Abstract:
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn\'s disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual\'s drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.
摘要:
炎症性肠病(IBD)是一种以腹泻为特征的消化道慢性炎症性疾病,直肠出血,和腹痛。IBD主要包括克罗恩病和溃疡性结肠炎。IBD是一种使人衰弱的疾病,可导致危及生命的并发症,涉及可能的恶性肿瘤和手术。可用的疗法旨在实现长期缓解并防止疾病进展。生物制品是主要靶向蛋白质的生物工程治疗药物。尽管他们彻底改变了IBD的治疗方法,它们的潜在治疗益处是有限的,因为在疗效和毒性方面的临床反应存在巨大的个体差异,导致长期治疗失败率高。因此,重要的是找到提供允许患者分层以最大化治疗益处和最小化不良事件的定制治疗策略的生物标志物。药物遗传学有可能通过识别遗传变异来优化IBD中的生物制剂选择,特别是单核苷酸多态性(SNP),这些是与个体药物反应相关的潜在因素。这篇综述分析了与生物制剂反应相关的遗传变异的当前知识(英夫利昔单抗,阿达木单抗,ustekinumab,和维多珠单抗)在IBD中。在各种数据库中进行了在线文献检索。在应用纳入和排除标准后,1685年结果中的28份报告被用于审查。可能用作治疗反应预测生物标志物的最重要的SNP与免疫有关,细胞因子产生,和免疫识别。