Hetland M L, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen L S, Tarp U, Svendsen A, Pedersen J K, Skjødt H, Lauridsen U B, Ellingsen T, Hansen G V O, Lindegaard H, Vestergaard A, Jurik A G, Østergaard M, Hørslev-Petersen K
Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark.
Ann Rheum Dis. 2008 Jun;67(6):815-22. doi: 10.1136/ard.2007.076307. Epub 2007 Sep 18.
To investigate whether clinical and radiographic disease control can be achieved and maintained in patients with early, active rheumatoid arthritis (RA) during the second year of aggressive treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and intra-articular corticosteroid. This paper presents the results of the second year of the randomised, controlled double-blind CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) study.
160 patients with early RA (duration <6 months) were randomised to receive intra-articular betamethasone in any swollen joint in combination with step-up treatment with either methotrexate and placebo-ciclosporine (monotherapy) or methotrexate plus ciclosporine (combination therapy) during the first 76 weeks. At week 68 hydroxychlorochine 200 mg daily was added. From week 76-104 ciclosporine/placebo-ciclosporine was tapered to zero.
American College of Rheumatology 20% improvement (ACR20), ACR50 and ACR70 levels were achieved in 88%, 79% and 59% of patients in the combination vs 72%, 62% and 54% in the monotherapy group (p = 0.03, 0.02 and 0.6 between groups). The patients globally declined from 50 to 12 vs 52 to 9, with 51% and 50% in Disease Activity Score (DAS) remission, respectively. Mean (SD) progressions in total Sharp-van der Heijde scores were 1.42 (3.52) and 2.03 (5.86) in combination and monotherapy groups, respectively (not significant). Serum creatinine levels increased by 7% in the combination group (4% in monotherapy), but hypertension was not more prevalent.
Continuous methotrexate and intra-articular corticosteroid treatment resulted in excellent clinical response and disease control at 2 years, and the radiographic erosive progression was minimal. Addition of ciclosporine during the first 76 weeks resulted in significantly better ACR20 and ACR50 responses, but did not have any additional effect on remission rate and radiographic outcome.
研究在使用传统改善病情抗风湿药（DMARDs）和关节内注射皮质类固醇进行积极治疗的第二年，早期活动类风湿关节炎（RA）患者是否能实现并维持临床和影像学疾病控制。本文介绍了随机对照双盲CIMESTRA（类风湿关节炎中的环孢素、甲氨蝶呤、类固醇）研究的第二年结果。
160例早期RA（病程<6个月）患者被随机分组，在最初76周内，任何肿胀关节接受关节内注射倍他米松，同时联合甲氨蝶呤和安慰剂 - 环孢素（单药治疗）或甲氨蝶呤加环孢素（联合治疗）的逐步治疗。在第68周时，每天添加200毫克羟氯喹。从第76 - 104周，环孢素/安慰剂 - 环孢素逐渐减量至零。
联合治疗组88%、79%和59%的患者达到美国风湿病学会20%改善（ACR20）、ACR50和ACR70水平，而单药治疗组分别为72%、62%和54%（组间p = 0.03、0.02和0.6）。患者总体病情从50降至12，而单药治疗组从52降至9，疾病活动评分（DAS）缓解率分别为51%和50%。联合治疗组和单药治疗组总Sharp - van der Heijde评分的平均（标准差）进展分别为1.42（3.52）和2.03（5.86）（无显著差异）。联合治疗组血清肌酐水平升高7%（单药治疗组为4%），但高血压患病率无更高。
持续使用甲氨蝶呤和关节内注射皮质类固醇治疗在2年时产生了良好的临床反应和疾病控制，影像学侵蚀进展最小。在最初76周添加环孢素导致ACR20和ACR50反应显著更好，但对缓解率和影像学结果没有任何额外影响。
