对接受抗 TNF 药物或传统 DMARDs 治疗应答不足的活动期类风湿关节炎患者用利妥昔单抗治疗应答的预测因子。
Predictors of response to rituximab in patients with active rheumatoid arthritis and inadequate response to anti-TNF agents or traditional DMARDs.
机构信息
Department of Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain.
出版信息
Clin Exp Rheumatol. 2011 Nov-Dec;29(6):991-7. Epub 2011 Dec 22.
OBJECTIVES
Identifying early predictors of response to biological agents is important for both the individual patient and health economics. The aim here was to identify clinical variables that are easily assessed in clinical practice which are associated with a major response to rituximab (moderate to good EULAR response, according to DAS28 values) in patients with active rheumatoid arthritis and inadequate response to anti-TNF agents or traditional DMARDs.
METHODS
Rituximab (2x1g, two weeks apart) was administered to 108 patients in four different Spanish hospitals. The primary efficacy endpoint was the percentage of patients who achieved a major response at six months. Potential predictors of a major response were identified using multivariate binary logistic regression models.
RESULTS
At six months of treatment 75.9% of patients achieved a major response (24% good and 52% moderate). Comparing the clinical features at baseline between patients who did or did not achieve a major response, significant differences were found in rheumatoid factor (RF) and anti-CCP positivity, as well as in the number of failed anti-TNF agents prior to rituximab. While rituximab delivers clinical benefit in seronegative patients, the presence of RF and/or anti-CCP consistently enriches clinical responses. The multivariate analysis showed that the best model for predicting a major EULAR response to rituximab was comprised of the following two variables: the anti-CCP antibody positivity (p=0.045) and the number of previous anti-TNF agents used (p=0.028). Using a cut-off level for CCP of 300 U/ml we found that patients with an anti-CCP titre >300 U/ml were 3-4 times more likely to achieve a major EULAR response [odds ratio (OR): 3.38; 95% CI: 1.025-11.17]. By contrast, those patients who had failed to respond to 2 or more anti-TNF agents had a 72.5% lower probability of achieving a moderate to good EULAR response (OR: 0.275; 95% CI: 0.087-0.871) than did patients who had only failed to respond to one such agent.
CONCLUSIONS
A lower number of previously-failed TNF blockers and high anti-CCP titre can help select the best candidates for RTX therapy in patients with RA.
目的
识别生物制剂应答的早期预测因子对于个体患者和卫生经济学都很重要。本研究旨在确定在接受利妥昔单抗治疗的活动期类风湿关节炎患者中，哪些临床变量容易在临床实践中评估，且与利妥昔单抗的主要应答（根据 DAS28 值判断为中度至良好的 EULAR 应答）相关，这些应答与抗 TNF 药物或传统 DMARDs 治疗反应不佳相关。
方法
在西班牙的四家医院中对 108 名患者给予利妥昔单抗（2x1g，间隔两周）治疗。主要疗效终点是治疗 6 个月时达到主要应答（24%为良好应答，52%为中度应答）的患者比例。使用多变量二项逻辑回归模型确定主要应答的潜在预测因子。
结果
在治疗 6 个月时，75.9%的患者达到了主要应答（24%为良好应答，52%为中度应答）。比较达到和未达到主要应答患者的基线临床特征，发现类风湿因子（RF）和抗 CCP 阳性率以及在接受利妥昔单抗治疗前使用的抗 TNF 药物数量存在显著差异。虽然利妥昔单抗可给血清阴性患者带来临床获益，但 RF 和/或抗 CCP 的存在始终可增强临床应答。多变量分析显示，预测利妥昔单抗治疗后达到主要 EULAR 应答的最佳模型包括以下两个变量：抗 CCP 抗体阳性（p=0.045）和使用的先前抗 TNF 药物数量（p=0.028）。使用 CCP 截值 300 U/ml，我们发现 CCP 滴度>300 U/ml 的患者达到主要 EULAR 应答的可能性增加 3-4 倍[比值比（OR）：3.38；95%置信区间（CI）：1.025-11.17]。相比之下，与仅对 1 种抗 TNF 药物治疗反应不佳的患者相比，对 2 种或更多抗 TNF 药物治疗反应不佳的患者达到中度至良好 EULAR 应答的可能性低 72.5%（OR：0.275；95%CI：0.087-0.871）。
结论
先前失败的 TNF 阻滞剂数量较少和高 CCP 滴度可帮助选择类风湿关节炎患者中接受 RTX 治疗的最佳候选者。
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