尼达尼布抗纤维化治疗特发性肺纤维化的耐受性和疗效预测因素分析  

Analysis of tolerance and efficacy factors of Nintedanib anti-fibrotic in the treatment of idiopathic pulmonary fibrosis

作　　者：王亚岚 倪婧 余世庆 陶银花 张荣 Wang Yalan;Ni Jing;Yu Shiqing;Tao Yinhua;Zhang Rong(Department of Respiratory Medicine,The Fourth Affiliated Hospital of Nanjing Medical University,Nanjing 210031,China)

机构地区：[1]南京医科大学第四附属医院呼吸内科,南京210031

出　　处：《中华肺部疾病杂志（电子版）》2024年第5期750-755,共6页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：江苏省卫生厅预防医学基金科研课题(Y2020043)。

摘　　要：目的分析尼达尼布(nedanib,NT)治疗特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的耐受性和疗效预测因素。方法选择2020年3月至2023年12月我院收治的67例IPF患者,接受初始计量为300 mg的NT治疗,治疗前(入组当天)以及治疗6个月(M)、12 M行胸部计算机断层扫描及肺功能检测。记录IPF患者的不良事件发生情况。结果12M期间45例(67.16%)IPF患者NT剂量减少,6 M内34例剂量减少,剂量减少的原因为发生不良事件。20例(29.85%)12 M期间停用NT,6 M内10例的停药发生,不良事件是常见的停药原因。≥75岁的IPF患者6 M期间剂量减少22例(62.86%)较<75岁患者12例(37.50%)高,停用NT的原因多数为不良事件的发生(P<0.05)。LASSO及多因素Logistic回归分析,女性、用力肺活量占预计值的百分比(FVC%pre)<76.70%、表面活性蛋白-D(surfactant protein D,SP-D)≥263.50 ng/ml为IPF患者12 M内NT停药的危险因素,风险评分[1×(女性)+1×(FVC%pre<76.70%)+1×(SP-D≥263.50 ng/ml)]预测IPF患者12 M内NT停药的受试者工作特征曲线下面积为0.760(95%CI:0.688~0.822)。持续NT治疗IPF患者的FVC下降程度小于停用NT治疗组[0.03(-0.16,0.27)L vs.-0.14(-0.50,0.07)L,Z=-2.405,P=0.016],Spearman秩相关分析显示,FVC变化与体质量指数(body mass index,BMI)(Rho=0.410,P<0.001)、FVC%pre(Rho=0.427,P<0.001)呈负相关性。结论IPF患者12 M期间NT剂量减少、停用NT的主要原因为不良事件,根据性别、FVC%pre、SP-D设计的风险评分可预测12 M内NT停药的发生。12 M期间NT持续治疗的患者较停药的患者FVC下降程度小,FVC变化与BMI、FVC%pre有关。Objective To analyze the tolerability and efficacy predictors of nintedanib(NT)in the treatment of idiopathic pulmonary fibrosis(IPF).Methods Prospective inclusion of 67 patients with IPF between March 2020 and December 2023,all patients were the initial measurement of 300 mg of NT treatment,and(in group)on the day before treatment,chest CT scan and lung function test were performed before treatment(the day of enrollment)and at 6 months(M)and 12 M treatment.The occurrence of adverse events in IPF patients was recorded.Results A total of 45(67.16%)IPF patients experienced a reduction in NT dose during 12 M,of which 34 patients experienced a reduction within 6 M,and the reason for this reduction in all patients NT dose are adverse events happened,a total of 20(29.85%)IPF patients stopped NT within 12 M,and 10 of them stopped NT within 6 M,Adverse events were the most common reason for discontinuation in our study.IPF patients≥75 years old had a higher incidence of dose reduction during 6 M,and most patients discontinued NT because of the occurrence of adverse events(P<0.05).According to the LASSO and multiariable Logistic regression analysis,the female,forced vital capacit to the predicted value(FVC%pre)<76.70%,surfactant protein D(SP-D)≥263.50 ng/ml for IPF patients 12 M NT independent risk factors for the development of drug discontinuation,The area under the receiver operating characteristic curve of risk score[1×(female)+1×(FVC%pre<76.70%)+1×(SP-D≥263.50 ng/ml)]for predicting the discontinuation of NT therapy within 12 M in IPF patients was 0.760(95%CI:0.688-0.822).FVC decline in IPF patients with continued NT therapy was significantly less than that in patients with discontinued NT therapy[0.03(-0.16,0.27)L vs.-0.14(-0.50,0.07)L,Z=-2.405,P=0.016].FVC change was negatively correlated with body mass index(BMI)(Rho=0.410,P<0.001)and FVC%pre(Rho=0.427,P<0.001).Conclusion The results of this study showed that the main causes of NT dose reduction and NT discontinuation in IPF patients during 12 M were adver

关 键 词：特发性肺纤维化 尼达尼布 耐受性 疗效预测 

分 类 号：R563[医药卫生—呼吸系统]