The Hunter Humira and Endothelial Function in Early Rheumatoid Arthritis Trial

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Introduction Rheumatoid arthritis is a severe destructive inflammatory arthritis that affects 1.5% of the population. The anti-CCP antibody positive subgroup experience a 50% increased risk of cardiovascular events that is directly related to the disease process although the mechanisms of this remain unclear. There is mounting evidence that a “window of opportunity” exists during which time treatment is more likely to achieve remission. It therefore seems possible that a similar window of opportunity might exist for the treatment of vascular disease in rheumatoid arthritis. New effective treatments for rheumatoid arthritis called the "Biologics" have become widely available over the last decade. This has resulted in dramatic improvements in the treatment of the arthritis. However, it remains unclear whether these treatments influence the risk of cardiovascular events. Pooled analyses of the large trials have not had sufficient power and are of insufficient duration to answer this question. Meta-analysis of the combined registry data found dramatic differences in the TNF-inhibitor treated group but these effects may be explained by confounding. Studies using assessments of pre-clinical vascular disease using imaging and physiological assessments of arterial stiffness seem more likely to show treatment effects but have thus far been inconclusive. Based upon studies in hypertension it is likely that studies utilising assessments of arterial stiffness and carotid artery wall thickness would require randomised controlled trials of considerable size and duration to detect treatment effects. Earlier pathological processes in vascular disease such as endothelial dysfunction are more likely to change quickly and detectably in response to treatment. However, studies have been inconclusive possibly due to the small sample sizes, insufficient study duration and because the studies evaluated subject with established and possibly irreversible disease. The Australian PBS funds Biologic drugs for patients with rheumatoid arthritis only after they have failed to respond to 6 months conventional DMARD therapy. This 6 month period presents an opportunity to evaluate the effects of TNF-inhibition (with adalimumab) upon vascular function in a randomised controlled trial while at the same time enhancing patient care. This phase 2, single-centre, double-blind randomised, placebo-controlled study will evaluate the effects of adalimumab upon endothelial function in early and established anti-CCP positive rheumatoid arthritis. Methods Two groups will be studied in a randomised, controlled trial: 1. 30 subjects with Early Anti-CCP Positive Rheumatoid Arthritis (<12 months disease duration, age 18-50 years) and ; 2. 30 subjects with Established Anti-CCP Positive Rheumatoid Arthritis (>12 mths disease duration, age>18 years) Subjects within each group will be randomised 1:1 to receive adalimumab / placebo for 24 weeks in addition to "usual care”.