Rheumatoid arthritis (RA) is a chronic inflammatory condition of unknown etiology for which there is no cure. It is one of the most disabling diseases and affects about 1% of the world‟s population. Recent developments in the field of molecular biology have resulted in the production of new drugs used in the treatment RA. Despite these advancements, achieving optimal disease control and prevention of disease progression is still difficult in many patients, leading to a continued search for treatment methods that will improve patient outcomes. Non-biologic forms of treatment that are still being investigated include the use of statins as an adjunct therapy due to their reported antiinflammatory effects. Some studies have shown that the use of statins in patients with RA help in reducing disease activity and swollen joint count in addition to lowering cardiovascular risk. As evidence continue to increase on the anti-inflammatory effect of statins, researchers have started investigating possible benefits that may result from the use of statins in treatment of RA, a chronic disease marked by high levels of systemic and local inflammation. This study investigated the anti-inflammatory effect of statins in rheumatoid arthritis patients with associated risks for cardiovascular disease, using simvastatin as the investigational product. Patients with moderately active RA despite being on maximum disease-modifying antirheumatic drugs (DMARDs) therapy and having associated risks for cardiovascular disease were screened for the study. Eligible patients were randomized into two groups, 1 and 2. Patients in group 1 received simvastatin treatment (20mg/day) for a period of 3 months in addition to their usual DMARDs after which they stopped simvastatin treatment and were followed up for a further 3 months off simvastatin treatment. Those in group 2 were allowed to continue on their usual DMARDs without simvastatin treatment for the first 3 months of the study after which they received 20mg/day simvastatin for a period of 3 months in addition to their usual DMARDs. The anti-inflammatory effect of simvastatin was assessed by monitoring the inflammatory variables; erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) and disease activity in the two groups at screening, at the crossover point and at end of the study. Disease activity was significantly reduced with simvastatin treatment in the two groups. The mean change in disease activity score with simvastatin treatment was 1.30 (p = 0.01) in group 1 and 1.74 (p = 0.01) in group 2. ESR was significantly reduced with simvastatin treatment in group 1 with a mean change of 19.0 (p = 0.005) and marginally reduced in group 2 with a mean change 26.0 (p = 0.09). There was no significant change in CRP with simvastatin treatment in the two groups. The mean change in CRP with simvastatin treatment was 7.0 (p = 0.24) in group 1 and 14.7 (p =0.20) in group 2. All the patients benefited from the lipid-lowering effect of simvastatin. These findings suggest that statins may have mild anti-inflammatory properties and will be good adjuvant in RA patients with associated risks for cardiovascular disease. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Pharmacology / unrestricted