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Fulvestrant (Faslodex), an Estrogen Selective Receptor Downregulator, in Therapy of Women with Systemic Lupus Erythematosus. Clinical, Serologic, Bone Density, and T Cell Activation Marker Studies: A Double-blind Placebo-controlled Trial NABIH I. ABDOU, VIRGINIA RIDER, CINDY GREENWELL, XIAOLAN LI, and BRUCE F. KIMLER
ABSTRACT. Methods. Twenty women with moderate SLE Disease Activity Index (SLEDAI; 7.87 ± 3.7) were enrolled. They were premenopausal with regular menstrual cycles and not taking exogenous hormones. The study was double-blind and placebo-controlled. Ten patients received 250 mg fulvestrant intramuscularly for 12 months, and 10 received the placebo. All were observed monthly and 3 months after final fulvestrant/placebo injection. Measures studied were monthly SLEDAI scores, routine and serologic markers for lupus, and serum concentrations of estrogen and fulvestrant. Expression of T cell calcineurin and CD154 mRNA in peripheral T cells was measured by polymerase chain reaction. Medications the patients were taking were recorded each visit. Bone density was obtained at baseline and at visit 12. Results. Sixteen patients completed the 15-month study, 8 from each group. SLEDAI improved significantly in the fulvestrant group at both 12 months (p = 0.02) and 15 months (p = 0.002), but serologic markers, routine laboratory tests, and bone density did not. Serum estrogen levels were higher in the fulvestrant group and dropped when fulvestrant was discontinued; these differences were not statistically significant. Medications for therapy of lupus to the fulvestrant group were reduced, whereas the placebo group medications were unchanged or increased. Comparison of relative values at individual timepoints revealed significantly lower median values for the T cell activation markers CD154 (p < 0.001) and calcineurin (p = 0.013) in the fulvestrant arm. Conclusion. Blocking estrogen receptors in vivo by an estrogen selective receptor downregulator could be considered as a new and relatively safe therapeutic approach in the management of SLE patients with moderately active disease for the 1-year study period. (First Release Mar 15 2008; J Rheumatol 2008;35:797-803) Key Indexing Terms:
SYSTEMIC LUPUS ERYTHEMATOSUS
From the Center for Rheumatic Disease, Allergy-Immunology, St. Luke's Hospital, University of Missouri, Kansas City, Missouri; Department of Biology, Pittsburg State University, Pittsburg, Kansas; and Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas, USA. Supported by AstraZeneca Pharmaceutical Company (study IRUSFULV0031) and by NIH grant A149272 and RR-16475 from the INBRE program of the National Center for Research Services, Evans Memorial Funds, Saint Luke's Hospital Foundation Research Funds, and by private funds from the Center for Rheumatic Diseases. N.I. Abdou, MD, PhD, Clinical Professor of Medicine; C. Greenwell, RN, Research Coordinator, Center for Rheumatic Disease, Allergy-Immunology, St. Luke's Hospital; V. Rider, PhD, Professor of Biology, Pittsburg State University; X. Li, MD, Visiting Scholar, Department of Biology, Pittsburg State University, Kunming Medical College, Kunming, People's Republic of China; B.F. Kimler, PhD, Professor of Radiation Oncology, University of Kansas Medical Center. Address reprint requests to Dr. N.I. Abdou, Center for Rheumatic Disease, St. Luke's Hospital, 4330 Wornall Road, Suite 40-II, Kansas City, MO 64111. E-mail: niabdou@centerforrheumatic.com Accepted for publication December 20, 2007. |
