ANTI TNF CHIMERIC MONOCLONAL ANTIBODY IN PATIENTS WITH RHEUMATOID ARTHRITIS

目前风湿性关节炎的治疗包括疾病早期的非甾体抗炎药（NSAIDs），随着疾病的逐渐恶化，最终让位于口服类固醇和改善疾病的抗风湿性药物（DMARDs）。甲氨蝶呤（MTX）已成为许多风湿病学家的首选DMARD，因为它的作用模式更快，长期使用的记录更好。然而，尽管使用了高剂量的甲氨蝶呤，许多患者只经历部分症状缓解，仍然有活动性疾病的特征。实验证据表明TNF在RA的病理生物学中是一个重要的介质，并强调TNF是一个合适的治疗靶点。嵌合A2 （cA2）是一种单克隆抗体，具有高亲和力和特异性与人TNF结合并中和其生物活性。目前的试验旨在在更大的患者群体（n=300）中显示，尽管MTX治疗，但给予长达一年的cA2将为活动性RA患者提供快速和持续的临床体征和症状减轻。将评估四个钙治疗组，并与安慰剂组进行比较。本研究的主要终点将是治疗开始后30周RA的临床体征和症状的减少。体征和症状的持续减少，以及残疾、关节损伤、疾病缓解和生活质量将在1年时进行评估。

Current therapy for Rheumatiod arthritis comprises non-steroidal anti-inflammatory drugs (NSAIDs) in early stages of the disease, ultimately given way to oral steroids and the disease-modifying anti-rheumatic drugs (DMARDs) as the disease progressively worsens. Methotrexate (MTX) has become the DMARD of choice of many rheumatologists because of its faster mode of action and better record of prolonged use. However, despite the use of high doses of MTX, many patients only experience partial relief of symptoms and still have features of active disease. Experimental evidence implicates TNF as an important mediator in the pathobiology of RA and underscores TNF as an appropriate therapeutic target. Chimeric A2 (cA2) is a monoclonal antibody that binds with high affinity and specificity to human TNF and neutralizes its biologic activity. The current trial is designed to show in a larger patient population (n=300) that cA2 given for up to one year will provide a rapid and sustained reduciton of clinical signs and symptoms of RA in patients who have active RA despite MTX therapy. Four cA2 treatment groups will be evaluated and compared to a placebo group. The primary endpoint in this study will be a reduction in the clinical signs and symptoms of RA at 30 weeks following the onset of treatment. Continuing reduction in signs and symptoms, as well as disability, joint damage, disease remission and quality of life will be evaluated at 1 year.