Verschueren P, et al. Ann Rheum Dis. 2015Jan;74(1):27-34.
原文
Methotrexate in combination with other DMARDs is not superior to methotrexate alone forremission induction with moderate-to-high-dose glucocorticoid bridging in earlyrheumatoid arthritis after 16 weeks of treatment: the CareRAtrial.
Objectives: To compare the efficacyand safety of intensive combination strategies with glucocorticoids (GCs) inthe first 16 weeks (W) of earlyrheumatoidarthritis (eRA) treatment, focusing on high-riskpatients, in the Care in early RA trial.
Methods: 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified intohigh risk or low risk according to classical prognostic markers. High-riskpatients (n=290) were randomised to 1/3 treatment strategies:combination therapy for early rheumatoid arthritis (COBRA) Classic(methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg dailyfrom W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRAAvant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6).Treatment modifications to target low-disease activity were mandatory from W8,if desirable and feasible according to the rheumatologist. The primary outcomewas remission (28 joint disease activity score calculated with C-reactiveprotein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints weregood European League Against Rheumatism response, clinically meaningful healthassessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events(AEs) were registered.
Results: Data from 98 Classic, 98Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise,no significant differences were shown in other secondary endpoints. However,therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in69.1% of Avant- Garde patients (p=0.006).
Conclusions: For high-risk eRA, MTX associated with a moderatestep-down dose of GCs was as effective in inducing remission at W16 as DMARDcombination therapies with moderate or high step-down GC doses and it showed amore favourable short-term safety profile.
译文
背景: 在一项代号为CareRA的临床试验中, 针对具有预后不良因素的早期RA患者, 比较传统DMARDs联合强化联合方案与糖皮质激素方案治疗16周时临床疗效与安全性。
方法: 400例未曾接受过DMARDs治疗的早期RA患者按照经典预后标志物分为高风险组和低风险组。高风险组患者(n=290例)被随机分配到以下三种治疗策略组中的一组： 早期RA的联合治疗策略( COBRA, 甲氨蝶呤+柳氮磺胺吡啶+强的松60mg/日并逐步减量至7.5mg/日 )；COBRA SLIM( 甲氨蝶呤+强的松30mg/日减量至5mg/日 )；COBRA Avant-Garde( 甲氨蝶呤+来氟米特+强的松30mg/日减量至5mg/日)。从第8周开始, 如果风湿病医生认为有必要且可行, 他们可以为达到低度疾病活动度而强制性地调整治疗方案。主要观察终点是第16周的临床缓解达标率( DA28- CRP＜2.6 )。统计方法采用ITT分析。次要观察终点为EULAR良好应答达标率、有临床意义的HAQ评分改善以及HAQ评分为零的患者比例。同时记录药物不良事件。
结果:经典COBRA组、Slim组和Avant-Garde组分别提供了98例、98例和94例数据。第16周时, 经典COBRA组早期RA 患者的临床缓解达标率为70.4％, Slim组为73.6%, Avant- Garde组为68.1%( p=0.713 )。次要观察终点的各项指标同样也没有显著的组间差异。然而, 不良事件报告率有显著组间差异, 经典COBRA组为61.2％, Slim组为46.9%, Avant- Garde组为69.1%( p=0.006 )。
讨论:对于具有预后不良因素的高危早期RA患者, 与经典的传统DMARDs联合并加用起始中高剂量糖皮质激素并逐步减量的方案(COBRA方案)治疗16周的临床疗效相比, 甲氨蝶呤联合起始中等剂量糖皮质激素并逐步减量的方案(SLIM方案) 的临床疗效与之相当, 并表现出更有利的短期药物安全性。
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