Division of Rheumatology Department of Internal Medicine 3, Medical University of Vienna and Hietzing Hospital, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
University of Texas Southwestern, Dallas, TX, USA.
Arthritis Res Ther. 2019 Nov 10;21(1):231. doi: 10.1186/s13075-019-2005-9.
The ACR20 has been validated as the best discriminator of efficacy in placebo-controlled trials, but not in head-to-head trials comparing effective therapies in patients with rheumatoid arthritis (RA). We assessed the most discriminatory ACR response and most discriminatory percent improvement in disease activity measures for Simplified Disease Activity index (SDAI), Clinical Disease Activity index (CDAI), and 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) using different patient populations and trial designs.
Data from two placebo-controlled studies in established RA and two head-to-head studies in early RA were analyzed. The numeric ACR response for each treatment and P value for the difference between treatments were calculated at multiple time points to determine the ACR response associated with the lowest P value. Similarly, values for percent improvement from baseline in SDAI, CDAI, and DAS28(CRP) with the most discrimination between treatments were examined.
In the head-to-head early RA trials, the minimum P value and greatest treatment difference between the active comparator arms at 6 months was achieved at higher ACR rates and greater percent improvements in other disease activity measures. In established RA, lower responses (minimum P value and maximum treatment difference) and smaller improvements in disease activity scores had better discriminatory ability at 6 months.
The most discriminatory ACR response rate and percent improvement in disease activity measures were higher in head-to-head active comparator trials in early RA versus placebo-controlled trials in established RA. This difference should be considered in future clinical trial designs.
NCT00195663, NCT00420927, NCT00195702.
ACR20 已被验证为安慰剂对照试验中疗效的最佳判别指标，但在比较类风湿关节炎（RA）患者中有效治疗的头对头试验中并非如此。我们评估了简化疾病活动指数（SDAI）、临床疾病活动指数（CDAI）和基于 C 反应蛋白的 28 关节疾病活动评分（DAS28(CRP)）的最具判别力的 ACR 反应和疾病活动指标的最具判别力的百分比改善，使用不同的患者人群和试验设计。
对两项已确立的 RA 安慰剂对照研究和两项早期 RA 头对头研究的数据进行了分析。计算了每个治疗的数值 ACR 反应和治疗之间差异的 P 值，以确定与最低 P 值相关的 ACR 反应。同样，还检查了 SDAI、CDAI 和 DAS28(CRP) 从基线的百分比改善值，这些值在治疗之间具有最大的判别能力。
在早期 RA 的头对头试验中，在 6 个月时，活性对照臂之间的最小 P 值和最大治疗差异是通过更高的 ACR 率和其他疾病活动指标的更大百分比改善来实现的。在已确立的 RA 中，较低的反应（最小 P 值和最大治疗差异）和疾病活动评分的较小改善在 6 个月时有更好的判别能力。
与已确立的 RA 安慰剂对照试验相比，早期 RA 头对头活性对照试验中的最具判别力的 ACR 反应率和疾病活动指标的百分比改善更高。在未来的临床试验设计中应考虑到这种差异。
NCT00195663、NCT00420927、NCT00195702。
