Lim Sung Ho, Kim Khangyoo, Choi Chang-Ik
Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea.
College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea.
J Pers Med. 2022 Jul 31;12(8):1265. doi: 10.3390/jpm12081265.
Precision medicine refers to a highly individualized and personalized approach to patient care. Pharmacogenomics is the study of how an individual's genomic profile affects their drug response, enabling stable and effective drug selection, minimizing side effects, and maximizing therapeutic efficacy. Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in the joints. It mainly starts in peripheral joints, such as the hands and feet, and progresses to large joints, which causes joint deformation and bone damage due to inflammation of the synovial membrane. Here, we review various pharmacogenetic studies investigating the association between clinical response to monoclonal antibody therapy and their target genetic polymorphisms. Numerous papers have reported that some single nucleotide polymorphisms (SNPs) are related to the therapeutic response of several monoclonal antibody drugs including adalimumab, infliximab, rituximab, and tocilizumab, which target tumor necrosis factor (TNF), CD20 of B-cells, and interleukin (IL)-6. Additionally, there are some pharmacogenomic studies reporting on the association between the clinical response of monoclonal antibodies having various mechanisms, such as IL-1, IL-17, IL-23, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the receptor activator of nuclear factor-kappa B (RANK) inhibition. Biological therapies are currently prescribed on a "trial and error" basis for RA patients. If appropriate drug treatment is not started early, joints may deform, and long-term treatment outcomes may worsen. Pharmacogenomic approaches that predict therapeutic responses for RA patients have the potential to significantly improve patient quality of life and reduce treatment costs.
精准医学是指针对患者护理采取的高度个体化和个性化的方法。药物基因组学研究个体的基因组特征如何影响其药物反应,从而实现稳定有效的药物选择,将副作用降至最低,并使治疗效果最大化。类风湿性关节炎(RA)是一种自身免疫性疾病,会导致关节慢性炎症。它主要始于外周关节,如手和脚,然后发展到大型关节,由于滑膜炎症导致关节变形和骨质破坏。在此,我们综述了各种药物遗传学研究,这些研究调查了单克隆抗体治疗的临床反应与其目标基因多态性之间的关联。许多论文报道,一些单核苷酸多态性(SNP)与包括阿达木单抗、英夫利昔单抗、利妥昔单抗和托珠单抗在内的几种单克隆抗体药物的治疗反应有关,这些药物分别靶向肿瘤坏死因子(TNF)、B细胞的CD20和白细胞介素(IL)-6。此外,还有一些药物基因组学研究报道了具有各种作用机制的单克隆抗体的临床反应之间的关联,如IL-1、IL-17、IL-23、粒细胞-巨噬细胞集落刺激因子(GM-CSF)以及核因子-κB受体激活剂(RANK)抑制。目前,RA患者的生物疗法是在“试错”的基础上开处方的。如果不及早开始适当的药物治疗,关节可能会变形,长期治疗效果可能会恶化。预测RA患者治疗反应的药物基因组学方法有可能显著提高患者的生活质量并降低治疗成本。