Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Mycophenolate Mofetil and Hydroxychloroquine but Not Azathioprine Improve HDL Function in Women with SLE.
McMahon3, Maureen, Grossman4, Jennifer M., Gomez3, Jessica, Sahakian3, Lori, Chen3, Weiling, Fitzgerald3, John, Skaggs2, Brian
Oklahoma Med Research Foundation, Oklahoma City, OK
UCLA, Los Angeles, CA
UCLA School of Medicine, Los Angeles, CA
University of California Los Angeles, Sherman Oaks, CA
University of California Los Angeles School of Medicine, Los Angeles, CA
Women with SLE have an unexplained increase in CAD compared to controls. Normal HDL protects against plaque by preventing oxidation of LDL and the resulting inflammatory response. Pro-inflammatory HDL (piHDL) are abnormal HDL that cannot protect LDL from oxidation. We previously reported that 45% of SLE women vs. 5% of controls have piHDL In addition, SLE patients with piHDL are 16 times more likely to have plaque on carotid ultrasound than patients with normal functioning HDL. SLE function is stable over time; however, it is unknown how disease modifying agents affect HDL function.
This prospective observational study included any SLE subject from our cohort who was started on a new immunosuppressive agent. Cryopreserved plasma samples were taken at three time points: baseline (prior to initiation of drug), 6 weeks, and 12 weeks post initiation of therapy. To determine the antioxidant function of HDL, we measured change in fluorescence intensity caused by oxidation of DCFH by OxLDL in the presence or absence of test HDL. Fluorescence in the absence of HDL was normalized to 1.0. Values greater than 1.0 after the addition of HDL indicated piHDL. (In previously published studies, mean HDL function in healthy controls ranges from0.44 to 0.66).
13 subjects were started on mycophenolate (MMF), 11 subjects on azathioprine (AZA), and 22 subjects on hydroxychloroquine (HCQ). The mean SLEDAI score at baseline was 8.9 ± 5.4 in the MMF group vs. 9.2 ± 4.1 in AZA vs. 6.4 ± 3.2 in HCQ (p=ns among all groups). In MMF treatedsubjects, HDL function improved from baseline, with a score of 2.18 ± 1.46 prior to therapy dropping to 1.28 ± 0.87 after 6 weeks of therapy (p=0.04,paired t-test), and to 0.89 ± 0.56 after 12 weeks of therapy (p=0.02). In hydroxychloroquine treated subjects, HDL function did not significantly change from baseline at 6 weeks of therapy from 1.66 ± 1.16 to 1.31 ± 1.27 (p=0.19 ); however, it did significantly improve after 12 weeks of therapy, 0.96 ± 0.71(p=0.027). In those treated with azathioprine, HDL function remained relatively stable (1.07 ± 0.53) vs. 1.30 ± 0.77 at 6 weeks (p=ns), and 1.00 ± 0.99 at 12 weeks (p=ns). In addition, there was a trend towards a correlation between change in HDL function and improvement in SELENA-SLEDAI in all groups, (r=0.367, p=0.09), although this did not reach statistical significance.
In conclusion, HDL function is significantly improved by therapy with mycophenolate mofetil, although not to normal levels. There was also improvement with hydroxychloroquine, but not with azathioprine.
To cite this abstract, please use the following information:
McMahon, Maureen, Grossman, Jennifer M., Gomez, Jessica, Sahakian, Lori, Chen, Weiling, Fitzgerald, John, et al; Mycophenolate Mofetil and Hydroxychloroquine but Not Azathioprine Improve HDL Function in Women with SLE. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2241