ACR2010_TEAR研究的2年放射学结局

之前TEAR研究结果显示以DAS28评估的2年临床疗效无甚差异。本次初步分析显示依那西普联合甲氨蝶呤(ETN + MTX)的放射学结局优于传统DMARDS联合治疗(TT)，而且起始就联合依那西普或上台阶加用依那西普对放射学的抑制作用相仿。

原文

译文

[1368] - Two-Year Radiographic Results from the TEAR Trial.

Larry W Moreland, MD ¹,James R O'Dell, MD²,Harold E Paulus,Jeffrey R Curtis, MD, MPH³,Joan M Bathon, MD⁴,E. William St. Clair, MD⁵,S Louis Bridges, MD, PhD⁶,Xiao Zhang, PhD⁷,George Howard, DrPh⁷,Desiree M Van Der Heijde, MD, PhD,Stacey S Cofield, PhD⁷,for The TEAR Trial Investigators. ¹Rheumatology & Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA,²Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE,³,⁴Rheumatology & Immunology, University of AL Brimingham, Birmingham, AL,⁵Div of Rheumatology, Johns Hopkins Univ Ste, Baltimore, MD,⁶Duke University,⁷Clinical Immunology & Rheum, Univ of Alabama-Birmingham, Birmingham, AL,⁸The University of Alabama at Birmingham,⁹,¹⁰

Statement of Purpose: To describe radiographic results of the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) Trial, two-year, longitudinal, multi-center, randomized clinical trial that enrolled 755 early rheumatoid arthritis (RA) participants, comparing immediate combination treatment groups versus step-up from methotrexate (MTX) alone.

TEAR研究的2年放射学结局

 

Moreland LW, et al. ACR 2010. Present No: 1368.

 

目的：研究早期进展性类风湿关节炎治疗（TEAR）试验的放射学结局，这是一个为期2年的纵向、多中心、随机临床试验，纳入755例早期RA患者，将直接联合治疗组和从单用甲氨蝶呤（MTX）上阶梯治疗组进行比较。

 

Methods: Participants that were enrolled in TEAR from 2004-2007 with early RA (≤3 years). In addition to demographic and clinical measures, hand/foot radiographs were obtained at weeks 0, 48 and 102 and scored using the modified Sharp/van der Heijde scoring system.
Results: A total of 755 participants were enrolled in TEAR with 476 (63%) completing 102 weeks. As of June 2010: 474 (99.6%) baseline films and 297 completed films sets have been scored (62% of all completers). At baseline, the mean radiographic score was 6.2±15.0 units (median 2, IQR 0.5-6.0) and 22.2% had no damage (p = 0.30 by treatment group); 25.7% had no erosions, 66.9% had no joint space narrowing (p = 0.15 by group). The 297 with week 0 and 102 scores had a mean baseline score 5.4±12.7 (median 2, IQR 0.5-6.0, similar to entire cohort, p = 0.11); 19.5% had no damage.

方法：2004-2007年将早期RA（≤3年）患者纳入TEAR研究。除人口学和临床数据外，在第0、48、102周进行手、足放射学检查，采用改良的van der Heijde改良Sharp评分系统进行评分。

结果：TEAR研究共纳入755例患者，其中476例（63%）完成102周随访。在2010年6月，474例（99.6%）进行基线期评分，297例（占所有完成者的62%）完成末次评分。在基线期，平均放射学评分为6.2±15.0（中位值2，IQR 0.5-6.0），22.2%没有X线损害；25.7%没有侵蚀性病变，66.9%没有关节腔狭窄。在完成了第0周和第102周评分的297例患者中，平均基线期评分为5.4±12.7（中位值2，IQR 0.5-6.0，与整体队列相似，p = 0.11）；19.5%没有损害。

表. 用完成者分析法检测放射学平均进展（N=297）

 

		观察值 均值±SD (无X线损害的百分比)		校正基线后 第102周与第0周的差值
治疗组	例数	0周	102周	均值±SD	95%CI	P值
IE	105	7.2±19.8 (21.9)	7.9±20.5 (11.5)	0.6±4.2	-0.6, 1.7	0.6884
IT	45	4.4±5.5 (17.8)	7.1±14.8 (11.4)	2.7±12.6	0.9, 4.5
SE	106	4.1±5.6 (20.8)	4.7±6.1 (8.0)	0.6±2.1	-0.6, 1.8
ST	41	5.3±7.2 (12.2)	7.4±10.1 (4.0)	2.1±6.4	0.2, 4.0
ETN+MTX	211	5.7±14.5 (21.3)	6.2±15.2 (9.7)	0.6±3.3	-0.2, 1.4	0.0180
TT	86	4.9±6.3 (15.1)	7.3±12.7 (7.7)	2.4±10.1	1.1, 3.
起始联合(I)	150	6.4±16.8(20.7)	7.6±19.0(11.5)	1.6±7.7	0.6, 2.6	0.8059
上台阶(S)	147	4.5±6.1(18.4)	5.4±7.5 (6.7)	1.4±3.9	0.4, 2.5
所有患者	297	5.4±12.7 (19.5)	6.6±14.5 (14.5)	1.1±6.1	0.4, 1.8	NA

 

 

At week 102, the completers cohort had a mean score 6.5±14.5 (median 3, IQR 1.0-7.5), 9.1% had no damage; 10.8% with no erosions, 40.3% with no joint space narrowing. The mean increase from week 0 to 102 was 1.1±6.1 (median 0, IQR 0-1.0) and was not different across the four groups (p=0.69). When only treatment is considered, pooling the two etanercept (ETN) groups and the two triple therapy (TT) groups, to assess main effects, there was a significant difference between those receiving ETN + MTX and TT (increase of 0.6 vs 2.4, respectively; p=0.02). There was no difference by the timing of treatment (immediate versus step-up, p=0.81). The difference between ETN + MTX and TT was also observed in the subgroup of individuals with baseline radiographic damage score > 0 (increase of 0.6 vs 2.8, p=0.02). There was no change at week 102 among patients with no damage at week 0. In addition, 71.4% of participants achieved radiographic remission (change ≤ 0.5), which was not different by the timing or type of treatment. The remaining 38% of x-rays for trial completers are in the process of being scored.

Conclusions: While prior TEAR results showed no significant differences in clinical findings as assessed by DAS28, this preliminary analysis showed that treatment with ETN + MTX resulted in statistically significant radiographic benefit over TT, regardless of timing of treatment. All results to be updated to the full 476 completion cohort.

    在第102周，完成者队列平均评分为6.5±14.5（中位值3，IQR 1.0-7.5），9.1%没有损害；10.8%没有侵蚀性病变，40.3%没有关节间隙狭窄。从第0周到第102周，评分平均增加1.1±6.1（中位值0，IQR 0-1.0），四组之间没有差别（p=0.69）。如果仅考虑治疗方法，合并2个依那西普（ETN）组和2个三联治疗（TT）组，ETN+MTX与TT患者之间有显著性差异（分别增加0.6和2.4，p=0.02）。如果考虑治疗时机，直接治疗与上阶梯治疗之间没有差异（p=0.81）。在基线期放射学损害评分>0的亚群中，ETN+MTX与TT患者有显著性差异（分别增加0.6和2.8，p=0.02）。第0周没有损害的患者在第102周没有变化。71.4%患者达到放射学缓解（变化≤ 0.5），这在治疗时机或治疗方法等方面没有差别。余下38%试验完成者的X线片仍在评分中。

结论：之前TEAR研究结果显示以DAS28评估的2年临床疗效无甚差异。本次初步分析显示依那西普联合甲氨蝶呤(ETN + MTX)的放射学结局优于传统DMARDS联合治疗(TT)，而且起始就联合依那西普或上台阶加用依那西普对放射学的抑制作用相仿。在完成所有476例患者评估后将对分析结果进行更新。