*Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; and†Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Inflamm Bowel Dis. 2017 Dec;23(12):2202-2208. doi: 10.1097/MIB.0000000000001255.
Vedolizumab (VDZ) has been approved for the treatment of patients with moderate-to-severe Crohn's disease and ulcerative colitis. The GEMINI trials reported a low prevalence of anti-VDZ antibodies (AVA). However, the AVA assays used in GEMINI were drug sensitive, resulting in a possible underestimation of the rate of AVA formation. This study aimed to monitor immunogenicity of VDZ in a real-life cohort using a drug-resistant AVA assay.
Using a combination of VDZ/AVA complex precipitation and acid dissociation, a drug-resistant assay for AVA detection in the presence of high VDZ concentrations has been developed and analytically validated. The assay was applied on serum samples of 179 VDZ-treated patients with inflammatory bowel disease to evaluate the prevalence and time course of AVA.
A dose-response curve ranging from 25 to 1600 ng/mL using 1/125 diluted serum was obtained, allowing the detection of AVA concentrations up to 200 μg/mL of MA-VDZ19C11 equivalents, a calibrator antibody to VDZ. This assay was highly AVA specific and drug resistant. Four of 179 VDZ-treated patients (2.2%) were AVA positive and AVA were detected already after the first VDZ infusion. AVA were all transient in these patients without need for any dosage optimization. There was no correlation between VDZ and AVA concentrations in the AVA-positive samples.
AVA appear from the first VDZ infusion onward and disappear over time. The low prevalence of AVA suggests that immunogenicity does not influence response to treatment.
维得利珠单抗（VDZ）已被批准用于治疗中重度克罗恩病和溃疡性结肠炎患者。GEMINI 试验报告了抗 VDZ 抗体（AVA）的低发生率。然而，GEMINI 中使用的 AVA 检测方法对药物敏感，这可能导致 AVA 形成率被低估。本研究旨在使用耐药性 AVA 检测方法在真实队列中监测 VDZ 的免疫原性。
使用 VDZ/AVA 复合物沉淀和酸解离相结合的方法，开发了一种在存在高 VDZ 浓度时用于检测 AVA 的耐药性检测方法，并对其进行了分析验证。该检测方法应用于 179 例接受 VDZ 治疗的炎症性肠病患者的血清样本中，以评估 AVA 的发生率和时间过程。
使用 1/125 稀释血清获得了 25 至 1600ng/mL 的剂量反应曲线，允许检测高达 200μg/mL 的 MA-VDZ19C11 等效物（VDZ 的校准抗体）的 AVA 浓度。该检测方法对 AVA 具有高度特异性和耐药性。在 179 例接受 VDZ 治疗的患者中，有 4 例（2.2%）AVA 阳性，并且在首次 VDZ 输注后即可检测到 AVA。在这些患者中，AVA 均为一过性，无需进行任何剂量优化。在 AVA 阳性样本中，VDZ 与 AVA 浓度之间没有相关性。
AVA 从第一次 VDZ 输注开始出现，并随时间消失。AVA 的低发生率表明免疫原性不会影响治疗反应。
