Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
University of California Riverside School of Medicine, Riverside, CA, USA.
J Dermatolog Treat. 2022 Dec;33(8):3080-3085. doi: 10.1080/09546634.2022.2114288. Epub 2022 Aug 31.
Biologics may elicit the production of anti-drug antibodies (ADAs), the clinical significance of which is not fully understood. ADA development in psoriasis patients on IL-17 inhibitors was evaluated by incidence, impact on efficacy, and relationship with adverse events. We systematically searched PubMed, Cochrane, and Embase databases, identifying 456 references. Seventeen studies met inclusion criteria. ADA incidence was: 0% to 5.5% (secukinumab), 11% to 19.4% (ixekizumab), 0% to 3.3% (brodalumab), and 19% to 39% (bimekizumab). Neutralizing antibody incidence was: 0% to 1.5% (secukinumab), 0% to 3.5% (ixekizumab), and 0% (brodalumab). ADA presence alone with secukinumab, ixekizumab, and bimekizumab did not impact drug efficacy. Brodalumab was the only one of the IL-17 inhibitors, which showed a reduction in efficacy in ADA + patients. In one analysis, high ADA titers to ixekizumab were associated with diminished treatment response. ADAs to secukinumab and bimekizumab were not associated with adverse events. There were limited data on ADAs and safety with ixekizumab or brodalumab. Overall, when monitoring patients on secukinumab, ADAs, titers, and the presence of neutralizing antibodies were not prognostic of outcomes. However, monitoring for ADAs with brodalumab and measuring titers with ixekizumab may be of value clinically.
生物制剂可能会引起抗药物抗体(ADA)的产生,但其临床意义尚未完全了解。通过发生率、对疗效的影响以及与不良反应的关系,评估了白细胞介素-17 抑制剂治疗银屑病患者的 ADA 发展情况。我们系统地检索了 PubMed、Cochrane 和 Embase 数据库,共识别出 456 篇参考文献。有 17 项研究符合纳入标准。ADA 的发生率为:0%至 5.5%(司库奇尤单抗)、11%至 19.4%(依奇珠单抗)、0%至 3.3%(布罗达单抗)和 19%至 39%(倍美莫司单抗)。中和抗体的发生率为:0%至 1.5%(司库奇尤单抗)、0%至 3.5%(依奇珠单抗)和 0%(布罗达单抗)。仅在司库奇尤单抗、依奇珠单抗和倍美莫司单抗中,ADA 阳性患者的药物疗效不受影响。布罗达单抗是唯一一种白细胞介素-17 抑制剂,其在 ADA+患者中的疗效降低。在一项分析中,高滴度的抗依奇珠单抗抗体与治疗反应减弱相关。抗司库奇尤单抗和倍美莫司单抗的抗体与不良反应无关。关于依奇珠单抗或布罗达单抗的 ADA 和安全性数据有限。总体而言,在监测司库奇尤单抗治疗的患者时,ADA、抗体滴度和中和抗体的存在并不能预测结局。然而,监测布罗达单抗的 ADA 并测量依奇珠单抗的抗体滴度可能具有临床价值。