Zur Bonsen Lynn S, Knecht Vitus A, Rübsam Anne, Pohlmann Dominika, Pleyer Uwe
Department of Ophthalmology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Biomedicines. 2024 Dec 6;12(12):2782. doi: 10.3390/biomedicines12122782.
Adalimumab, an anti-TNF-α biologic agent, has emerged as a principal treatment option for patients with non-infectious uveitis. The influence of adalimumab anti-drug antibodies (AAA) on the efficacy of adalimumab therapy is not yet fully understood. We aim to understand their clinical implications in the context of therapeutic drug monitoring and the factors contributing to the formation of these antibodies.
We conducted a retrospective analysis of 114 patients with non-infectious uveitis who developed AAA while undergoing adalimumab therapy.
Among the 114 AAA-positive uveitis patients, a significant correlation was observed between AAA levels and reduced adalimumab serum levels (r = -0.58, < 0.001). The mean time to AAA detection was 2.1 years (range 0.1-11.9 years), with 45.6% of cases identified through routine testing. If AAA levels were initially low, subsequent measurements for AAA were more likely to become negative during treatment (r = 0.63, < 0.001). Higher AAA concentrations were associated with a shorter time to detection (r = -0.27, = 0.01) and younger age (r = -0.21, = 0.03). There was a trend, though no significant influence, of concomitant immunosuppression with prednisolone ≤ 7.5 mg or methotrexate on antibody formation ( = 0.18). No significant difference was observed in AAA levels between uveitis subtypes.
Higher AAA concentrations are associated with lower adalimumab serum levels in uveitis patients. Routine clinical testing is essential for optimal therapeutic drug monitoring to prevent early loss of effectiveness.
阿达木单抗是一种抗TNF-α生物制剂，已成为非感染性葡萄膜炎患者的主要治疗选择。阿达木单抗抗药抗体（AAA）对阿达木单抗治疗效果的影响尚未完全明确。我们旨在了解其在治疗药物监测背景下的临床意义以及这些抗体形成的影响因素。
我们对114例在接受阿达木单抗治疗时出现AAA的非感染性葡萄膜炎患者进行了回顾性分析。
在114例AAA阳性的葡萄膜炎患者中，观察到AAA水平与阿达木单抗血清水平降低之间存在显著相关性（r = -0.58，P < 0.001）。检测到AAA的平均时间为2.1年（范围0.1 - 11.9年），45.6%的病例通过常规检测发现。如果AAA水平最初较低，治疗期间后续的AAA检测更有可能转为阴性（r = 0.63，P < 0.001）。较高的AAA浓度与检测时间较短（r = -0.27，P = 0.01）和年龄较小（r = -0.21，P = 0.03）相关。泼尼松龙≤7.5 mg或甲氨蝶呤联合免疫抑制对抗体形成有趋势性影响，但无显著影响（P = 0.18）。葡萄膜炎亚型之间的AAA水平未观察到显著差异。
葡萄膜炎患者中较高的AAA浓度与较低的阿达木单抗血清水平相关。常规临床检测对于优化治疗药物监测以防止早期疗效丧失至关重要。
