Adalimumab is currently considered the most efficacious anti-TNFα agent for childhood noninfectious uveitis (NIU). The objective of this study was to define a therapeutic range for adalimumab trough levels in the treatment of childhood NIU. A retrospective, observational, pilot study of 36 children with NIU aged < 18 years, treated with adalimumab. Serum adalimumab through levels and adalimumab anti-drug antibodies (ADA) were analysed at least 24 weeks after start adalimumab. Adalimumab trough levels were significantly higher in complete responders 11.8 μg/mL (range 6.9–33.0) compared to partial or non-responders 9,2 μg/mL (range 0–13.6) (p = 0,004). Receiver–operator characteristics analyses with an area under the curve of 0,749 (95% CI, 0,561–0,937) defined 9.6 µg/mL as the lower margin for the therapeutic range. This cut-off corresponds with a sensitivity of 88% and a specificity of 56% (positive predictive value, 85%; negative predictive value, 62.5%). A concentration effect curve defined 13 µg/mL as the upper margin. Approximately one-third (30.5%) of patients had an adalimumab trough concentration exceeding 13 µg/mL. Free ADA were observed in 2 patients (5.5%). A therapeutic range of adalimumab trough levels of 9.6 to 13 µg/mL, which corresponds with an optimal clinical effect, was identified. Therapeutic drug monitoring may guide the optimisation of treatment efficacy in children with NIU in the treat-to-target era.

中文翻译：

---

确定小儿非感染性葡萄膜炎治疗中阿达木单抗血清浓度的治疗范围，迈向个性化治疗的一步

阿达木单抗目前被认为是治疗儿童非感染性葡萄膜炎（NIU）最有效的抗 TNFα 药物。本研究的目的是确定治疗儿童 NIU 时阿达木单抗谷水平的治疗范围。这是一项回顾性、观察性、试点研究，对象为 36 名年龄 < 18 岁的 NIU 儿童，接受阿达木单抗治疗。在开始使用阿达木单抗后至少 24 周对血清阿达木单抗水平和阿达木单抗抗药物抗体 (ADA) 进行分析。完全缓解者的阿达木单抗谷水平显着较高，为 11.8 μg/mL（范围 6.9-33.0），而部分或无缓解者为 9.2 μg/mL（范围 0-13.6）（p = 0,004）。接受者-操作者特征分析曲线下面积为 0,749 (95% CI, 0,561–0,937)，将 9.6 µg/mL 定义为治疗范围的下限。该截止值对应的敏感性为 88%，特异性为 56%（阳性预测值，85%；阴性预测值，62.5%）。浓度效应曲线将 13 µg/mL 定义为上限。大约三分之一 (30.5%) 的患者阿达木单抗谷浓度超过 13 µg/mL。2 名患者 (5.5%) 观察到游离 ADA。确定了阿达木单抗谷水平的治疗范围为 9.6 至 13 µg/mL，这与最佳临床效果相对应。治疗药物监测可以指导靶向治疗时代 NIU 儿童治疗效果的优化。