Brandt J, Listing J, Sieper J, Rudwaleit M, van der Heijde D, Braun J
Department of Gastroenterology/Rheumatology, Charité, Berlin, Germany.
Ann Rheum Dis. 2004 Nov;63(11):1438-44. doi: 10.1136/ard.2003.016717. Epub 2004 Mar 25.
To develop and compare candidate improvement criteria for anti-TNFalpha treatment in ankylosing spondylitis with optimal discriminating capacity between treatment and placebo.
Data from two randomised controlled trials which included 99 patients treated with infliximab or etanercept were used to evaluate 50 candidate improvement criteria. These were developed on the basis of pain, patient's global assessment, function, morning stiffness, spinal mobility, and C reactive protein. Different levels of improvement in each domain (20-60%) were used to define Boolean type criteria. These criteria were compared with different percentages of improvement on the BASDAI and with modified ASAS improvement criteria. Bootstrap methods were applied to calculate 95% confidence intervals (CI) of the chi(2) test values to select the best candidate improvement criteria.
The best performing improvement criteria were "20% improvement in five of six domains" (chi(2) = 31.9 (95% CI, 18.0 to 46.9)) with a low placebo response of 2.9% and a high response to infliximab of 67.7%; and "ASAS 40% improvement" (chi(2) = 26.5 (13.3 to 41.1)), with response to placebo of 5.7% and response to infliximab of 64.7%. The good discriminating capacity of the two improvement criteria was confirmed by the combined dataset of the infliximab and etanercept trial.
The "five of six" improvement criterion has the advantage of including the objective domains spinal mobility and acute phase reactants, but requires only 20% improvement. The ASAS 40% improvement criterion has the advantage of setting a high threshold, but only in patient reported outcomes. The choice between these improvement criteria needs to be based on further validation from upcoming trials.
制定并比较强直性脊柱炎抗TNFα治疗的候选改善标准，使其在治疗组与安慰剂组之间具有最佳鉴别能力。
来自两项随机对照试验的数据（其中包括99例接受英夫利昔单抗或依那西普治疗的患者）用于评估50项候选改善标准。这些标准基于疼痛、患者整体评估、功能、晨僵、脊柱活动度和C反应蛋白制定。每个领域不同程度的改善（20%-60%）用于定义布尔型标准。将这些标准与BASDAI不同百分比的改善情况以及改良的ASAS改善标准进行比较。应用自助法计算卡方检验值的95%置信区间（CI），以选择最佳候选改善标准。
表现最佳的改善标准为“六个领域中的五个领域改善20%”（卡方 = 31.9（95%CI，18.0至46.9）），安慰剂反应率低至2.9%，英夫利昔单抗反应率高达67.7%；以及“达到ASAS 40%改善”（卡方 = 26.5（13.3至41.1）），安慰剂反应率为5.7%，英夫利昔单抗反应率为64.7%。英夫利昔单抗和依那西普试验的合并数据集证实了这两项改善标准具有良好的鉴别能力。
“六个中的五个”改善标准的优点是纳入了客观领域脊柱活动度和急性期反应物，但仅需20%的改善。ASAS 40%改善标准的优点是设定了较高阈值，但仅适用于患者报告的结局。这些改善标准之间的选择需要基于即将开展的试验的进一步验证。
