COMET亚分析_极早期RA vs早期RA

原文

译文

AB0439

ACHIEVEMENT OF 0 OR 1 SWOLLEN JOINTS AND REMISSION IN VERY EARLY (≤4 MONTHS) OR EARLY (4-24 MONTHS) RHEUMATOID ARTHRITIS WITH ETANERCEPT + METHOTREXATE VS. METHOTREXATE ALONE

P. Emery ^1,*, B. Freundlich ², D. Robertson ³, T. Ferdousi ³, E. Bananis ³, R. Pedersen ³, A. S. Koenig ³

¹Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, United Kingdom, ²University of Pennsylvania, Phildelphia, PA, ³Pfizer Inc., Collegeville, PA, United States

Background: New ACR/EULAR remission criteria for rheumatoid arthritis (RA) include achievement of 0 or 1 swollen joints (SJ) and a simplified disease activity index (SDAI) score of ≤3.3. The COMET trial (Combination of MTX and ETN in Active Early Rheumatoid Arthritis) demonstrated that treatment of early RA with methotrexate (MTX) alone or in combination with etanercept (ETN) leads to reduced disease activity.¹ Post hoc sub-analyses suggested that RA patients (pts) benefit from treatment at very early stage RA (VERA, ≤4 months) compared to early stage RA (ERA, 4 months–24 months).²

Objectives: This post hoc analysis of data from the COMET trial examines the incidence of achievement ≤1 SJ, SDAI (≤3.3) and DAS28 (≤2.6) remission in response to treatment in pts with ERA and VERA at week (wk) 52 of treatment.

Methods: Overall study methods have been previously described.^2,3 For this analysis, observed data from the COMET study (NCT00195494) was assessed at wk 52 by treatment group for baseline duration effect of ERA or VERA. Pts who discontinued treatment due to lack of efficacy at ≤ 52 wks were included as non-responders.

Results: At study entry pts had an average 17 SJs. At 52 wks of treatment, significantly more ERA pts achieved ≤1 SJ when treated with ETN + MTX vs. MTX alone (70% vs. 46% respectively, P<0.0001, Table). Although not significant, more VERA pts on combination therapy attained ≤1 SJ when treated (75% vs. 59%, respectively, P=0.0853). More pts treated with ETN + MTX achieved SDAI remission than those treated with MTX alone. However, significance was only shown in ERA pts due to the small number of VERA pts. Of the VERA pts who had ≤1 SJ, the majority also achieved DAS28 remission (ETN+MTX, 85%, MTX alone, 55%) as compared to pts >1 SJ (25% and 5%, respectively). This trend was also seen in the ERA pts treated with ETN+MTX or MTX alone, those with ≤1 SJ achieved DAS28 remission (64% and 60%, respectively) as compared to pts >1 SJ (11% and 8%, respectively).

*Regardless of SJ number; ^†P (for treatment effect) <0.05; ^‡ DAS28 remission defined as score of <2.6; ^§Data not available for calculating SDAI for all pts;**SDAI remission defined as score of ≤3.3.

Conclusions: Per EULAR recommendations, treatment should result in the lowest disease state achievable³. Here, pts with VERA and ERA who were treated with ETN + MTX had higher probability of achieving remission (DAS28 and SDAI) and ≤1 SJ at wk 52 compared to pts treated with MTX alone. After one year of therapy, almost ¾ of pts who were treated with combination therapy had ≤1 SJC and most but not all had remission, supporting early intervention.

References: 1. Emery P, et al. Lancet 2008; 372(9636):375-382

2. Emery P, et al. Ann Rheum Dis 2010;69(Suppl3):57

3. Smolen J, et al. Ann Rheum Dis 2010;69:964-975

Table. Achievements of ≤1 swollen joints or remission at Week 52 by pt group and treatment

By pt group

Pt Group

Treatment

≤1 SJ*, %

DAS28 Remission*^‡ %

n^§

SDAI Remission*^,**
%

VERA

ETN +MTX (n=63)

MTX alone (n=49)

74.6

59.2

69.8^†

34.7^†

24.1

13.6

ERA

ETN +MTX (n=157)

MTX alone (n=148)

70.1^†

45.9^†

47.8^†

31.8^†

136

128

25.7^†

11.7^†

By treatment

ETN +MTX (n=220)

MTX alone (n=197)

71.4^†

49.2^†

54.1^†

32.5^†

194

172

25.3^†

12.2^†

COMET亚分析_极早期RA vs早期RA

Emery P, et al. EULAR 2011. Present No: AB0439.

背景: 类风湿关节炎(RA)新的ACR/EULAR缓解标准要求达到0或1个肿胀关节数(SI),并且简化的疾病活动指数(SDAI)积分≤3.3。COMET试验（MTX和ETN联合应用治疗早期活动性RA）证实MTX单用或与依那西普（ETN）联用治疗早期RA患者能减少疾病活动度。事后比较亚分析提示极早期RA患者（VERA，≤4月）与早期RA（ERA，4月-24月）相比疗效更好。

目标：本分析数据来自COMET研究，检测了ERA和VERA患者治疗52周时达到≤1 SJ, SDAI (≤3.3) 和 DAS28 (≤2.6) 缓解的比例。

方法：总体研究方法以往已经报道。本研究分析中，所观察的数据来自COMET研究（NCT00195494），对ERA或VERA患者根据不同治疗组评价治疗52周时的基线时间效应。52周前因为无效而停药的患者被视为无反应者。

结果：研究入组时患者平均肿胀关节数为17。治疗52周时，ERA患者接受ETN+MTX治疗比单用MTX治疗达到≤1 SJ的比例明显提高（70% vs. 46%, P<0.0001,见表）。尽管差异不显著，但VERA患者中接受联合治疗的达到≤1 SJ的比例也比MTX单用的多（75% vs. 59%, P=0.0853）。联合治疗组患者达到SDAI缓解的比例高于MTX单用组。然而，由于VERA患者例数太少，该统计学差异仅显示在ERA患者中。在VERA 患者中，达到≤1 SJ的患者绝大部分也同时达到DAS28缓解（ETN+MTX 85%，MTX单用55%），而≤1 SJ的患者中该比例分别为25%和5%。这种倾向同样见于ERA患者，接受ETN+MTX或单用MTX治疗达到≤1 SJ的患者同时获得DAS28缓解的比例分别为64%和60%，而≤1 SJ的患者中则为11%和8%。

*不管 SJ 数; ^†P (疗效) <0.05; ^‡ DAS28 缓解定义为 <2.6; ^§ 并非所有患者记录有计算SDAI的数据;**SDAI缓解定义为≤3.3.

结论：按照EULAR建议，治疗应获得尽可能低的疾病活动度。本研究中,VERA和ERA患者接受ETN + MTX联合治疗与单用MTX相比，52周时获得缓解（DAS28和SDAI）以及≤1 SJ的比例更高。经过一年治疗后,近3/4联合治疗的患者达到≤1 SJC且大部分获得缓解，支持早期干预的必要性。

附表

表：根据患者和治疗分组在52周时取得≤1 SJ或缓解的情况

根据患者分组

患者分组

治疗