Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay - RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.

中文翻译：

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类风湿关节炎的个性化药物：免疫原性如何影响TNF抑制剂的使用。

接受肿瘤坏死因子α抑制剂（TNFi）治疗的患者中，多达40％对治疗无反应。测试药物的生物利用度和/或抗药物抗体（ADAb）的水平可以证明调整剂量或切换到其他药物的合理性，从而实现个性化的药物治疗方法。我们报告了针对药物/ ADAb检测的不同方法[ELISA和基于细胞的功能测定（报告基因测定-RGA）]，以及药物生物利用度与ADAb之间关系的多中心横断面研究。测试了用英夫利昔单抗（IFX; n = 67），阿达木单抗（ADL; n = 49）或依那西普（ETA; n = 47）治疗的163名类风湿关节炎（RA）患者的药物和ADAb水平。此外，我们报告了另外70名患者（59名RA和11名青少年特发性关节炎-JIA）在基线（T0）以及仅用ADL或ETA治疗3（T3）和6个月（T6）后接受药物和ADAb水平测试的前瞻性数据。由于IFX生物仿制药的使用增加，未包括IFX治疗的患者。为了避免两项研究均使用不必要的变量，使用了严格的纳入标准。在研究之前，没有患者使用TNFi，并且仅将TNFi与甲氨蝶呤联用。根据EULAR反应标准定义临床反应。在比较研究中，两种测定法进行了比较。因此，由于其在临床环境中的可行性，因此选择ELISA进行前瞻性研究。这项横断面研究仅在IFX和ADL治疗组中发现了ADAb，与血液中药理学药物供应减少有关。在前瞻性研究中发现了ADL治疗组的可比结果，该结果也显示了药物/ ADAb水平与临床反应丧失之间的关系。我们的发现总共支持现实世界临床环境中的药物和抗药物Ab监测，从而实现个性化治疗并减少慢性炎症性关节炎的残疾。