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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.
J Rheumatol 2008; 35(5):797JR

Abstract

OBJECTIVE

Estrogen plays a role in the activation of systemic lupus erythematosus (SLE) and in upregulating intracellular signals by binding to the estrogen receptor(s). Fulvestrant (Faslodex, AstraZeneca Pharmaceuticals, Wilmington, DE, USA), an estrogen selective receptor downregulator, competes for receptor binding in vitro and inhibits estrogen action in target cells. We evaluated the efficacy, side effects, and expression of T cell activation markers, following the administration of fulvestrant or placebo to premenopausal patients with SLE.

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.

Authors+Show Affiliations

From the Center for Rheumatic Disease, Allergy-Immunology, St. Luke's Hospital, University of Missouri, Kansas City, Missouri 64111, USA. niabdou@centerforrheumatic.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18381791

Citation

Abdou, Nabih I., et al. "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." The Journal of Rheumatology, vol. 35, no. 5, 2008, p. 797.
Abdou NI, Rider V, Greenwell C, et al. 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. J Rheumatol. 2008;35(5):797.
Abdou, N. I., Rider, V., Greenwell, C., Li, X., & Kimler, B. F. (2008). 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. The Journal of Rheumatology, 35(5), p. 797.
Abdou NI, et al. 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. J Rheumatol. 2008;35(5):797. PubMed PMID: 18381791.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Abdou,Nabih I, AU - Rider,Virginia, AU - Greenwell,Cindy, AU - Li,Xiaolan, AU - Kimler,Bruce F, Y1 - 2008/03/15/ PY - 2008/4/3/pubmed PY - 2008/8/22/medline PY - 2008/4/3/entrez SP - 797 EP - 797 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 35 IS - 5 N2 - OBJECTIVE: Estrogen plays a role in the activation of systemic lupus erythematosus (SLE) and in upregulating intracellular signals by binding to the estrogen receptor(s). Fulvestrant (Faslodex, AstraZeneca Pharmaceuticals, Wilmington, DE, USA), an estrogen selective receptor downregulator, competes for receptor binding in vitro and inhibits estrogen action in target cells. We evaluated the efficacy, side effects, and expression of T cell activation markers, following the administration of fulvestrant or placebo to premenopausal patients with SLE. 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. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/18381791/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_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&amp;pmid=18381791 DB - PRIME DP - Unbound Medicine ER -