Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Unit of Immunoallergology, Careggi University Hospital, Florence, Italy.
J Allergy Clin Immunol Pract. 2018 Nov-Dec;6(6):2065-2072.e2. doi: 10.1016/j.jaip.2018.04.007. Epub 2018 Apr 13.
Hypersensitivity reactions (HRs) and loss of response (LOR) to infliximab (IFX) are related to drug immunogenicity characterized by antidrug antibodies (ADAs).
To analyze the timing of ADA appearance and its relationship with drug levels and clinical outcomes in IFX-treated patients with different diseases.
Samples were longitudinally collected before each infusion from 91 IFX-treated patients and were assayed for ADA and drug levels by enzyme-linked immunosorbent assay and for IgE by ImmunoCAP system. Clinical data regarding efficacy and safety of therapy were also monitored.
The ADA onset occured quite early, irrespective of the type of disease, during the first year and more frequently and earlier during the second cycle of therapy. Patients with HR were more frequently ADA-positive and with higher ADA titers compared with other patient groups. ADA onset tends to precede HRs and LOR; all HRs that occur after a period of drug interruption are preceded by ADA development. Before ADA detection, a progressive decline in IFX levels until a complete disappearance was observed. The ADA titer was maintained for years both in patients with ongoing therapy and in those who interrupted it. IgE ADAs are more frequently developed in patients with higher ADA levels and earlier ADA onset, but their rate of negativization is faster.
The present data suggest that most IFX-exposed patients develop ADAs within the first year of treatment irrespective of disease type. The clinical outcome to the treatment is preceded by ADA development, which in turn is associated with the reduction in drug serum levels. Both ADA evaluation and therapeutic drug monitoring may have a relevant impact on clinical practice, giving new insights to predict LOR and HRs.
对英夫利昔单抗（IFX）的过敏反应（HR）和应答丧失（LOR）与以抗药物抗体（ADA）为特征的药物免疫原性有关。
分析 ADA 出现的时间及其与不同疾病的 IFX 治疗患者的药物水平和临床结果的关系。
从 91 名接受 IFX 治疗的患者中，在每次输注前进行了纵向采样，并通过酶联免疫吸附测定法测定 ADA 和药物水平，通过免疫捕获系统测定 IgE。还监测了与治疗疗效和安全性相关的临床数据。
ADA 的出现相当早，与疾病类型无关，在第一年期间以及在治疗的第二个周期中更频繁且更早。与其他患者组相比，出现 HR 的患者更常为 ADA 阳性且 ADA 滴度更高。ADA 的出现往往先于 HR 和 LOR；在药物中断后发生的所有 HR 均先于 ADA 的发展。在 ADA 检测之前，观察到 IFX 水平逐渐下降，直到完全消失。ADA 滴度在接受持续治疗和中断治疗的患者中均保持多年。在具有持续治疗的患者和中断治疗的患者中，ADA 滴度都保持了多年。在具有更高 ADA 水平和更早 ADA 发病的患者中，IgE ADA 更常被发现，但它们的阴性化速度更快。
目前的数据表明，无论疾病类型如何，大多数接受 IFX 治疗的患者在治疗的第一年都会产生 ADA。治疗的临床结果先于 ADA 的发展，而 ADA 的发展又与药物血清水平的降低有关。ADA 的评估和治疗药物监测都可能对临床实践产生重大影响，为预测 LOR 和 HR 提供新的见解。
