ANTIBIOTIC THERAPY FOR RHEUMATOID ARTHRITIS (ATRA TRIAL)

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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; and 4) to determine whether IV doxycycline can reduce expression of nitric oxide synthase type 2 expressed by circulatory monocytes.