Mycophenolate Mofetil (MMF) Does Not Slow the Progression of Subclinical Atherosclerosis in SLE Over 2 Years

Rheumatol Int. 2012 Sep;32(9):2701-5. doi: 10.1007/s00296-011-2048-y. Epub 2011 Jul 27.

Abstract

Accelerated atherosclerosis is a major cause of mortality in SLE. Mycophenolate mofetil (MMF) has been shown to suppress growth factor-induced proliferation of vascular smooth muscle and endothelial cells in animal models. We hypothesized that MMF might modify the inflammatory component of atherosclerosis in SLE. We examined the effect of MMF on atherosclerosis as measured by changes in carotid intima-media thickness (IMT) or coronary artery calcium (CAC) over 2 years. CAC and carotid IMT were measured at baseline and 2 years later in a cohort of 187 patients with SLE. The cohort was 91% women, 59% Caucasian, and 35% African-American, with a mean age of 45 ± 11 years. Of these, 12.5% (n = 25) received MMF during follow-up. The daily dose ranged from 500 to 3,000 mg/day, and duration ranged from 84 days to the entire 2 years. We divided MMF users into three groups: low exposure (<1,500 mg average daily dose), high exposure (≥1,500 average daily dose), and any exposure of MMF (<1,500 or ≥1,500 average daily dose) for 2 years. The mean CAC increased in all four groups: no MMF: 1.17-1.28, low MMF: 1.02-1.13, high MMF: 1.44-1.61, and any MMF: 1.21-1.34 log-Agatston units. Compared to no MMF, there was no statistically different change between the three groups (p = 0.99, 0.87, and 0.91). Similarly, mean carotid IMT increased in all four groups: no MMF: 0.58-0.66, low MMF: 0.55-0.60, high MMF: 0.56-0.71, and any MMF: 0.56-0.66. We then adjusted for statin use, lupus nephritis, body mass index, systolic blood pressure, cholesterol, and age during the 2-year follow-up. The association between MMF exposure and change in CAC or carotid IMT was not statistically significant (p = 0.63 for CAC, and p = 0.085 for carotid IMT). There was no evidence that MMF slowed or decreased the progression of atherosclerosis as measured by carotid IMT or CAC. Because the number of patients taking MMF was only twenty-five, larger studies for longer time periods are needed to explore any effect of MMF on subclinical atherosclerosis in SLE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcium / metabolism
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / drug therapy*
  • Carotid Artery Diseases / etiology*
  • Carotid Intima-Media Thickness
  • Cohort Studies
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / metabolism
  • Coronary Vessels / metabolism
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Longitudinal Studies
  • Lupus Erythematosus, Systemic / complications*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Calcium