背景:针对生物制剂的抗药物抗体(ADAs)的形成是牛皮癣治疗失败的重要原因。
目的:本研究旨在总结银屑病患者在不同生物治疗下ADAs形成的特点以及ADAs对生物制剂临床疗效和安全性的影响。
方法:PubMed,Embase,从成立到2022年8月,搜索了WebofScience数据库。包括评估银屑病患者ADA水平的生物制剂研究。Cochrane偏倚风险工具用于评估随机对照试验(RCT)的质量,纽卡斯尔-渥太华质量评估量表(NOS)用于病例对照和队列研究,以及JoannaBriggs研究所(JBI)单臂研究的关键评估清单。我们使用R软件用随机效应模型计算了合并发生率。亚组分析显示,患者特征的差异,疾病状况,研究设计,和免疫测定可能会影响ADA的产生和检测。
结果:分析包括86项研究,总人口为42,280人。汇总的ADA率为0.49%,2.20%,2.38%,4.08%,7.38%,7.94%,14.29%,21.93%,29.70%,31.76%,苏金单抗占39.58%,依那西普,Brodalumab,ustekinumab,tildrakizumab,guselkumab,ixekizumab,risankizumab,英夫利昔单抗,阿达木单抗,还有bimekizumab,分别。>70%(95%CI,0.71-0.81)的针对阿达木单抗的ADAs是中和抗体,超过70%的针对苏金单抗和布罗达鲁单抗的ADAs是短暂的。甲氨蝶呤与肿瘤坏死因子-α(TNF-α)抑制剂同时治疗可降低ADA水平。较低的英夫利昔单抗剂量和使用白介素(IL)-23p19抑制剂的间歇性治疗增加了ADA的形成。此外,使用TNF-α抑制剂和IL-12/23p40抑制剂治疗的ADA形成与较低的反应率或血清药物水平相关,但只有高ADA滴度降低了IL-17抑制剂的临床效果。IL-23p19和TNF-α抑制剂的发生与注射部位反应有关。
结论:在11种生物制剂中,苏金单抗,依那西普,和brodalumab导致最低的ADA形成率。免疫原性导致较低的生物功效和较高的注射部位反应可能性。低剂量,间歇性治疗可能会增加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。
BACKGROUND: Formation of anti-drug antibodies (ADAs) against biologics is an important cause of psoriasis treatment failure.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.