ANTIBIOTIC THERAPY FOR RHEUMATOID ARTHRITIS (ATRA TRIAL)

之前的随机对照临床试验表明，口服 四环素类药物可减轻小鼠关节炎症症状 类风湿关节炎(RA)。这类抗生素已经被很好地描述 抑菌效果以及抗胶原酶活性。胶原酶 是一种降解软骨和骨骼的酶，据信 在类风湿关节炎的发病机制中起重要作用。本研究对其安全性进行了评价。 静脉注射多西环素治疗60例的潜在临床疗效 类风湿性关节炎患者，并将探索关节炎是否有任何改善 多西环素是由于其抗菌作用或能力 降低胶原酶活性。 这项研究的三个目标是：1)确定可行性， 多西环素静脉给药的安全性和潜在临床疗效 RA，并探讨该药是否能改善临床表现 通过抑制细菌感染或基质来治疗这种疾病 金属蛋白酶(MMPs)活性；2)测定每日和 每周静脉注射多西环素可减少尿液排泄量 类风湿关节炎患者的胶原交联物和潜在的关节延迟 损害；3)探索每日和每周静脉注射的潜在影响。 多西环素治疗对软骨蛋白多糖生化标志物的影响 退化。 患者将被随机分为3组：I组接受静脉注射。 多西环素和口服安慰剂，II组将接受静脉注射安慰剂和 口服阿奇霉素，第三组接受静脉注射和口服安慰剂。这个 静脉注射治疗将通过外周长线导管进行。 最初的治疗阶段包括每日输液和口服治疗。 已经21天了。第二个治疗阶段包括每周输液。 从第4周到第11周。

Previous randomized, controlled clinical trials suggest that oral tetracyclines may reduce the symptoms of joint inflammation in rheumatoid arthritis (RA). This class of antibiotics has well-described antimicrobial effects as well as anti-collagenase activity. Collagenase is an enzyme that degrades cartilage and bone and is believed to be important in the pathogenesis of RA. This study evaluates the safety and potential clinical efficacy of I.V. doxycycline therapy in 60 patients with RA and will explore whether any improvements in arthritis from the doxycycline are due to its antibacterial actions or ability to reduce the activity of collagenase. The three objectives of this study are: 1) To determine the feasibility, safety, and potential clinical efficacy of I.V. doxycycline therapy in RA and explore whether this agent ameliorates clinical manifestations of this disease by suppressing bacterial infection or matrix metalloproteinases (MMP) activity; 2) To determine whether daily and weekly treatment with I.V. doxycycline can reduce urinary excretion of collagen crosslinks in patients with RA and potentially retard joint damage; and 3) To explore the potential effects of daily and weekly I.V. doxcycline therapy on biochemical markers of cartilage proteoglycan degradation. Patients will be randomized into 3 groups: Group I receives I.V. doxycycline and oral placebo, Group II will receives I.V. placebo and oral azithromycin, and Group III receives I.V. and oral placebo. The I.V. therapy will be delivered through a peripheral long-line catheter. The initial treatment phase consists of daily infusions and oral therapy for 21 days. The second treatment phase consists of weekly infusions administered from week 4 through 11.