Semerano Luca, Boissier Marie-Christophe
Université Paris 13, EA4222, Li2P, Bobigny, France.
Med Sci (Paris). 2009 Dec;25(12):1108-12. doi: 10.1051/medsci/200925121108.
Among chronic inflammatory diseases, rheumatoid arthritis is a common inflammatory and destructive arthropathy, characterized by the release of potent proinflammatory cytokines mostly TNFa and IL-1, which both mediate systemic effects and contribute to joint destruction. Many therapeutic agents have been proposed to antagonise these cytokines, among which monoclonal antibodies. Thus twenty years ago the anti-TNFa infliximab was the first monoclonal antibody to be proposed in a non-cancerous indication, rheumatoid arthritis. Since then, several other monoclonal antibodies and/or antagonists either targeting cytokines (IL-1, IL-6, RANKL), but also immune cellular effectors T and B cells, have been evaluated not only in rheumatoid arthritis, but also in systemic lupus, Crohn's disease, multiple sclerosis, or ankylosing spondylitis. Clinical benefit has been unambiguously demonstrated, but before these novel molecules enter routine clinical practice, several parameters will have to be accurately documented such as their safety, long term efficacy, and economical cost.
在慢性炎症性疾病中,类风湿性关节炎是一种常见的炎症性和破坏性关节病,其特征是释放主要为肿瘤坏死因子α(TNFα)和白细胞介素-1(IL-1)的强效促炎细胞因子,这两种细胞因子都介导全身效应并导致关节破坏。已经提出了许多治疗药物来拮抗这些细胞因子,其中包括单克隆抗体。因此,二十年前抗TNFα的英夫利昔单抗是首个被提出用于非癌症适应症——类风湿性关节炎的单克隆抗体。从那时起,其他几种单克隆抗体和/或拮抗剂,不仅靶向细胞因子(IL-1、IL-6、核因子κB受体活化因子配体(RANKL)),还靶向免疫细胞效应物T细胞和B细胞,已在类风湿性关节炎中进行了评估,也在系统性红斑狼疮、克罗恩病、多发性硬化症或强直性脊柱炎中进行了评估。临床获益已得到明确证明,但在这些新型分子进入常规临床实践之前,必须准确记录几个参数,如它们的安全性、长期疗效和经济成本。