From the Eye Institute, Cleveland Clinic Abu Dhabi (F.P., S.D.S., S.H.A., P.N.), Abu Dhabi, United Arab Emirates.; Cleveland Clinic Lerner College of Medicine (F.P., S.D.S., P.N.), Case Western Reserve University, Cleveland, Ohio, USA.
From the Eye Institute, Cleveland Clinic Abu Dhabi (F.P., S.D.S., S.H.A., P.N.), Abu Dhabi, United Arab Emirates.; Cleveland Clinic Lerner College of Medicine (F.P., S.D.S., P.N.), Case Western Reserve University, Cleveland, Ohio, USA.
Am J Ophthalmol. 2024 Dec;268:306-311. doi: 10.1016/j.ajo.2024.09.008. Epub 2024 Sep 11.
To explore the incidence of antibodies against adalimumab (AAA) development in noninfectious uveitis (NIU) and to examine the impact of treatment adjustment in nonresponders.
Retrospective case series.
In this single-center study of patients with NIU treated with adalimumab, blood samples for adalimumab and AAA were collected and therapeutic adjustments post-monitoring in non-responders were analyzed including changes in injection intervals, addition of conventional disease-modifying antirheumatic drugs (cDMARD), and treatment alterations to biologic DMARD. The main outcome measures were the proportion of patients with positive AAA and active uveitis, decrease of AAA at final follow-up by different therapeutic interventions.
Of 42 patients who underwent laboratory investigations at 17.9 months after adalimumab initiation, 22 (52.4%) patients who were nonresponders demonstrated AAA (1243 ng/mL) with a mean adalimumab trough level of 3.0 µg/mL, significantly lower than the mean drug levels of patients without AAA (11.8 µg/mL). Fifteen (35.7%) patients were receiving concurrent treatment with a second immunosuppressive agent, but the mean antibody level and the mean adalimumab level were not statistically significantly different from the monotherapy group (P = .13 and P = .34). Reduction in AAA levels and relapse management was greatest among nonresponders who were treated by increasing the adalimumab dose and adding an additional immunosuppressive drug (-3565 ng/mL), followed by patients who were shifted to a different biologic (-1153 ug/mL).
The presence of AAA was detected in 88% of nonresponder patients and was associated with undetectable adalimumab drug levels. This underscores immunogenicity as a major cause of loss of response in uveitis patients receiving biotherapies. Increasing the dose of adalimumab injections together with the addition of low-dose cDMARDs was the most effective adjustment in immunized nonresponders for whom the adalimumab drug concentration was low.
探讨阿达木单抗（AAA）在非感染性葡萄膜炎（NIU）中的抗体产生情况，并研究治疗调整对无应答者的影响。
回顾性病例系列研究。
本研究纳入在单中心接受阿达木单抗治疗的 NIU 患者，采集血液样本检测阿达木单抗和 AAA，并分析无应答者的监测后治疗调整，包括注射间隔改变、添加常规疾病修饰抗风湿药物（cDMARD），以及生物 DMARD 治疗改变。主要观察指标是 AAA 阳性和活动性葡萄膜炎患者的比例，以及不同治疗干预措施最终随访时 AAA 减少情况。
在阿达木单抗治疗开始后 17.9 个月进行实验室检查的 42 例患者中，22 例（52.4%）无应答者出现 AAA（1243ng/ml），阿达木单抗谷浓度为 3.0μg/ml，显著低于无 AAA 患者（11.8μg/ml）。15 例（35.7%）患者同时接受第二种免疫抑制剂治疗，但抗体水平和阿达木单抗水平与单药组无统计学差异（P=0.13 和 P=0.34）。增加阿达木单抗剂量并添加额外免疫抑制剂的无应答者 AAA 水平降低和复发管理效果最大（-3565ng/ml），其次是转换为另一种生物制剂的患者（-1153ug/ml）。
无应答患者中 88%存在 AAA，与阿达木单抗药物水平无法检测有关。这突显了免疫原性是接受生物治疗的葡萄膜炎患者失去应答的主要原因。对于免疫应答的无应答者，增加阿达木单抗注射剂量并添加低剂量 cDMARD 是最有效的调整方法，因为这些患者的阿达木单抗药物浓度较低。
