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英夫利昔单抗用于治疗早期类风湿性关节炎。

Infliximab for the treatment of early rheumatoid arthritis.

作者信息

Geletka Robin C, St Clair E William

机构信息

Duke University Medical Centre, Division of Rheumatology and Immunology, Department of Medicine, Box 2918, Durham, NC 27710, USA.

出版信息

Expert Opin Biol Ther. 2005 Mar;5(3):405-17. doi: 10.1517/14712598.5.3.405.

Abstract

Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease characterised predominately by polyarthritis with frequent progression to permanent joint damage and disability. Evidence shows that starting treatment with disease-modifying antirheumatic drug (DMARD) therapy early in the course of disease can slow radiographic progression of RA compared with a more delayed approach. Moreover, in the early stages of RA, treatment with a combination of methotrexate (MTX), a traditional DMARD, and a biologic with tumour necrosis factor (TNF)-alpha blocking activity has proven to be more effective than using MTX alone. Among the approved TNF-alpha inhibitors, infliximab is a chimeric monoclonal antibody with high affinity and specificity for its target cytokine. It binds to soluble TNF monomers and trimers, as well as membrane-bound TNF-alpha, forming a stable complex which prevents TNF-alpha from binding to its receptor and triggering a biological response. The combination of MTX and infliximab therapy has shown superior clinical outcomes compared with MTX monotherapy in early RA, as well as greater protection against joint damage and physical disability. Although infliximab therapy has been associated with side effects, including serious infections, this drug can be administered with an acceptable margin of safety for several years by appropriate selection of patients, screening for latent and active tuberculosis, and monitoring of patients for infection and other toxicities. The knowledge of the benefits of infliximab therapy for early RA affords groundwork for developing more effective treatment strategies that can minimise disease progression over the long term.

摘要

类风湿关节炎(RA)是一种全身性慢性炎症性疾病,主要特征为多关节炎,常进展为永久性关节损伤和残疾。有证据表明,与延迟治疗相比,在疾病早期开始使用改善病情抗风湿药物(DMARD)治疗可减缓RA的影像学进展。此外,在RA的早期阶段,传统DMARD甲氨蝶呤(MTX)与具有肿瘤坏死因子(TNF)-α阻断活性的生物制剂联合治疗已被证明比单独使用MTX更有效。在已获批的TNF-α抑制剂中,英夫利昔单抗是一种嵌合单克隆抗体,对其靶细胞因子具有高亲和力和特异性。它与可溶性TNF单体和三聚体以及膜结合TNF-α结合,形成稳定的复合物,阻止TNF-α与其受体结合并触发生物学反应。在早期RA中,MTX与英夫利昔单抗联合治疗已显示出优于MTX单药治疗的临床疗效,以及对关节损伤和身体残疾的更强保护作用。尽管英夫利昔单抗治疗与包括严重感染在内的副作用相关,但通过适当选择患者、筛查潜伏性和活动性结核病以及监测患者的感染和其他毒性反应,该药物可在数年内以可接受的安全范围给药。英夫利昔单抗治疗早期RA的益处的相关知识为制定更有效的治疗策略奠定了基础,这些策略可长期最大限度地减少疾病进展。

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