Istituto Auxologico Italiano, IRCCS, Experimental Laboratory of Immuno-rheumatology, Milan, Italy.
Rheumatology Department, ASST Gaetano Pini-CTO, Milan, Italy.
Autoimmun Rev. 2020 May;19(5):102509. doi: 10.1016/j.autrev.2020.102509. Epub 2020 Mar 12.
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.
高达 40%接受肿瘤坏死因子 α 抑制剂 (TNFi) 治疗的患者对治疗无反应。检测药物生物利用度和/或抗药物抗体 (ADAb) 水平可能证明需要调整剂量或改用不同的药物，从而实现个体化治疗。我们报告了一项关于不同方法 [ELISA 和基于细胞的功能测定 (报告基因测定 - RGA)] 用于药物/ADAb 检测的多中心横断面研究，以及药物生物利用度与 ADAb 之间的关系。我们对 163 例接受英夫利昔单抗 (IFX；n = 67)、阿达木单抗 (ADL；n = 49) 或依那西普 (ETA；n = 47) 治疗的类风湿关节炎 (RA) 患者进行了药物和 ADAb 水平检测。此外，我们还报告了另外 70 例患者 (59 例 RA 和 11 例幼年特发性关节炎 - JIA) 的前瞻性数据，这些患者在基线 (T0) 和仅接受 ADL 或 ETA 治疗 3 个月 (T3) 和 6 个月 (T6) 后进行了药物和 ADAb 水平检测。由于越来越多地使用 IFX 生物类似药，因此未纳入接受 IFX 治疗的患者。在两项研究中均使用了严格的纳入标准，以避免出现不必要的变量；研究前无患者使用 TNFi，且 TNFi 仅与甲氨蝶呤联合使用。根据 EULAR 缓解标准定义临床缓解。在比较研究中，两种测定方法表现相当。因此，由于其在临床环境中的可行性，选择 ELISA 进行前瞻性研究。横断面研究发现，仅在接受 IFX 和 ADL 治疗的组中发现 ADAb，这与血液中药物药理作用的降低有关。前瞻性研究中也发现了接受 ADL 治疗的组有类似的结果，该研究还表明药物/ADAb 水平与临床缓解丧失之间存在关联。总之，我们的研究结果支持在真实临床环境中进行药物和抗药物 Ab 监测，从而实现个体化治疗并减少慢性炎症性关节炎的残疾。
