Licastro F, Chiappelli M, Ianni M, Porcellini E
Department of Experimental Pathology, School of Medicine, University of Bologna, Bologna, Italy.
Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):567-72. doi: 10.1177/039463200902200302.
Inhibitors of tumor necrosis factor-alpha have deeply changed the therapy of several inflammatory human diseases. For instance, clinical management of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have profoundly benefited after the introduction of new therapeutic tools, such as antagonist of TNF-alpha molecule. These drugs include etanercept, a soluble TNF-alpha receptor antagonist, three anti-TNF-alpha antibodies, adalimumab, infliximab, golimumab and certolizumab a humanized Fab fragment combined with polyethylene glycol. These compounds efficiently inhibit several TNF-alpha biological-mediated effects, however, they have also shown differential clinical efficacy in several trials from different autoimmune diseases. It is of clinical relevance that non-responders to one of these drugs often positively responded to another. Different mechanisms of action and diversity in pharmacokinetics of these three compounds may partially explain different clinical effects. However, partially diverse pathogenetic mechanisms in different diseases also contribute to differential therapeutic responses. Therefore, these apparently homogeneous agents can not be considered equivalent in their clinically efficacy. Differential therapeutic actions of these drugs may be advantageously used in clinical practice and further improve the great potential of individual TNF-alpha inhibitors.
肿瘤坏死因子-α抑制剂已深刻改变了多种人类炎症性疾病的治疗方法。例如，在引入新的治疗手段（如肿瘤坏死因子-α分子拮抗剂）后，类风湿性关节炎、银屑病关节炎和强直性脊柱炎的临床治疗受益匪浅。这些药物包括依那西普（一种可溶性肿瘤坏死因子-α受体拮抗剂）、三种抗肿瘤坏死因子-α抗体（阿达木单抗、英夫利昔单抗、戈利木单抗）以及赛妥珠单抗（一种与聚乙二醇结合的人源化Fab片段）。这些化合物能有效抑制多种肿瘤坏死因子-α生物学介导的效应，然而，在针对不同自身免疫性疾病的多项试验中，它们也显示出了不同的临床疗效。具有临床相关性的是，对其中一种药物无反应的患者往往对另一种药物有积极反应。这三种化合物不同的作用机制和药代动力学差异可能部分解释了不同的临床效果。然而，不同疾病中部分不同的发病机制也导致了不同的治疗反应。因此，这些表面上同类的药物在临床疗效上不能被视为等同。这些药物不同的治疗作用可在临床实践中得到有益应用，并进一步提升各个肿瘤坏死因子-α抑制剂的巨大潜力。
