Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Randomised Controlled Trial of Mycophenolate Mofetil Versus Placebo On Surrogate Markers of Atherosclerosis in Systemic Lupus Erythematosus
Davies, R., Sangle, SR., Murru, V., Bertolaccini, ML., Khamashta, Munther A., D'Cruz, David P.
Systemic lupus erythematosus (SLE) is an independent risk factor for atherosclerosis. Endothelial dysfunction is the earliest marker of atherosclerosis and is measured by flow mediated dilation (FMD) of the brachial artery. The purpose of the study was to measure FMD in mild, stable SLE patients and look for change in FMD with the immunosuppressant drug mycophenolate mofetil (MMF).
A prospective, double-blind, randomised, placebo-controlled trial evaluating MMF on surrogate markers of atherosclerosis in mild SLE. 70 females fulfilling ACR criteria were recruited and allocated by minimisation to either placebo or MMF 1gm bd for 8 weeks. The primary end point was change in FMD assessed on an intention to treat basis. Other inclusion criteria were mild and stable disease, 1860 years, on hydroxychloroquine and/or <=15mgs prednisolone od. Exclusions were severe active disease, other immunosuppressants, smokers, diabetes mellitus and ischaemic heart, cerebrovascular or end stage renal disease. A minimum of 30 subjects per group were required to detect a change in FMD with a power of 90% at a 5% significance level.
Seventy patients were recruited and 63 completed the study. The FMD for both groups was within the normal range at baseline and failed to change significantly post treatment. There was a significant decrease in BILAG score within the treatment group and this was reflected by a downward trend in Hs-CRP levels, although not reaching statistical significance. The Hs-CRP rose significantly during the study period in the placebo group. Secondary end points looked at change in levels of serum biomarkers previously shown to be associated with increased cardiovascular risk (ADMA) and endothelial dysfunction (tPA and PAI-1), however levels failed to change in either group and using multiple regression analysis there were no assoiciations with reduced FMD or traditional cardiovascular risk factors.
|Placebo visit 1||Placebo visit 2||p values||MMF visit 1||MMF visit 2||p value|
|FMD%||7.61 (±3.48)||7.29 (±3.21)||8.36 (±4.11)||8.98 (±5.47)|
|BILAG||9.8 (±4.2)||9.5 (±4)||10.1 (±4.5)||8.5 (±3.9)||p=0.03|
|HsCRP||5.1 (±5.8)||7.4 (±9.7)||p=0.05||6.3 (±8.6)||5.8 (±7.4)|
|ADMA||0.39 (±0.23)||0.38 (±0.16)||0.36 (±0.22)||0.35 (±0.17)|
|tPA||16.03 (±||19.83 (±||29.33 (±||18.39 (±|
|PAI-1||23.07 (±20.12)||23.08 (±19.98)||21.35 (±14.56)||23.29 (±12.55)|
|Values; mean(±sd), BILAG; British Isles Lupus Assessment Group disease activity score, HsCRP; high sensitivity C-reactive protein (mg/l), ADMA; Asymmetric dimethylarginine (mmol/l), tPA; Tissue plasminogen activator (ng/ml), PAI-1; Plasminogen activator inhibitor 1 (ng/ml).|
Endothelial function is well preserved In SLE patients with mild, stable disease on hydroxychloroquine and with few or absent traditional cardiovascular risk factors. It is likely that aggressive immunosuppressive treatment to suppress vascular inflammation may not be warranted in these patients.
To cite this abstract, please use the following information:
Davies, R., Sangle, SR., Murru, V., Bertolaccini, ML., Khamashta, Munther A., D'Cruz, David P.; A Randomised Controlled Trial of Mycophenolate Mofetil Versus Placebo On Surrogate Markers of Atherosclerosis in Systemic Lupus Erythematosus [abstract]. Arthritis Rheum 2009;60 Suppl 10 :561