Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China.
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Department of Dermatology and Venereology, Peking University First Hospital, Beijing 100034, China.
Autoimmun Rev. 2024 Apr;23(4):103530. doi: 10.1016/j.autrev.2024.103530. Epub 2024 Mar 17.
Formation of anti-drug antibodies (ADAs) against biologics is an important cause of psoriasis treatment failure.
This study aimed to summarize the characteristics of ADAs formation under different biological therapies and the influence of ADAs on the clinical effects and safety of biologics in patients with psoriasis.
PubMed, Embase, and Web of Science databases were searched from their inception to August 2022. Studies on biologics that assessed ADA levels in patients with psoriasis were included. The Cochrane risk-of-bias tool was used to assess the quality of randomized controlled trials (RCTs), the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control and cohort studies, and the Joanna Briggs Institute (JBI) critical appraisal checklist for single-arm studies. We calculated the pooled incidence with a random-effects model using R software. Subgroup analyses revealed that differences in patient characteristics, disease conditions, study design, and immunoassays may influence ADA generation and detection.
The analysis included 86 studies, with a total population of 42,280 individuals. The pooled ADA rates were 0.49%, 2.20%, 2.38%, 4.08%, 7.38%, 7.94%, 14.29%, 21.93%, 29.70%, 31.76%, and 39.58% for secukinumab, etanercept, brodalumab, ustekinumab, tildrakizumab, guselkumab, ixekizumab, risankizumab, infliximab, adalimumab, and bimekizumab, respectively. >70% (95% CI, 0.71-0.81) of ADAs against adalimumab were neutralizing antibodies, and over 70% of ADAs against secukinumab and brodalumab were transient. Concomitant methotrexate therapy with tumor necrosis factor-α (TNF-α) inhibitors decreased ADA levels. Lower infliximab doses and intermittent therapy with interleukin (IL)-23 p19 inhibitors increased ADA formation. Additionally, ADA formation under treatment using TNF-α inhibitors and IL-12/23 p40 inhibitors was associated with lower response rates or serum drug levels, but only high ADA titers reduced the clinical effects of IL-17 inhibitors. The occurrence of IL-23 p19 and TNF-α inhibitors has been linked to injection-site reactions.
Among the 11 biologics, secukinumab, etanercept, and brodalumab resulted in the lowest ADA formation rates. Immunogenicity contributes to lower biological efficacy and a higher likelihood of injection-site reactions. Low doses, intermittent treatment may increase ADA formation. An appropriate biologic should be selected based on the ADA formation rate and course of treatment.
针对生物制剂的抗药物抗体（ADA）的形成是导致银屑病治疗失败的一个重要原因。
本研究旨在总结不同生物疗法下 ADA 形成的特点，以及 ADA 对银屑病患者生物制剂临床疗效和安全性的影响。
检索 PubMed、Embase 和 Web of Science 数据库，从建库至 2022 年 8 月，纳入评估银屑病患者 ADA 水平的生物制剂研究。采用 Cochrane 偏倚风险工具评估随机对照试验（RCT）的质量，纽卡斯尔-渥太华质量评估量表（NOS）评估病例对照和队列研究，Joanna Briggs 研究所（JBI）评价单臂研究的核对清单。使用 R 软件的随机效应模型计算汇总发生率。亚组分析揭示了患者特征、疾病状况、研究设计和免疫测定等方面的差异可能影响 ADA 的产生和检测。
纳入 86 项研究，共计 42280 人。分析显示，secukinumab、etanercept、brodalumab、ustekinumab、tildrakizumab、guselkumab、ixekizumab、risankizumab、infliximab、adalimumab 和 bimekizumab 的 ADA 发生率分别为 0.49%、2.20%、2.38%、4.08%、7.38%、7.94%、14.29%、21.93%、29.70%、31.76%和 39.58%。针对 adalimumab 的 ADA 中 >70%（95%CI：0.71-0.81）为中和抗体，secukinumab 和 brodalumab 的 ADA 大多为一过性。肿瘤坏死因子-α（TNF-α）抑制剂联合甲氨蝶呤治疗可降低 ADA 水平。较低的 infliximab 剂量和白细胞介素（IL）-23 p19 抑制剂间歇性治疗可增加 ADA 的形成。此外，TNF-α 抑制剂和 IL-12/23 p40 抑制剂治疗时 ADA 的形成与较低的应答率或血清药物水平相关，但只有高 ADA 滴度降低了 IL-17 抑制剂的临床疗效。IL-23 p19 和 TNF-α 抑制剂的发生与注射部位反应有关。
在这 11 种生物制剂中，secukinumab、etanercept 和 brodalumab 的 ADA 形成率最低。免疫原性导致生物制剂疗效降低和注射部位反应发生率升高。低剂量、间歇性治疗可能增加 ADA 的形成。应根据 ADA 形成率和治疗过程选择合适的生物制剂。
