Jan Zainab, El Assadi Farah, Velayutham Dinesh, Mifsud Borbala, Jithesh Puthen Veettil
College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
Front Immunol. 2025 May 21;16:1521794. doi: 10.3389/fimmu.2025.1521794. eCollection 2025.
Tumor necrosis factor alpha inhibitors (TNFi) are biologic drugs that target TNFα, a key pro-inflammatory cytokine, to suppress disease activity and alleviate symptoms of various autoimmune diseases, including inflammatory bowel disease. This review focuses on the five US FDA-approved TNFi including the monoclonal antibodies Infliximab, Adalimumab, Golimumab, Certolizumab pegol and the soluble TNFα receptor fusion protein Etanercept, with a brief mention of other available biosimilars to TNFi. The review aims to summarize the recent evidence on the pharmacokinetics, pharmacodynamics, and pharmacogenomics of TNFi with a particular focus on Human Leukocyte Antigen (HLA) variants in terms of their genetic contribution to the response to TNFi. HLA variants have been linked to heterogeneity in the efficacy and safety of TNFi among patients. Building on the summarized evidence, the last part of the review discusses the potential clinical utility of testing for pharmacogenetic variants that are linked to the response to TNFi prior to the drug prescription, and it also addresses the future directions to achieve personalized treatment for TNFi users.
肿瘤坏死因子α抑制剂（TNFi）是一类生物药物，其作用靶点为关键促炎细胞因子肿瘤坏死因子α（TNFα），用于抑制疾病活动并缓解包括炎症性肠病在内的各种自身免疫性疾病的症状。本综述聚焦于美国食品药品监督管理局（FDA）批准的5种TNFi，包括单克隆抗体英夫利昔单抗、阿达木单抗、戈利木单抗、赛妥珠单抗聚乙二醇化制剂以及可溶性TNFα受体融合蛋白依那西普，并简要提及其他可用的TNFi生物类似药。本综述旨在总结TNFi在药代动力学、药效动力学和药物基因组学方面的最新证据，尤其关注人类白细胞抗原（HLA）变体对TNFi反应的遗传贡献。HLA变体与患者中TNFi疗效和安全性的异质性有关。基于总结的证据，综述的最后一部分讨论了在药物处方前检测与TNFi反应相关的药物遗传变体的潜在临床应用，并探讨了实现TNFi使用者个性化治疗的未来方向。
