Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taichung, Taiwan Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan.
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taichung, Taiwan.
Ann Rheum Dis. 2015 Mar;74(3):e16. doi: 10.1136/annrheumdis-2013-203893. Epub 2014 Jan 17.
To evaluate the associations between (1) antidrug antibody (ADAb) and therapeutic response, (2) ADAb and serum drug trough levels and (3) serum drug levels and therapeutic responses in rheumatoid arthritis (RA) patients receiving adalimumab or etanercept. Secondarily, we aim (1) to evaluate the concordance between radioimmunoassay and bridging ELISA for ADAb assessment and to evaluate the correlation between two different ELISA methods for detecting drug levels, and (2) to determine the optimal cut-off drug levels for good European League Against Rheumatism (EULAR) response.
ADAb levels were determined by bridging ELISA and radioimmunoassay, and drug levels evaluated using sandwich ELISA among 36 adalimumab-treated patients and 34 etanercept-treated patients at the 6th and 12th month. The optimal cut-off drug levels for EULAR responses were determined by receiver-operating characteristic curve analysis.
ADAb was detected in 10 (27.8%) and 13 (36.1%) of adalimumab-treated patients after 12-month therapy using bridging ELISA and radioimmunoassay respectively, but not detected in any of etanercept-treated patients. The presence of ADAb was associated with lower EULAR response and lower drug levels compared with those without ADAb (both p<0.001). Drug trough levels were positively associated with DAS28 decrement (ΔDAS28) (all p<0.001). The optimal cut-off trough levels for adalimumab were 1.274 μg/mL and 1.046 μg/mL, and those for etanercept were 1.242 μg/mL and 0.800 μg/mL for good EULAR response assessed at the 6th and 12th month, respectively.
ADAb levels were inversely correlated with therapeutic response and drug levels. The positive correlation between drug levels and ΔDAS28 indicates that drug monitoring would be useful to evaluate therapeutic response of TNF-α inhibitors.
评估（1）抗药物抗体（ADAb）与治疗反应之间、（2）ADAb 与血清药物谷浓度之间以及（3）血清药物浓度与接受阿达木单抗或依那西普治疗的类风湿关节炎（RA）患者的治疗反应之间的关系。其次，我们旨在（1）评估用于 ADAb 评估的放射免疫分析和桥接 ELISA 之间的一致性，并评估用于检测药物水平的两种不同 ELISA 方法之间的相关性，以及（2）确定良好的欧洲抗风湿病联盟（EULAR）反应的最佳药物浓度截断值。
在第 6 个月和第 12 个月时，通过桥接 ELISA 和放射免疫分析测定 36 例阿达木单抗治疗患者和 34 例依那西普治疗患者的 ADAb 水平，并通过夹心 ELISA 评估药物水平。通过受试者工作特征曲线分析确定 EULAR 反应的最佳药物浓度截断值。
在接受 12 个月治疗后，使用桥接 ELISA 和放射免疫分析分别在 10（27.8%）和 13（36.1%）例阿达木单抗治疗患者中检测到 ADAb，但在任何依那西普治疗患者中均未检测到 ADAb。与无 ADAb 的患者相比，ADAb 的存在与较低的 EULAR 反应和较低的药物水平相关（均 p<0.001）。药物谷浓度与 DAS28 降低（ΔDAS28）呈正相关（均 p<0.001）。阿达木单抗的最佳谷浓度截断值分别为 1.274 μg/mL 和 1.046 μg/mL，依那西普的最佳谷浓度截断值分别为 1.242 μg/mL 和 0.800 μg/mL，分别用于评估第 6 个月和第 12 个月时的良好 EULAR 反应。
ADAb 水平与治疗反应和药物水平呈负相关。药物水平与 ΔDAS28 之间的正相关表明药物监测有助于评估 TNF-α 抑制剂的治疗反应。
