甲氨蝶呤联合环磷酰胺治疗类风湿关节炎随机单盲对照临床研究  

The short-term efficacy and safety of methotrexate and cyclophosphamide treatment of rheumatoid arthritis： a randomized, single-blinded and controlled study

作　　者：李小峰[1] 张莉芸[1] 牛红青 茹晋丽[1] 王彩虹[1] 高晋芳[1] 

机构地区：[1]山西医科大学第二医院风湿免疫科,太原030001 [2]中华风湿病学杂志社

出　　处：《中华风湿病学杂志》2010年第2期110-114,共5页Chinese Journal of Rheumatology

基　　金：山西省卫生厅科技攻关项目（200614）

摘　　要：目的评价甲氨蝶呤（MTX）联合环磷酰胺（CTX）及单独应用MTX、单独应用CTX治疗类风湿关节炎（RA）的疗效和安全性。方法本研究为随机、单盲、对照的临床试验。符合纳入及排除标准的RA患者随机分为单用MTX（10～15mg／周）、单用CTX（400rag／2～3周）及Mrrx联合CTX治疗组（MTX10-15m静倜＋CTX 400mg/2～3周）。疗程24周，在基线、6、12、24周进行疗效及安全性评估。以美目风湿病学会（ACR）疗效评价指标ACR20为主要疗效指标，ACR50、ACR70、欧洲抗风湿联盟（EULAR）疗效指标、疼痛目视模拟测试表（VAS）评分、患者对自身健康状况的总体评估（PGA）、医生总体评价、压痛关节数（TJC）、压痛关节指数（TJI）、肿胀关节数（SJC）、肿胀关节指数（SJI）、健康评估问卷（HAQ）为次要疗效指标。结果在第24周，MTX＋CTX组达ACR20改善的患者比例（81％）高于MTX组（56％）及CTX组（35％），差异有统计学意义（P〈0．05）。24周时MTX＋CTX组达ACR50改善的患者比例高于CTX组（P〈0．05），与MTX组之间差异无统计学意义（P〉0．05）。在第24周，MTX＋CTX组达到EULAR有效的患者比例（77％）高于MTX组（48％）及CTX组（35％），差异有统计学意义（P〈0．05）。24周时MTX＋CTX组在TJC／TJI、SJC／SJI疼痛VAS评分、ESR的改善程度高于MTX组（P〈0．05），在压痛关节数／指数、肿胀关节数／指数、疼痛VAS评分、PGA、医生总体评价、HAQ、ESR的改善程度高于CTX组（P〈0．05）。3组之间不良反应发生率差异无统计学意义。结论MTX联合CTX治疗能显著改善RA的症状、体征和实验室炎性指标，疗效优于单用MTX及单用CTX。两者联合治疗安全耐受性好，与单用MTX及单用CTX相比，并不增加不良反应的发生率。Objective To evaluate the clinical efficacy and safety of methotrexate （MTX）, cyclophos- phamide （CTX） and MTX plus CTX in patients with active rheumatoid arthritis （RA）. Methods In a randomized, single-blinded, controlled study, 90 patients were randomly assigned to receive MTX （10-15 mg/w） or CTX （400 mg/2-3 w） or MTX plus CTX （MTX 10-15 mg/w＋CTX 400 mg/2-3 w）. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% imprnvemeut criteria （achieving an ACR20 response） at week 24. The secondary end points were responses of the ACRS0 and ACR70 improvement criteria, and the European League Against Rheumatism （EULAR） response criteria. Tile change from baseline in duration of pain, patient＇s global assessment, physician＇s global assessment, tender jnint count/ index, swollen joint count/index, health assessment questionnaire（HAQ）, erythrocyte sedimentation rate （ESR） were also evaluated. The clinical efficacy and safety were analyzed at baseline, 6, 12 and 24 weeks respec- tively. Results The ACR response rate was significantly higher in the MTX plus CTX treatment group compared with MTX or CTX group at week 24. The MTX plus CTX group, MTX group and CTX group showed 81%, 56% and 35% in ACR20, 58%, 41% and 12% in ACR50 and 19%, 11% and 0 in ACR70, respectively. At week 24, the proportion of patients achieving the EULAR moderate response in those who received combination treatment were significantly higher than those who received either MTX or CTX. The incidence of adverse events （AEs） was not significantly higher in MTX plus CTX group than MTX or CTX group.Conclusion MTX plus CTX effectively reduces the signs and symptoms of RA and is generally well tolerated by patients without significant increase in the rate of adverse events compared with monotherapy.

关 键 词：关节炎 类风湿 甲氦蝶呤 环磷酰胺 疗效 安全性 

分 类 号：R593.22[医药卫生—内科学] R756.2[医药卫生—临床医学]