Pediatric Rheumatology Unit of Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade São Paulo University, São Paulo, Brazil.
Clin Rev Allergy Immunol. 2010 Apr;38(2-3):82-9. doi: 10.1007/s12016-009-8140-3.
Prognosis of several autoimmune diseases, especially rheumatoid arthritis (RA), ankylosing spondylitis, Crohn's disease (CD), and psoriasis, usually refractory to conventional treatment improved considerably with the introduction of tumor necrosis factor alpha (TNF-alpha) antagonistic agents, which is now available (infliximab, etanercept, and adalimumab). However, a portion of patients persists with active disease, infusion reactions, and relapses even during current biological therapy. One of the reasons for this is the associated immunogenicity to these drugs. The incentive for induction of antibodies against anti-TNF-alpha agent depends mainly on its constitution. Chimerical drugs have a higher capacity of inducing immunogenicity compared to completely human drugs. Among the three anti-TNF-alpha agents, this phenomenon has been studied mainly in patients using infliximab, especially in RA and CD. The prevalence of anti-infliximab antibodies in RA varies from 12% to 44% and seems to be inversely proportional to the level of seric infliximab and therapeutic response. The use of etanercept was associated to the development of anti-etanercept antibodies in 0% to 18% of patients, without apparent effect on effectiveness or adverse events. Studies with RA and CD patients show prevalence of anti-adalimumab antibodies from 1% to 87%. Immunosuppressive drug addiction can reduce the induction of anti-TNF-alpha antibodies.
几种自身免疫性疾病的预后，尤其是类风湿关节炎（RA）、强直性脊柱炎、克罗恩病（CD）和银屑病，通常对常规治疗反应不佳，但肿瘤坏死因子-α（TNF-α）拮抗剂的引入使病情得到了显著改善，目前有多种此类药物可供使用（英夫利昔单抗、依那西普和阿达木单抗）。然而，即使在当前的生物治疗中，仍有一部分患者疾病持续活动、出现输注反应和复发。造成这种情况的原因之一是这些药物的免疫原性。诱导针对抗 TNF-α药物的抗体的诱因主要取决于其结构。嵌合药物比完全人源化药物具有更高的免疫原性。在三种抗 TNF-α药物中，这种现象主要在使用英夫利昔单抗的患者中进行了研究，尤其是在 RA 和 CD 中。RA 患者中抗英夫利昔单抗抗体的患病率为 12%至 44%，似乎与血清英夫利昔单抗水平和治疗反应呈反比。使用依那西普与 0%至 18%的患者中出现抗依那西普抗体有关，但对疗效或不良事件无明显影响。RA 和 CD 患者的研究显示，抗阿达木单抗抗体的患病率为 1%至 87%。免疫抑制剂的成瘾性可以降低抗 TNF-α抗体的诱导。
