Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients
Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients
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DOI：
10.1002/art.22943
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发表时间：
2007-10-01
影响因子：
--
通讯作者：
Smolen, Josef S.
中科院分区：
文献类型：
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作者：
Aletaha, Daniel;Funovits, Julia;Smolen, Josef S.
Objective.评估治疗开始时或治疗前3个月的疾病活动水平是否可预测治疗开始后1年的疾病活动。主要分析使用了来自甲氨蝶呤（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西单抗加MTX）的早期类风湿性关节炎（RA）临床试验（n = 1，342）的汇总患者数据。MTX和TNF抑制剂加MTX治疗晚期RA（n = 712）的临床试验汇总数据用于验证结果。主要使用简化疾病活动指数（SDAI）评估疾病活动;此外，我们还计算了疾病活动评分28-关节评估（DAS 28）和临床疾病活动指数（CDAI）。采用斯皮尔曼等级相关、方差分析和诊断测试程序（包括受试者工作特征（ROC）曲线分析和概率分析），对基线和第1、2、3和6个月时的疾病活动性指标与第1年时的疾病活动性值或疾病活动性状态进行相关性分析。基线时与终点SDAI值的相关性显著（P < 0.0001），3个月时增加至r = 0.6。ROC曲线下面积表明，相对于I年结果，诊断测试产率较高（ROC曲线下面积类似于0.8）。在所有时间点，包括基线，在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。在第一年达到低或中度疾病活动的组的SDAI值介于两者之间。TNF抑制剂联合MTX治疗的基线疾病活动与终点疾病活动的相关性较低，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MTX治疗组在治疗开始后1个月的相关性相似。当使用DAS 28和CDAI评分时，数据相似，并在晚期RA患者的独立队列中得到充分验证。基线时，尤其是治疗前3个月的疾病活动水平与第1年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转换为替代疗法。我们的研究结果表明，强化和动态的治疗策略，包括在3个月内密切关注早期和晚期RA患者的疾病活动是必要的。
Objective. To assess whether disease activity levels at treatment initiation or during the first 3 months of therapy predict disease activity at I year after treatment initiation.Methods. 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 I 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.Results. Correlations with SDAI values at end point were significant (P < 0.0001) at baseline, and increased to r = similar to 0.6 at 3 months. The area under the ROC curve indicated a high diagnostic test yield with respect to the I-year outcome (area under the ROC curve similar to 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 I 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 I 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.Conclusion. 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 I 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.