ANTI TNF CHIMERIC MONOCLONAL ANTIBODY IN PATIENTS WITH RHEUMATOID ARTHRITIS

目前风湿性关节炎的治疗方法包括疾病早期的非类固醇抗炎药(NSAIDs)，随着疾病的逐渐恶化，最终被口服类固醇和修改疾病的抗风湿药物(DMARDS)所取代。甲氨蝶呤(MTX)因其更快的作用模式和更好的长期使用记录而成为许多风湿科医生的DMARD选择。然而，尽管使用了大剂量的MTX，许多患者只经历了症状的部分缓解，仍然具有活动性疾病的特征。实验证据表明，肿瘤坏死因子在类风湿关节炎的病理生物学中是一个重要的介体，并强调了肿瘤坏死因子是一个合适的治疗靶点。嵌合体A2(CA2)是一种能与人肿瘤坏死因子高度亲和力和特异性结合并中和其生物学活性的单抗。目前的试验是为了在更大的患者群体(n=300)中表明，服用长达一年的CA2将迅速和持续地减少尽管接受MTX治疗的活动期RA患者的RA的临床症状和体征。将对四个CA2治疗组进行评估，并与安慰剂组进行比较。这项研究的主要终点将是在治疗开始后30周时类风湿性关节炎的临床症状和体征的减少。持续减少的体征和症状，以及残疾、关节损伤、疾病缓解和生活质量将在1岁时进行评估。

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.