Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Institute of Biomedical Science, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Institute of Microbiology and Immunology, Chung Shan Medical University,
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Institute of Biomedical Science, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University.
Rheumatology (Oxford). 2016 Jan;55(1):143-8. doi: 10.1093/rheumatology/kev298. Epub 2015 Aug 31.
To evaluate the impact of adalimumab (ADA) dose-halving on therapeutic responses and drug levels, the differences in drug levels among patients with different therapeutic responses and the optimal baseline cut-off ADA levels for predicting persistent remission or low disease activity (LDA) at week 24 of dose-halving therapy in 64 RA patients who had already achieved LDA or remission at baseline.
Anti-ADA antibody levels were determined by bridging ELISA, ADA levels were evaluated using sandwich ELISA and therapeutic responses were assessed by the 28-joint DAS change. The optimal cut-off drug levels for predicting persistent remission were determined by receiver operating characteristic curve analysis.
At baseline, 25 (39.1%) and 39 (60.9%) patients had achieved remission and LDA, respectively. After 24 week ADA dose-halving, persistent remission was observed in 23 patients, remission turned LDA in 2 patients, persistent LDA in 24 patients and disease flare in 15 (23.5%) patients. Three patients who developed anti-ADA antibodies at week 24 of dose-halving had very low drug levels and disease flare. Among 61 anti-ADA antibody-negative patients, ADA levels declined by half after 24 weeks of dose-halving (median 5.5 vs 2.6 μg/ml). Baseline ADA levels were significantly higher in patients with persistent remission (median 10.5 μg/ml) or LDA (4.5 μg/ml) than in those with disease flare (0.9 μg/ml), indicating associations of ADA levels with therapeutic responses. An ADA level above the cut-off value of 6.4 μg/ml might predict persistent remission after dose-halving with high sensitivity and specificity.
ADA dose-halving is feasible for patients who have achieved remission and sufficient drug levels. Drug level monitoring may help clinicians optimize the dosing regimen and prevent overtreatment for patients receiving anti-TNF-α therapy.
评估阿达木单抗（ADA）剂量减半对治疗反应和药物水平的影响，不同治疗反应患者之间药物水平的差异，以及预测剂量减半治疗 24 周时持续缓解或低疾病活动度（LDA）的最佳基线 ADA 水平 cutoff 值，纳入 64 例基线时已达到 LDA 或缓解的 RA 患者。
采用桥接 ELISA 检测抗-ADA 抗体水平，夹心 ELISA 检测 ADA 水平，28 关节 DAS 变化评估治疗反应。采用受试者工作特征曲线分析确定预测持续缓解的最佳药物水平 cutoff 值。
基线时，25（39.1%）和 39（60.9%）例患者分别达到缓解和 LDA。ADA 剂量减半治疗 24 周后，23 例患者持续缓解，2 例缓解转为 LDA，24 例患者持续 LDA，15 例（23.5%）患者疾病复发。ADA 剂量减半治疗 24 周时，3 例患者出现抗-ADA 抗体，且病情复发。61 例抗-ADA 抗体阴性患者，剂量减半 24 周后 ADA 水平下降一半（中位数 5.5 vs 2.6 μg/ml）。持续缓解（中位数 10.5 μg/ml）或 LDA（中位数 4.5 μg/ml）患者的基线 ADA 水平显著高于疾病复发（中位数 0.9 μg/ml）患者，提示 ADA 水平与治疗反应相关。ADA 水平高于 6.4 μg/ml 的 cutoff 值可能有助于预测剂量减半后持续缓解，且具有较高的敏感性和特异性。
对于已达到缓解且药物水平充足的患者，ADA 剂量减半是可行的。药物水平监测可能有助于临床医生优化给药方案，防止接受抗 TNF-α 治疗的患者过度治疗。
