Department of Paediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht.
Faculty of Medicine, Utrecht University.
Rheumatology (Oxford). 2019 Oct 1;58(10):1839-1849. doi: 10.1093/rheumatology/kez030.
The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the prevalence of ADAbs in JIA studies; investigate the effect of ADAbs on treatment efficacy and adverse events; and explore the effect of immunosuppressive therapy on antibody formation.
PubMed, Embase and the Cochrane Library were systematically searched to identify relevant clinical trials and observational studies that reported prevalence of ADAbs. Studies were systematically reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses and appropriate proportional and pairwise meta-analyses were performed.
A total of 5183 references were screened; 28 articles, involving 26 studies and 2354 JIA patients, met eligibility criteria. Prevalence of ADAbs ranged from 0% to 82% across nine biologic agents. Overall pooled prevalence of ADAbs was 16.9% (95% CI, 9.5, 25.9). Qualitative analysis of included studies indicated that antibodies to infliximab, adalimumab, anakinra and tocilizumab were associated with treatment failure and/or hypersensitivity reactions. Concomitant MTX uniformly reduced the risk of antibody formation during adalimumab treatment (risk ratio 0.33; 95% CI 0.21, 0.52).
The association of ADAbs with treatment failure and hypersensitivity reactions indicates their clinical relevance in paediatric patients with JIA. Based on our findings, we recommend a preliminary course of action regarding immunogenicity of biologic agents in patients with JIA. Further strategies to predict, prevent, detect and manage immunogenicity could optimize treatment outcomes and personalize treatment with biologic therapies.
抗药物抗体（ADAbs）在儿科幼年特发性关节炎（JIA）患者中的临床影响尚不清楚。本系统评价和荟萃分析旨在总结 JIA 研究中 ADAbs 的患病率；探讨 ADAbs 对治疗效果和不良事件的影响；并探讨免疫抑制治疗对抗体形成的影响。
系统检索 PubMed、Embase 和 Cochrane 图书馆，以确定报告 ADAbs 患病率的相关临床试验和观察性研究。根据系统评价和荟萃分析的首选报告项目进行系统综述，并进行适当的比例和成对荟萃分析。
共筛选出 5183 篇参考文献；28 篇文章，涉及 26 项研究和 2354 例 JIA 患者，符合入选标准。9 种生物制剂的 ADAbs 患病率从 0%到 82%不等。总体 ADAbs 患病率为 16.9%（95%CI，9.5%，25.9%）。纳入研究的定性分析表明，针对英夫利昔单抗、阿达木单抗、阿那白滞素和托珠单抗的抗体与治疗失败和/或过敏反应有关。同时使用 MTX 可均匀降低阿达木单抗治疗时抗体形成的风险（风险比 0.33；95%CI 0.21，0.52）。
ADAbs 与治疗失败和过敏反应相关表明其在儿科 JIA 患者中的临床相关性。基于我们的发现，我们建议针对 JIA 患者生物制剂的免疫原性采取初步行动。进一步预测、预防、检测和管理免疫原性的策略可以优化治疗效果并实现生物治疗的个体化。
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