中国临床药理学杂志2025，Vol.41Issue(13)：1801-1805,5.DOI:10.13699/j.cnki.1001-6821.2025.13.001
尼达尼布联合环磷酰胺治疗结缔组织病相关间质性肺疾病患者的临床研究
Clinical trial of nintedanib combined with cyclophosphamide in the treatment of patients with interstitial lung disease associated with connective tissue disease
摘要
Abstract
Objective To observe the clinical effect and safety of nintedanib capsule combined with compound cyclophosphamide tablet and prednisone acetate tablet in the treatment of patients with interstitial lung disease(ILD)associated with connective tissue disease(CTD).Methods CTD-ILD patients were randomly divided into control group and treatment group.The control group was given oral prednisone acetate tablets(initial dose:0.5 mg·kg-1·d-1,0.25 mg·kg-1·d-1 after 4 weeks,0.125 mg·kg-1·d-1 after 8 weeks)+compound cyclophosphamide tablets(100 mg·d-1),while treatment group was given oral nintedanib ethanesulfonate soft capsules(150 mg,bid)on basis of control group.All patients were treated for 12 weeks.The clinical curative effect,levels of serum complement C3,C4,Dickkopf-1(DKK-1)and latent transforming growth factor binding proteins 2(LTBP2),score of chest CT and the occurrence of adverse drug reactions were compared between the two groups.Results There were 49 cases in control group and 49 cases in treatment group,without any shedding case.After 12 weeks of treatment,total response rates of treatment group and control group were 89.80％(44 cases/49 cases)and 71.43％(35 cases/49 cases),and the difference was statistically significant(P＜0.05).After 12 weeks of treatment,C3 levels in treatment group and control group were(0.64±0.14)and(0.76±0.12)g·L-1,C4 levels were(72.24±9.87)and(83.54±10.13)mg·L-1,DKK-1 levels were(3.24±1.12)and(4.67±1.24)μg·L-1,LTBP2 levels were(10.65±2.21)and(14.68±1.98)ng·L-1,scores of chest CT were(8.47±2.12)and(10.74±3.65)point,differences were statistically significant(all P＜0.05).The adverse drug reactions in both groups were mainly liver dysfunction,hypertension,edema,gastrointestinal reactions,leukopenia,hemorrhagic cystitis and osteoporosis.There was no significant difference in total incidence of adverse reactions between treatment group and control group(48.98％vs.32.65％,P＞0.05).Conclusion Compared with cyclophosphamide alone,nintedanib combined with cyclophosphamide can effectively inhibit immune response,reduce levels of serum DKK-1 and LTBP2,improve lung function and clinical curative effect in CTD-ILD patients,which has high safety.关键词
尼达尼布胶囊/环磷酰胺片/结缔组织病/间质性肺疾病/安全性评价Key words
nintedanib capsule/cyclophosphamide tablet/connective tissue disease/interstitial lung disease/safety evaluation分类
医药卫生引用本文复制引用
冯娅娆,杨金良,罗寰,郭少英,任占芬,郑学军..尼达尼布联合环磷酰胺治疗结缔组织病相关间质性肺疾病患者的临床研究[J].中国临床药理学杂志,2025,41(13):1801-1805,5.基金项目
河北省医学科学研究课题计划基金资助项目(20240801) （20240801）
