Aletaha Daniel, Funovits Julia, Keystone Edward C, Smolen Josef S
Medical University of Vienna, Vienna, Austria.
Arthritis Rheum. 2007 Oct;56(10):3226-35. doi: 10.1002/art.22943.
To assess whether disease activity levels at treatment initiation or during the first 3 months of therapy predict disease activity at 1 year after treatment initiation.
Pooled patient data from early rheumatoid arthritis (RA) clinical trials (n = 1,342) of methotrexate (MTX), tumor necrosis factor (TNF) inhibitor monotherapy (adalimumab and etanercept), and the combination of the two (adalimumab or infliximab plus MTX) were used for the primary analyses. Pooled data from clinical trials of MTX and of TNF inhibitor plus MTX in late RA (n = 712) were used for validation of the results. Disease activity was primarily assessed using the Simplified Disease Activity Index (SDAI); in addition, we calculated the Disease Activity Score 28-joint assessment (DAS28) and the Clinical Disease Activity Index (CDAI). Associations of disease activity measures at baseline and at 1, 2, 3, and 6 months with disease activity values or disease activity states at 1 year were performed using Spearman's rank correlation, analysis of variance, and diagnostic testing procedures, including receiver operating characteristic (ROC) curve analyses, and probit analysis.
Correlations with SDAI values at end point were significant (P < 0.0001) at baseline, and increased to r = approximately 0.6 at 3 months. The area under the ROC curve indicated a high diagnostic test yield with respect to the 1-year outcome (area under the ROC curve approximately 0.8). At all time points, including baseline, the group of patients who achieved remission at 1 year had lower average SDAI values than did those whose disease activity was high at 1 year. The groups achieving low or moderate disease activities at 1 year had SDAI values lying between. Baseline disease activity was less associated with disease activity at the end point for treatment with TNF inhibitor plus MTX, indicating its effectiveness over a broader range of baseline disease activity, but the association with end point disease activity was similar to that in the MTX treatment group at 1 month after treatment initiation. The data were similar when scores on the DAS28 and CDAI were used and were fully validated in the independent cohort of patients with late RA.
The level of disease activity at baseline and especially during the first 3 months of treatment is significantly related to the level of disease activity at 1 year. Patients who reach a moderate or low disease activity status after 3-6 months of therapy may require switching to alternative therapies. Our findings indicate that intensive and dynamic treatment strategies that include a closer look at disease activity at 3 months in patients with early and late RA is warranted.
评估治疗开始时或治疗的前3个月内的疾病活动水平是否可预测治疗开始后1年时的疾病活动情况。
将来自甲氨蝶呤（MTX）、肿瘤坏死因子（TNF）抑制剂单药治疗（阿达木单抗和依那西普）以及两者联合治疗（阿达木单抗或英夫利昔单抗加MTX）的早期类风湿关节炎（RA）临床试验（n = 1342）的汇总患者数据用于主要分析。将MTX以及TNF抑制剂加MTX治疗晚期RA的临床试验（n = 712）的汇总数据用于结果验证。主要使用简化疾病活动指数（SDAI）评估疾病活动；此外，我们还计算了28个关节疾病活动评分（DAS28）和临床疾病活动指数（CDAI）。使用Spearman等级相关性分析、方差分析以及诊断测试程序，包括受试者工作特征（ROC）曲线分析和概率分析，来分析基线、第1、2、3和6个月时的疾病活动测量值与1年时的疾病活动值或疾病活动状态之间的关联。
基线时与终点SDAI值的相关性显著（P < 0.0001），在3个月时增加到r约为0.6。ROC曲线下面积表明对于1年结局具有较高的诊断测试效能（ROC曲线下面积约为0.8）。在所有时间点，包括基线，1年时达到缓解的患者组的平均SDAI值低于1年时疾病活动度高的患者组。1年时达到低或中度疾病活动度的组的SDAI值介于两者之间。对于TNF抑制剂加MTX治疗，基线疾病活动与终点疾病活动的相关性较小，表明其在更广泛的基线疾病活动范围内有效，但与终点疾病活动的相关性与治疗开始后1个月时MTX治疗组相似。当使用DAS28和CDAI评分时数据相似，并且在晚期RA患者的独立队列中得到了充分验证。
基线时尤其是治疗的前3个月内的疾病活动水平与1年时的疾病活动水平显著相关。治疗3 - 6个月后达到中度或低度疾病活动状态的患者可能需要改用其他治疗方法。我们的研究结果表明，对于早期和晚期RA患者，有必要采取强化和动态的治疗策略，包括密切关注3个月时的疾病活动情况。
