Systemic Lupus Erythematosus
Abstract 1267 Treatment of Active Systemic Lupus Erythematosus (SLE) with the Prolactin (PRL) Lowering Drug, Bromocriptine (BC): Comparison with Hydroxychloroquine (HC) in a Randomized, Blinded One-year Study.
Sara E. Walker , Geetha H. Reddy, D Miller, D Yangco, S Kalanje, N I Abdou, K A Huston, Ann E Warner, W D Bronson Columbia, MO, Kansas City, MO, St. Joseph, MO
Bromocriptine has been studied in animal models, open-label series, and in clinical trials versus placebo, and found to have benefit for SLE.
In this double-blind trial, it was compared with hydroxychloroquine. Analyses were done in two ways: pre vs. post within each group, and between the two groups. The two groups were comparable at baseline. Patients did not have an elevated prolactin to enter.
In the between group analyses, the two drugs appeared to be comparable in efficacy. However, the pre vs. post analyses suggested superiority of hydroxychloroquine. In the pre vs. post analyses, bromocriptine treated patients improved on the SLAM activity score, but not the SLEDAI. SLAM contains many subjective descriptors, such as fatigue and headache. It was the opinion of Dr. Walker that many of these subjective measures improved. She did not have information on which patients had fibromyalgia.
Editorial Comment: In summary, this study further supports a role for bromocriptine in the treatment of lupus. It does not suggest, however, that the drug is superior to hydroxychloroquine.
Abstract 1395 Mycophenolate Mofetil Treatment of Systemic Lupus Erythematosus
M Petri Baltimore, MD.
There is a great need for additional immunosuppressive drugs to treat SLE. Mycophenolate mofetil (Cellcept) has shown promise in animal models and in several series of patients with lupus nephritis (Briggs et al; Dooley et al). In this series, 22 patients with moderate-to-severe SLE of all types were included.
Cellcept was begun at 1000mg bid, and if there was no response at 1 month, increased to 1000mg tid. These doses were well tolerated, with only a few dropouts: 1 for fever, 1 for depression, and 1 for diarrhea. Response to cellcept began at 1 month but continued thereafter. Significant improvement was shown in multiple measures of disease activity, prednisone dose, and serologies.
However, when the group with renal disease was examined separately, compete responses (using the NIH definition of 24 hour urine protein less than 1000mg) were rare. 24-hour urine protein decreased on average about 50% (4 grams to 2 grams) but failed to reach statistical significance.
Editorial Comment: In conclusion, this series suggests that cellcept can now be added to the list of other well tolerated immunosuppressive drugs in SLE (methotrexate, imuran) but caution is advised since cellcept may not be as efficacious as cytoxan for renal disease. A head-to-head study for DPGN (diffuse proliferative glomerulonephritis) is now underway, under the direction of Dr. Ellen Ginzler.
Abstract 597 High-Dose Immunoblative Cyclophospamide (HDIC) in SLE.
M Petri, A Jones, R Brodsky Baltimore, MD.
Brodsky et al published long-term follow-up of high dose immunoblative cytoxan for aplastic anemia, showing 7 out of 10 complete remissions without bone marrow transplant. Stem cells survive HDIC because they possess an enzyme ALDH that metabolizes cytoxan. HDIC is the usual preparative regimen for stem cell transplantation; therefore, this suggests that the reason that stem cell transplant shows benefit for SLE may not be the stem cell transplant but the preparatory regimen itself.
In this series of 11 SLE patients treated with HDIC, all had failed multiple immunosuppressive regimens. Of six patients with renal disease, 3 had a complete response and 1 a partial response; of three patients with CNS-SLE, one had a complete response and 2 a partial response; of two patients with dermatological lupus, 1 had a complete response and 1 a partial response. The complete responses have been durable, with some lasting for two and a half years. Even the partial responses have been impressive, with some patients continuing to respond for 18 months after the HDIC.
Editorial Comment: NIAMS is now funding a comparative trial of HDIC versus the NIH IV cytoxan protocol for SLE patients with moderate-to-severe SLE who have not yet had cytoxan.
Abstract 1232 Follow-up Assessment of Atherosclerotic Vascular Disease Using Duplex Scanning in Women with SLE
S.G. Fitzgerald, K Sutton-Tyrrell, L Kuller, S Manzi Pittsburgh, PA.
Dr. Manzi and colleagues have previously shown that 35% of their SLE patients have atherosclerotic carotid plaque. This is over twice the frequency we have observed at Johns Hopkins. However, both groups agree that premature atherosclerosis is the most important long-term morbidity issue in SLE -- and that noninvasive means of detection are essential.
In this study, 55 women underwent a follow-up carotid duplex approximately 2 years after the first. 31% had an increase in plaque (p<.001). Predictive variables included age, post-menopausal status, fibrinogen, pulse pressure, and race (although 95% of the patients were caucasian). The best predictor was higher fibrinogen level at baseline.
Editorial Comment: This important study is instructive more for the factors that were NOT predictive: hypertension and hyperglycemia -- since these are the factors most amenable to intervention. It could not address whether fibrinogen is stable over time in SLE patients. It also could not address whether statins and estrogen replacement are protective. These important issues point out the need for clinical trials to prevent accelerated atherosclerosis in SLE.
Abstract 1230 Correlation of Volumetric Magnetization Imaging (MTI) with Neuropsychological Functioning in Neuropsychiatric SLE
M.J. Rood, GPTh Bosma, N van Nierop, E LEM Bollen, FC Breedveld, H AM Middelkoop, T WJ Huizinga, MA van Buchem Leiden, The Netherlands
Cognitive function problems are the most common manifestation of SLE, but have been the hardest to study, because of controversy of whether they reflect active SLE, prior damage, or co-morbidity due to prednisone or depression.
A new technique, volumetric MTI, has been used in multiple sclerosis, where it has been found to be more sensitive than conventional MRI in quantifying damage. In the study, the peak height of the MTI histogram correlated with global impairment (p=0.034), and the specific domains of intelligence and memory.
Editorial Comment: This study is a major advance because it shows that aggressive dysfunction correlates with the global lesion load. This or similar techniques might allow detection of patients who should be treated before they become symptomatic.