体现临床实际基线疾病活动度的早期RA患者中， 治疗起效时间对临床和放射学的影响

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Clinical and Radiographic Implications of Time to Treatment Response in Early Rheumatoid Arthritis Patients with Baseline Levels of Disease Activity Reflective of a Clinical Practice Setting   Edward Keystone 1, Michael E. Weinblatt2, Boulos Haraoui3, Benoit Guerette4, Neelufar Mozaffarian5, Shufang Liu5, Benjamin Wolfe5 and Arthur Kavanaugh6, 1University of Toronto, Toronto, ON, 2Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 3Institut de Rhumatologie, Montreal, QC, 4Abbott, Rungis, France, 5Abbott, Abbott Park, IL, 6University of California San Diego, San Diego, CA   Presentation Number: 417   Background/Purpose: A retrospective analysis of the PREMIER trial demonstrated that in early RA patients (pts) on methotrexate (MTX) both the timing and magnitude of a clinical response determines long-term outcomes. Cohort data reveal that the baseline (BL) disease activity of pts in clinical trials is often more severe than that in clinical practice. This study aimed to evaluate the association of clinical responses occurring by 12 weeks (wks) or 24 wks with long-term outcomes in MTX-treated pts from PREMIER who had BL levels of disease activity more closely resembling those observed in “real world” practice. Method: In this post hoc analysis, observed data from MTX-pts in PREMIER who had BL DAS28(CRP) ≤6.0 were evaluated in the context of the total MTX population [mean DAS28(CRP) =6.3]. Pts were categorized as early- or delayed-responders (R) based on clinical measures [50%/70% improvement in ACR response criteria or improvement in DAS28(CRP) >1.2] at 12 and 24 wks: early-R achieved the clinical target by wk 12 and maintained it at wk 24; delayed-R did not achieve the target at wk 12 but met it by wk 24. Long-term outcomes for early- and delayed-R were the percentage in DAS28(CRP) remission (<2.6) or with rapid radiographic progression [RRP, ΔmTSS >3) at 52 wks; odds ratios (95% CI) were used to compare outcomes of early- and delayed-R. Results: A total of 72 of the 199 evaluable MTX-pts had BL DAS28(CRP) ≤6.0 [mean (SD) DAS28(CRP) =5.5 (0.4)]. The percentages of pts who achieved early and delayed responses were 29.2% and 27.8% for ACR50, 13.9% and 18.1% for ACR70, and 58.8% and 22.1% for DAS28(CRP) improvement >1.2; all percentages were comparable with those in the total MTX population. Long-term outcomes were somewhat better for pts with lower DAS28(CRP) at BL, although the trends observed in the overall population remained: early-R, irrespective of the magnitude of the response, had better clinical and radiographic outcomes at wk 52 (Table). Delayed-R with an ACR50 or improvement in DAS28(CRP) >1.2 had significantly reduced odds of achieving remission at wk 52. In fact, pts with delayed responses needed to reach an ACR70 by wk 24 to have comparable odds of reaching remission at wk 52. Delayed-R, regardless of the magnitude of response, also had a high proportion of RRP at wk 52. Indeed, pts with delayed ACR70 responses had an RRP prevalence of >30%. Conclusion: MTX-pts with lower BL DAS28(CRP) achieved somewhat better clinical and radiographic outcomes at wk 52 than the overall MTX-population. Still, pts who did not achieve a strong clinical response by wk 12 had a lower likelihood of achieving remission and were at increased risk of developing RRP compared with early-R. Therefore, these data lend support to the applicability of the findings in PREMIER to pts with lower BL disease activity, a population that may be more reflective of RA pts typically seen in a rheumatology clinic.	体现临床实际基线疾病活动度的早期RA患者中， 治疗起效时间对临床和放射学的影响 Edward Keystone , et al. ACR 2011. Present No: 417   背景/目的:PREMIER临床试验回顾性分析表明, 早期RA患者接受甲氨蝶呤(MTX)治疗，其长期预后受MTX治疗的时机和长期疗效的影响。队列数据显示,临床试验中患者基线(BL)水平的疾病活动度往往比实际临床的患者要高。该研究目的是评价PREMIER试验中BL疾病活动度接近实际临床的MTX治疗患者，12周或24周临床疗效与长期预后的相关性。 方法:本研究采用post hoc分析,观察数据来自PREMIER试验中BL水平DAS28(CRP) ≤6.0的MTX治疗患者（该研究中总的MTX患者平均DAS28(CRP)= 6.3)。根据12周和24周时临床指标［ACR50/70标准或DAS(CRP)> 1.2]将患者分为早期有效和延期有效(R)：早期有效即12周达到治疗目标并维持道24周，延迟有效为12周未达标但在24周时达标。长期预后指52周时达到DAS28(CRP)缓解(p < 2.6)或影像学快速进展[RRP, ΔmTSS > 3)的患者比率，比较两组患者的风险比(95% CI)。 结果:199例MTX治疗患者中有72例BL(CRP) ≤ 6.0(平均(SD)DAS28 (CRP)= 5.5(0.4)]。获得早期有效和延迟有效的患者比率分别为ACR50 29.2%和27.8%、ACR7013.9%和18.1%, DAS28(CRP)改善>1.2 58.8%和22.1%;所有的比例与总的MTX治疗人群相当。BL时DAS28(CRP)水平低的患者一定程度上长期结果要好一些, 尽管在总的观察人群中的趋势是：早期有效患者在52周时临床和放射学结局更好（表5）。延迟有效的患者在52周时获得ACR50或DAS28(CRP)>1.2的可能性显著减少。事实上,延期有效的患者在24周时达到ACR70才能有相似的机会获得52周缓解。不论疗效多少，延迟有效患者在52周时也有高比例的RRP。事实上,延迟获得ACR70反应患者发生RRP比率 > 30%。 结论:BL时DAS(CRP)低的MTX治疗患者通常能在52周获得更好的临床和影像学结果。同时,与早期有效患者相比，12周时未能获得明显临床疗效的患者达到临床缓解的概率较低且出现RRP机率较高。因此,这些数据支持PREMIER试验中低BL疾病活动度的患者结果在风湿病临床实践中的适用性，因为该群患者可能更反应日常实践中典型病例。