尼达尼布治疗特发性肺纤维化的长期疗效及安全性:单中心参与INPULSIS及INPULSIS ON的系列病例分析  

Long-term clinical efficacy and safety of nintedanib in the treatment of idiopathic pulmonary fibrosis(IPF):case analysis of single center involved in INPULSIS and INPULSIS ON

作　　者：丁旻 李佳旻[1] 洪群英[1] 毛若琳 崔博 马圆 陈智鸿[1] DING Min;LI Jia-min;HONG Qun-ying;MAO Ruo-lin;CUI Bo;MA Yuan;CHEN Zhi-hong(Department of Pulmonary and Critical Care Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Pulmonary and Critical Care Medicine,People's Hospital of Fengcheng,Fengcheng 331100,Jiangxi Province,China)

机构地区：[1]复旦大学附属中山医院呼吸与危重医学科,上海200032 [2]江西丰城人民医院呼吸与危重医学科,丰城331100

出　　处：《复旦学报（医学版）》2022年第3期395-401,共7页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金(81970023);上海市卫健委课题(201840288);上海市重中之重临床建设项目(2017ZZ02013)。

摘　　要：目的探讨尼达尼布治疗特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的长期临床疗效及安全性。方法本中心于2012年7月起参加全球尼达尼布治疗IPF的为期52周的随机双盲Ⅲ期临床试验(INPULSIS,INPULSIS ON),共入组10例IPF患者。1年研究结束后,继续追踪随访至今,共约9年。经揭盲分析后发现,试验组(尼达尼布组)6例,对照组(安慰剂组)4例。记录治疗前后两组患者用力肺活量(FVC绝对值及FVC%pre)、一氧化碳弥散量(DLCO%pre)、SGRQ评分的变化及急性发作次数,持续记录患者的生存状况,并观察不良反应发生情况。结果治疗前两组FVC和DLCO无显著差异,治疗后试验组FVC下降趋势相对较缓,FVC%pre年下降率为2%,对照组为4.9%。DLCO的年下降率及SGRQ评分变化两组无明显差异。随访期间8例患者病死,其中试验组4例(4/6),对照组4例(4/4)。Kaplan-Meier生存曲线发现试验组有生存优势,但由于病例数少,未达到统计学差异。试验组不良反应发生率为50%(3/6),多为腹泻、腹部不适。程度多为轻至中度。2例生存至今的受试者,1例服用尼达尼布至今,1例服用尼达尼布1.5年后因腹泻退出研究。这2例肺功能追踪发现,长期服用尼达尼布者FVC%pre更稳定,急性加重次数较少。而中途停药者8年时复查FVC%pre已下降24.8%,急性加重3次。结论尼达尼布可能延缓IPF患者FVC的下降趋势及延长生存时间,减少急性加重,长期服用具有较好的耐受性。Objective To investigate the long-term clinical efficacy and safety of nintedanib in the treatment of idiopathic pulmonary fibrosis(IPF).Methods Since July 2012,our center has participated in the global 52-week randomized,double-blind,phaseⅢclinical trial(INPULSIS,INPULSIS ON)of nintedanib in the treatment of idiopathic pulmonary fibrosis(IPF),and 10 patients with IPF were enrolled.At the end of the 1-year study,follow-up was continued up to now for about 9 years.After unblinding,6 patients were in the experimental group(nintedanib group)and 4 patients in the control group(placebo group).Changes of forced vital capacity(FVC absolute value and FVC%pre),diffusing capacity of the lung for carbon monoxide(DLCO%pre),SGRQ score and the frequency of acute exacerbation in the two groups before and after treatment were recorded.The survival statuses of patients were continuously recorded,and the occurrence of adverse reaction was observed.Results There was no significant difference in FVC and DLCO between the two groups before treatment.After treatment,FVC decreased slowly in the experimental group and the FVC%pre annual decrease rate was 2%and 4.9%in the control group.The annual decrease rate of DLCO and the change of SGRQ score had no significant difference between the two groups.During the follow-up period,8 patients died,including 4 cases in the experimental group(4/6)and 4 cases in the control group(4/4).Kaplan-Meier survival curve found that the experimental group had a survival advantage,but the difference did not reach statistical significance due to the small sample capacity.The incidence of adverse reactions in the experimental group was 50%(3/6),mostly were diarrhea and abdominal discomfort,and the degree was mostly mild to moderate.Among the two cases who were still survived,one has been taking nintedanib until now,and the other dropped out of the study due to diarrhea 1.5 years after taking nintedanib.The pulmonary function of these two patients showed that the FVC%pre was more stable and the frequency of a

关 键 词：特发性肺纤维化(IPF) 尼达尼布 长期疗效 不良反应 

分 类 号：R563[医药卫生—呼吸系统]