死亡。共45例如期完成了试验。两组无论组间、组内在用力肺活量（FVC）、一氧化碳弥散功能（DLCo）、一秒用力呼气容积（FEV1）及HRCT和不良反应上差异均无统计学意义（均P〉0．05）。对FVC％≤75％、FEV1％≤75％的患者A组均在第6个月与治疗前差异均有统计学意义（均P〈0．05），而B组则在第12个月时与治疗前差异均有统计学意义（均P〈0．05），两组间差异无统计学意义。对DLCo％≤65％的患者，A组在第3个月开始与治疗前相比差异均有统计学意义（P分别为〈0．01，〈0．01及〈0．05），而B组内差异无统计学意义（P〉0．05），两组间差异也无统计学意义。两组治疗在影响患者生存率上差异无统计学意义（P〉0．05）。结论吗替麦考酚酯在缓解或稳定CTD—ILD患者的肺功能及影像学改变上其总体疗效及生存率与环磷酰胺相当，而且耐受性良好。Objective To investigate the efficacy and safety of mycophenolate mofetil （MMF） in the treatment of connective tissue disease-related interstitial lung disease （CTD-ILD）. Methods A total of 60 patients with CTD-ILD, confirmed by high resolution computer tomography （HRCT）, were enrolled from five clinical centers from July 2010 to July 2014. In addition to the basic glucocorticoid treatment, patients received intravenous cyclophosphamide （Group A ） or oral MMF （Group B ） for one year. Pulmonary function was assessed at the 3,6, 12 months. All adverse events were recorded and efficacy and safety were evaluated at the end of this trial. Results Total 60 patients were enrolled, each group had 30 patients. 5 patients withdrew voluntarily from each group, 2 and 3 patients died in group A and B, respectively. Total 45 patients completed this trial. Neither lung function, HRCT nor adverse events had differences between the two groups or within group （ P 〉 0.05 ） . When the analysis was done among patients with forced vital capacity （ FVC ） ≤75% and forced expiratory volume in one second （ FEV1 ） % ≤ 75% , there were significantly statistical differences in FVC and FEV1 at 6th month compared with prior treatment in group A （both P 〈0. 05）. And there were significant increase in FVC and FEV1 at 12 months in group B （both P 〈 0. 05 ）. But there was no statistical difference between the two groups. For the patients with diffusioncapacity for carbon monoxide （DLco） ≤65%, there were significant increase in group A at 3, 6 and 12 months （P 〈0. 01, P 〈0.05, P 〈0.05, respectively）, but no significant increase was found in patients on MMF. And there was no difference between the two groups. No statistical difference existed in survival rate between these two groups （ P 〉 0. 05 ）. Conclusions MMF has comparative effect as cyclophosphamide in the remission or stability of lung function and HRCT manifestations of CTD-ILD patients. MMF is generally well-tolerated,

关 键 词：结缔组织病 肺部病变 间质 吗替麦考酚酯 环磷酰胺 治疗 

分 类 号：R593.2[医药卫生—内科学]