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An open-label, randomized, crossover study to assess anti-inflammatory effect of Simvastatin in Rheumatoid Arthritis statin-naïve patients with associated risk factors for cardiovascular disease

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

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:up/oai:repository.up.ac.za:2263/40713
Date January 2013
CreatorsKomolafe, Ayoola Oluwakayode
ContributorsGreeff, O.B.W. (Oppel Bernhardt Wilhelm), 1948-, aykoma@yahoo.co.uk, Ally, Mahmood Moosa Tar Mahomed
PublisherUniversity of Pretoria
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
TypeDissertation
Rights© 2013 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.

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