Chen Howard C, Shunyakova Jenny, Reddy Amit K, Pandiri Srujay, Hassman Lynn
John F. Hardesty Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States.
Department of Ophthalmology, University of Kansas City School of Medicine, Kansas City, MO, United States.
Front Ophthalmol (Lausanne). 2025 Jan 28;5:1432935. doi: 10.3389/fopht.2025.1432935. eCollection 2025.
Adalimumab taken every other week is an effective treatment in patients with chronic refractory uveitis. Patients who have a suboptimal response to this treatment may suffer from recurrent inflammation and vision loss. Here, we investigated the use of therapeutic drug monitoring and neutralizing anti-drug antibody detection as a strategy to optimize tumor necrosis factor (TNF)-alpha inhibitor treatment in patients who have a suboptimal response to the initial dosing of adalimumab.
Retrospective cohort study performed in two tertiary referral uveitis services in the United States between 2015 to 2023. Patients with non-infectious uveitis who had a suboptimal response to every two-week dosing of adalimumab and underwent serum adalimumab level with reflex to anti-drug antibody testing were followed. Patients were considered to have neutralizing drug antibodies when serum drug levels were low (less than or equal to 6 mcg/mL) and anti-adalimumab antibodies were present on reflex testing. Treatment adjustment was made by clinicians with the knowledge of serum adalimumab level and the presence or absence of neutralizing drug antibodies. Every two-week dosing of adalimumab was either escalated to weekly dosing or switched to infliximab, an alternate TNF-alpha inhibitor, based on these findings. The primary outcome was success or failure at 12 months, as determined by disease inactivity on steroid-sparing therapy.
32 patients with suboptimal response to the initial dosing of adalimumab were included. 31.2% (n=10) of patients were found to have neutralizing drug antibodies. All patients with neutralizing drug antibodies underwent a medication switch to infliximab with a remission rate of 40% at 12 months. Patients without neutralizing drug antibodies (n=22) underwent dose escalation (77.3%; n=17) or medication switch (22.7%; n=5) and achieved a remission rate of 68.2% at 12 months. Altogether, treatment adjustment based on therapeutic drug monitoring and neutralizing drug antibody detection, in our cohort, resulted in a remission rate of 62.5%.
For patients with uveitis experiencing suboptimal therapeutic response to adalimumab dosed every two weeks, therapeutic drug monitoring and neutralizing drug antibody detection may help clinicians optimize TNF-alpha inhibitor treatment.
每隔一周注射一次阿达木单抗是治疗慢性难治性葡萄膜炎患者的有效方法。对这种治疗反应欠佳的患者可能会反复出现炎症并导致视力丧失。在此，我们研究了使用治疗药物监测和中和性抗药物抗体检测作为一种策略，以优化对初始剂量阿达木单抗反应欠佳的患者的肿瘤坏死因子（TNF）-α抑制剂治疗。
2015年至2023年期间在美国两家三级转诊葡萄膜炎治疗中心进行的回顾性队列研究。对每两周注射一次阿达木单抗反应欠佳且进行了血清阿达木单抗水平检测及抗药物抗体检测的非感染性葡萄膜炎患者进行随访。当血清药物水平较低（小于或等于6微克/毫升）且在进一步检测中存在抗阿达木单抗抗体时，患者被认为存在中和性药物抗体。临床医生根据血清阿达木单抗水平以及是否存在中和性药物抗体进行治疗调整。根据这些结果，每两周一次的阿达木单抗给药方案要么增加至每周一次，要么换用另一种TNF-α抑制剂英夫利昔单抗。主要结局是12个月时的成功或失败，通过停用类固醇治疗时的疾病非活动状态来确定。
纳入了32例对初始剂量阿达木单抗反应欠佳的患者。31.2%（n = 10）的患者被发现存在中和性药物抗体。所有存在中和性药物抗体的患者均换用了英夫利昔单抗，12个月时的缓解率为40%。不存在中和性药物抗体的患者（n = 22）进行了剂量增加（77.3%；n = 17）或药物更换（22.7%；n = 5），12个月时的缓解率为68.2%。总体而言，在我们的队列中，基于治疗药物监测和中和性药物抗体检测进行治疗调整后，缓解率为62.5%。
对于每两周注射一次阿达木单抗治疗反应欠佳的葡萄膜炎患者，治疗药物监测和中和性药物抗体检测可能有助于临床医生优化TNF-α抑制剂治疗。
