Durak Ediboğlu Elif, Çınar Muhammed, Kozacı Didem, Solmaz Dilek, Sargın Gökhan, Karadağ Ömer, Kınıklı Gülay, Kalyoncu Umut, Yılmaz Sedat, Şentürk Taşkın, Kabadayı Gökhan, Keser Gökhan, Hatemi Gülen, Kaya Kübra, Özmen Mustafa, Yargucu Figen, Özgüler Yeşim, Cefle Ayşe, Gerçik Önay, Kısacık Bünyamin, Akar Servet
Division of Rheumatology, Department of Internal Medicine, Izmir Katip Celebi University Faculty of Medicine, Izmir, Türkiye.
Division of Rheumatology, Department of Internal Medicine, University of Health Sciences, Gulhane Faculty of Medicine, Ankara, Türkiye.
Eur J Rheumatol. 2024 Oct 14;11(3):364-370. doi: 10.5152/eurjrheum.2024.24013.
To evaluate the development of anti-drug antibodies (ADAb) against tumor necrosis factor inhibitors (TNFi) therapy during a 2-year period and search the factors linked to patients with axial spondyloarthritis (axSpA).
Biologic-naive patients with axSpA were included in this observational study. Serum drug levels and ADAb were measured at weeks 12, 24, 52, and 104 of treatment by enzyme-linked immunosorbent assay (ELISA). The development of ADAb and factors related to ADAb over time were investigated using generalized estimating equations (GEE).
A total of 180 patients with axSpA (116 male, mean (±SD) 45.6 (±11.9) years) who started TNFi treatment (etanercept (32.2%), adalimumab (27.2%), golimumab (20.6%), infliximab (20%)) were included. In the etanercept treatment group, only 1 patient had ADAb at 12 weeks and 24 weeks. Anti-drug antibodies against TNFi drugs were present in the adalimumab group in 32.7% of patients and in the infliximab group in 21.2% of patients at 12 weeks, and the proportion of ADAb-positive patients were found to be stable throughout the follow-up for adalimumab- and infliximab-treated patients. In the golimumab group, one patient had ADAb against golimumab at 12 weeks and the proportion of ADAb-positive patients increased throughout follow-up. In longitudinal analysis, baseline age, TNFi type, longitudinal Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASDAS-CRP scores, serum C-eeactive protein (CRP) levels, presence of adverse events and treatment discontinuation were associated with the presence of ADAb.
The development of ADAb against TNFi therapy is associated with younger age, high disease activity, the development of adverse events and more common treatment discontinuation in patients with axSpA during 2-year follow-up.
评估在2年期间抗药物抗体（ADAb）针对肿瘤坏死因子抑制剂（TNFi）治疗的产生情况，并探寻与轴性脊柱关节炎（axSpA）患者相关的因素。
本观察性研究纳入了初治的axSpA患者。在治疗的第12、24、52和104周，通过酶联免疫吸附测定（ELISA）测量血清药物水平和ADAb。使用广义估计方程（GEE）研究ADAb的产生情况以及随时间与ADAb相关的因素。
共纳入180例开始TNFi治疗（依那西普（32.2%）、阿达木单抗（27.2%）、戈利木单抗（20.6%）、英夫利昔单抗（20%））的axSpA患者（116例男性，平均（±标准差）45.6（±11.9）岁）。在依那西普治疗组中，仅1例患者在12周和24周时有ADAb。在12周时，阿达木单抗组32.7%的患者以及英夫利昔单抗组21.2%的患者存在针对TNFi药物的抗药物抗体，并且发现阿达木单抗和英夫利昔单抗治疗患者在整个随访期间ADAb阳性患者的比例保持稳定。在戈利木单抗组中，1例患者在12周时有针对戈利木单抗的ADAb，并且ADAb阳性患者的比例在整个随访期间增加。在纵向分析中，基线年龄、TNFi类型、纵向巴斯强直性脊柱炎疾病活动指数（BASDAI）和ASDAS-CRP评分、血清C反应蛋白（CRP）水平、不良事件的发生以及治疗中断与ADAb的存在相关。
在2年随访期间，axSpA患者中针对TNFi治疗产生ADAb与年龄较小、疾病活动度高、不良事件的发生以及更常见的治疗中断相关。
