A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis
A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis
复制标题
DOI：
10.1136/ard.2003.020347
复制
发表时间：
2005-01-01
影响因子：
27.4
通讯作者：
Tak, PP
中科院分区：
文献类型：
--
作者：
van Holten, J;Pavelka, K;Tak, PP
目的：评价干扰素β(IFNbeta)联合甲氨蝶呤治疗类风湿关节炎的疗效。方法：209例活动期类风湿关节炎患者，在研究开始前服用甲氨蝶呤至少6个月，连续4周，随机分为安慰剂(0.05毫升或0.5毫升)、干扰素β2.2毫升(0.05毫升)或干扰素β44毫克(0.5毫升)，每周3次，共24周。主要疗效测量是在第24周时放射学评分的变化。次要终点是研究结束时符合ACR 20%改善标准的患者比例。治疗前后取一部分患者的滑膜活检标本。用免疫组织化学方法检测炎性细胞的存在，并用数字图像分析技术对结果进行测量。结果：放射学评分和临床变量分析显示，两组患者的尿胶原蛋白含量均无明显变化，组间差异无统计学意义。滑膜组织光镜下观察，IFNb治疗后炎性细胞浸润积分无明显变化。治疗组之间的尿胶原交联物水平没有变化。结论：在测试的剂量下，IFNb每周三次联合甲氨蝶呤治疗类风湿关节炎患者没有临床或放射学效果。
Objective: To assess the efficacy of interferon beta (IFNbeta) in combination with methotrexate in treatment of patients with rheumatoid arthritis.Methods: 209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFNbeta 2.2 mug ( 0.05 ml), or IFNbeta 44 mug (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study.Results: Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFNb treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups.Conclusions: At the doses tested, treatment with IFNb three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis.