甲氨蝶呤联合环磷酰胺治疗类风湿关节炎的临床研究

The short-term efficacy and safety of methotrexate and cyc lophosphamide treatment of rheumatoid arthritis

目的评价甲氨蝶呤联合环磷酰胺治疗类风湿关节炎的疗效和安全性。方法符合纳入及排除标准的类风湿关节炎患者随机分为单用甲氨蝶呤(7.5 mg/周)、单用环磷酰胺(400 mg/2周)及甲氨蝶呤联合环磷酰胺治疗组(甲氨蝶呤7.5 mg/周+环磷酰胺400 mg/2周)。疗程24周,在0、6、12、24周进行疗效及安全性评估。以美国风湿病学会疗效评价指标ACR20为主要疗效指标,ACR50、ACR70、欧洲抗风湿病联盟疗效指标、疼痛目视模拟测试表评分、患者对自身健康状况的总体评估、医生总体评价、压痛关节数、压痛关节指数、肿胀关节数、肿胀关节指数、健康评估问卷为次要疗效指标。结果在24周,联合治疗组改善达ACR20标准者为81%,高甲氨蝶呤组56%及环磷酰胺组35%,差异有统计学意义(P<0.05);联合治疗组达ACR50改善的患者比例高于环磷酰胺组(P<0.05),与甲氨蝶呤组之间差异无统计学意义(P>0.05),联合治疗组达到EULAR有效者为77%,高于甲氨蝶呤组48%及环磷酰胺组35%,差异有统计学意义(P<0.05)。联合治疗组在压痛关节数/压痛关节指数、肿胀关节数/肿胀关节指数,疼痛VAS评分、ESR的改善程度高于甲氨蝶呤组(P<0.05),在压痛关节数或指数、肿胀关节数或指数、疼痛VAS评分、PGA、医生总体评价、HAQ、ESR的改善程度高于环磷酰胺组(P<0.05)。3组之间不良反应发生率差异无统计学意义。结论甲氨蝶呤联合环磷酰胺治疗能显著改善类风湿关节炎的症状、体征和实验室炎性指标,疗效优于单用。两者联合治疗安全耐受性好,与单用相比,并不增加不良反应的发生率。

Objective To evaluate the clinical therapeutic and safety of methotre xate（MTX）,cyclophos-phamide（CTX） and MTX plus CTX in patients with active rheum atoid arthritis（RA）. Methods 180 patients were randomly assigned to receive MTX（7.5 mg/w）or CTX（400 mg/2w）or MTX plus CTX（MTX 7.5 mg/2＋CTX400 mg/2w）.The primary end point was the proportion of patients meeting the American College of Rheumatol ogy 20 % improvement criteria（achieving an ACR20 response）at week 24.The second ary end points were responses of the ACR50 and ACR70 improvement criteria,and t he European League Against Rheumatism（EULAR） response criteria.The change from baseline in duration of pain,patient＇s global assessment,physician＇s global as sessment,tender joint count/index,swollen joint count/indes,health assessment qu estionnaire（HAQ）,erythrocyte sedimentation rate（ESR） were also evaluated.The clinical dfficacy and safety were analyzed at baseline,6,12 and 24 weeks respec tively. Results The ACR response rate was significantly higher i n the MTX plus C TX treatment group compared with MTX or CTX group at week 24.The MTX plus CTX gr oup,MTX group and CTX group showed 81 %,56 %and35 %in ACR20,58 %,41 %and 12 %,i n ACR5 0 and 19 %,11 % and 0 in ACR70,respectively.At week 24,the proportion of patien ts achieving the EULAR moderate response in those who received combination treatme nt were significantly higher than those who received either MTX or CTX.The inci dence of adverse events was not significantly higher in MTX plus CTX group than others. Conclusion MTX plus CTX effectively reduces the signs a nd symptoms of RA, and is generally well tolerated by patients without significant increase in the rate of adverse events compared with monotherapy.