IBD Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy.
Gastroenterology Unit, Anna Meyer Childrens Hospital, Department of Paediatrics, University of Firenze, Firenze, Italy.
Int J Immunopathol Pharmacol. 2014 Jan-Mar;27(1 Suppl):11-32. doi: 10.1177/03946320140270S102.
The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.
免疫介导的炎症性疾病(IMIDs)的复杂发病机制已经得到了广泛的研究,细胞因子的失调,如肿瘤坏死因子(TNF),被认为在各种 IMIDs 的发病机制中起着主导作用,如类风湿关节炎、强直性脊柱炎、克罗恩病、溃疡性结肠炎、银屑病和银屑病关节炎。随后开发出能够阻断 TNF 的生物制剂,这使得这些疾病的药物治疗取得了重要进展,并证实了 TNF 在 IMIDs 中具有主要作用的共同病理生理学概念。目前已经有五种 TNF 抑制剂被批准用于治疗一种或多种 IMIDs;这些包括英夫利昔单抗、依那西普、阿达木单抗、戈利木单抗和 Certolizumab pegol。鉴于 IMIDs 的发病机制背景相似,人们可能期望抗 TNF 药物具有类似的疗效和可耐受性;然而,情况可能并非如此。抗 TNF 药物之间的结构和药理学差异可能导致不同的 IMIDs 中药物的疗效和耐受性存在差异,以及效力、治疗剂量范围、给药方案、给药途径和免疫原性倾向的差异。在五种批准用于治疗 IMIDs 的 TNF 抑制剂中,阿达木单抗的适应证最广泛。阿达木单抗在广泛的适应证中表现出优异的疗效和耐受性的对照临床试验数据,得到了来自观察性研究的真实世界长期数据的支持,这些数据证实了阿达木单抗作为 IMIDs 管理的合适选择的价值。