Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
J Intern Med. 2022 Sep;292(3):477-491. doi: 10.1111/joim.13495. Epub 2022 Apr 26.
Anti-drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events.
To identify risk factors for ADAb in the early phase of infliximab treatment.
Patients (n = 410) with immune-mediated inflammatory diseases who initiated infliximab treatment were included in the 38-week Norwegian Drug Monitoring Trial (NOR-DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders.
ADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0-3.6]) and lifetime smoking (OR, 2.0 [CI 1.1-3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2-0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2-0.8]) reduced the risk of ADAb. Higher disease activity during follow-up (OR, 1.1 [CI 1.0-1.1]) and "drug holidays" of more than 11 weeks (OR, 4.1 [CI 1.2-13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0-0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6-0.8]) reduced the risk of immunogenicity.
Several risk factors for ADAb formation during early-phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance.
抗药物抗体 (ADAb) 在英夫利昔单抗和其他肿瘤坏死因子 (TNF) 抑制剂的治疗早期经常形成，导致治疗失败和不良事件。
确定英夫利昔单抗治疗早期 ADAb 的风险因素。
本研究纳入了 410 名开始英夫利昔单抗治疗的免疫介导性炎症性疾病患者，他们被纳入了为期 38 周的挪威药物监测试验 (NOR-DRUM) A，并按 1:1 随机分配至治疗药物监测 (TDM) 或标准治疗。在每次输注时测量英夫利昔单抗和 ADAb 的血清水平。使用逻辑回归评估 ADAb 形成的可能风险因素，并针对潜在混杂因素进行调整。
78 名 (19%) 患者检测到 ADAb。类风湿关节炎 (RA) 的诊断 (比值比 [OR]，1.9 [95%置信区间 [CI] 1.0-3.6]) 和终生吸烟 (OR，2.0 [CI 1.1-3.6]) 是基线风险因素，而基线时使用伴随免疫抑制剂 (OR，0.4 [CI 0.2-0.8]) 和诊断为脊柱关节炎 (SpA) (OR，0.4 [CI 0.2-0.8]) 降低了 ADAb 的风险。随访期间更高的疾病活动度 (OR，1.1 [CI 1.0-1.1]) 和超过 11 周的“药物假期” (OR，4.1 [CI 1.2-13.8]) 增加了 ADAb 的风险，而更高的英夫利昔单抗剂量 (OR，0.1 [CI 0.0-0.3) 和更高的血清英夫利昔单抗浓度 (OR，0.7 [CI 0.6-0.8]) 降低了免疫原性的风险。
确定了英夫利昔单抗治疗早期 ADAb 形成的几个风险因素。这些知识为治疗策略提供了依据，以减轻 ADAb 的形成，并确定这些措施特别重要的患者。
