Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands.
Ann Rheum Dis. 2015 Mar;74(3):513-8. doi: 10.1136/annrheumdis-2013-204172. Epub 2013 Dec 10.
To determine a concentration-effect curve of adalimumab in rheumatoid arthritis (RA) patients taking into account the effect of methotrexate (MTX) on concentration and effect and to identify a therapeutic range for adalimumab concentrations.
In a prospective observational cohort study, 221 consecutive patients with RA were treated with 40 mg adalimumab subcutaneously every other week. The relationship between adalimumab trough level and clinical efficacy after 28 weeks of follow-up was determined in a concentration-effect curve. A receiver-operator characteristics (ROC) curve established a therapeutic cut-off concentration. The effect of MTX on adalimumab trough levels was shown by dividing patients that are and are not concomitantly using MTX in the concentration-effect curve and a concentration table.
Clinical efficacy improved with increasing adalimumab concentration and reached a maximum (mean disease activity score in 28 joints improvement of 2) with levels between 5-8 μg/mL. Levels exceeding 8 μg/mL were illustrated to have no additional beneficial effect on disease activity. The ROC curve showed an area under the curve of 0.695 (95% CI 0.626 to 0.764) for European League Against Rheumatism response and adalimumab levels: good responders versus non-responders and moderate responders. A cut-off of 5 μg/mL had a sensitivity of 91% and a specificity of 43%. Adalimumab levels are influenced by concomitant MTX use: patients on adalimumab monotherapy had a median adalimumab level of 4.1 μg/mL (IQR 1.3-7.7), whereas patients concomitantly taking MTX had a median level of 7.4 μg/mL (IQR 5.3-10.6, p<0.001).
Adalimumab trough levels in a range of 5-8 μg/mL are sufficient to reach adequate clinical response. These levels are influenced substantially by concomitant MTX use.
确定接受甲氨蝶呤（MTX）治疗的类风湿关节炎（RA）患者中阿达木单抗的浓度-效应曲线，以确定阿达木单抗浓度的治疗范围。
在一项前瞻性观察队列研究中，221 例连续 RA 患者接受每 2 周皮下注射 40mg 阿达木单抗。在 28 周随访后的浓度-效应曲线中确定阿达木单抗谷浓度与临床疗效之间的关系。通过在浓度-效应曲线和浓度表中比较同时使用和不使用 MTX 的患者，建立了接受者操作特征（ROC）曲线以确定治疗性截止浓度。
阿达木单抗浓度增加与临床疗效改善相关，在 5-8μg/mL 之间达到最大（28 个关节疾病活动度评分改善均值为 2）。超过 8μg/mL 的浓度对疾病活动度没有额外的有益作用。ROC 曲线显示欧洲抗风湿病联盟反应和阿达木单抗水平的曲线下面积为 0.695（95%置信区间 0.626 至 0.764）：良好反应者与无反应者和中度反应者。5μg/mL 的截止值具有 91%的敏感性和 43%的特异性。阿达木单抗水平受同时使用 MTX 的影响：接受阿达木单抗单药治疗的患者中位阿达木单抗水平为 4.1μg/mL（IQR 1.3-7.7），而同时接受 MTX 治疗的患者中位水平为 7.4μg/mL（IQR 5.3-10.6，p<0.001）。
阿达木单抗谷浓度在 5-8μg/mL 范围内足以达到足够的临床反应。这些水平受同时使用 MTX 的影响很大。
