China Novartis Institutes for Bio-medical Research CO., Shanghai, China.
Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Department of Statistics, University of Oxford, Oxford, UK.
Am J Hum Genet. 2023 Oct 5;110(10):1817-1824. doi: 10.1016/j.ajhg.2023.08.010. Epub 2023 Sep 1.
Response to the anti-IL17 monoclonal antibody secukinumab is heterogeneous, and not all participants respond to treatment. Understanding whether this heterogeneity is driven by genetic variation is a key aim of pharmacogenetics and could influence precision medicine approaches in inflammatory diseases. Using changes in disease activity scores across 5,218 genotyped individuals from 19 clinical trials across four indications (psoriatic arthritis, psoriasis, ankylosing spondylitis, and rheumatoid arthritis), we tested whether genetics predicted response to secukinumab. We did not find any evidence of association between treatment response and common variants, imputed HLA alleles, polygenic risk scores of disease susceptibility, or cross-disease components of shared genetic risk. This suggests that anti-IL17 therapy is equally effective regardless of an individual's genetic background, a finding that has important implications for future genetic studies of biological therapy response in inflammatory diseases.
对抗白介素 17 单克隆抗体司库奇尤单抗的反应存在异质性，并非所有参与者对治疗都有反应。了解这种异质性是否由遗传变异驱动是药物遗传学的主要目标，并且可能会影响炎症性疾病的精准医疗方法。我们利用来自四个适应症（银屑病关节炎、银屑病、强直性脊柱炎和类风湿关节炎）的 19 项临床试验中 5218 名基因分型个体的疾病活动评分变化，检测了遗传因素是否可以预测司库奇尤单抗的反应。我们没有发现治疗反应与常见变异、推断的 HLA 等位基因、疾病易感性的多基因风险评分或共享遗传风险的跨疾病成分之间存在任何关联的证据。这表明抗白介素 17 治疗的效果是相同的，无论个体的遗传背景如何，这一发现对未来炎症性疾病生物治疗反应的遗传研究具有重要意义。
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