Bromocriptine in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled study

Abstract

The objective of this study was to investigate the efficacy and safety of bromocriptine (BRC) as an adjunct to conventional treatment in systemic lupus erythematosus (SLE). A prospective, double-blind, randomized, placebo-controlled study compared BRC at a fixed daily dosage of 2.5 mg with placebo. Patients were followed for 2-17 months (mean 12.5 months). Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), numbers of flares were recorded, and serum prolactin (PRL) levels were obtained at intervals during the study. Patients were allowed to take prednisone and immunosuppressive drugs. Sixty-six patients with SLE entered the study. Thirty-six were treated with BRC, and 30 controls received placebo. Sixteen patients were removed from the study during the treatment period: five in each group left the study because of adverse effects, five became pregnant, and one patient who took placebo died with central nervous system lupus. Four patients in the BRC treatment group and three patients in the placebo group moved away or stopped coming for study visits for unknown reasons, and were lost to follow-up during the course. At entry, serum PRL was (mean+/-s.d.) 24.8 ng/ml+/-18.4 in the BRC treatment group. This value fell to 5.8+/-9.0 after 12 months of treatment. Corresponding PRL values in controls were 23.7+/-22.1 pretreatment and 20.3+/-14 after 12 months. PRL levels in BRC-treated subjects were significantly lower than levels in control subjects after 3, 6, 9, and 12 months of treatment. The SLEDAI score on the fifth protocol visit was decreased significantly in the BRC group vs controls: 0.9+/-1.4 vs 2.6+/-4.5 (P < 0.05). Although the absolute number of flares in each group was similar, the mean number of flares/patient/month was decreased significantly in the BRC group compared to the control group (0.08+/-0.1 vs 0.18+/-0.2, P = 0.03). Long term treatment with a low dose of BRC appears to be a safe and effective means of decreasing SLE flares in SLE patients.

Prolactin Is Not Required for the Development of Severe Chronic Experimental Autoimmune Encephalomyelitis

“…In mouse models of systemic lupus erythematosus (SLE), a multiorgan Ab-dependent autoimmune disease, PRL administration increases autoreactive immune responses (17,18), by breaking B cell tolerance and enhancing titers of autoreactive Abs (18). In human SLE, higher serum levels of PRL correlate with greater disease severity, and treatment of SLE patients with bromocriptine (BCR), a dopamine D2 agonist that inhibits PRL secretion, reduces disease activity (19).…”

Sex hormones and systemic lupus erythematosus: Review and meta‐analysis

“…This Ͼ7-fold difference is also markedly higher than the 1-2% prevalence of hyperprolactinemia reported for general populations (69,88) and was statistically significant compared with healthy controls (Mantel-Haenzel odds ratio). Prolactin probably stimulates lupus disease activity (89); serum prolactin and disease activity have been positively associated (71,87,90,91); abnormally high prolactin levels during pregnancy in SLE also correlate with disease activity (58,92); and 2 double-blind, placebocontrolled human studies have shown that suppression of prolactin with bromocriptine reduces SLE disease activity (93,94). Interestingly, bromocriptine not only suppresses prolactin but appears to increase estradiol concentrations (95) through increased aromatization of testosterone (96), implying a complex interaction for these hormones in lupus and its disease activity.…”

Human Prolactin Promotes Human Secondary Immunoglobulin Response in Human/SCID Mouse Chimeras

“…It has also been demonstrated that both nonstimulated and mitogen-stimulated lymphocytes from patients with lupus secrete more prolactin than do control lymphocytes (9,12). Bromocriptine, a drug that blocks prolactin secretion by the anterior pituitary gland, was suggested to have a beneficial effect in patients with SLE in small clinical trials (3,15). In order to study survival and activation of different populations of autoreactive B cells and the effects of prolactin on B cells, particularly anti-DNA production in SLE, an R4A-␥2b mouse model was established and well characterized (24,28).…”