TY - JOUR
T1 - The Selective Estrogen Receptor alpha Agonist Org 37663 Induces Estrogenic Effects but Lacks Antirheumatic Activity
AU - van Vollenhoven, R.F.
AU - Houbiers, J.G.A.
AU - Buttgereit, F.
AU - in't Hout, J.
AU - Boers, M.
AU - Leij, S.
AU - Kvien, T.K.
AU - Dijkmans, B.A.C.
AU - Szczepanski, L.
AU - Szombati, I.
AU - Sierakowski, S.
AU - Miltenburg, A.M.M.
AU - Szczepański, Leszek
PY - 2010
Y1 - 2010
N2 - Objective. Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ER alpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. Methods. A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Results. Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. Conclusion. The observed lack of clinical benefit in RA patients treated with an ER alpha agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ER alpha mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs
AB - Objective. Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ER alpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. Methods. A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Results. Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. Conclusion. The observed lack of clinical benefit in RA patients treated with an ER alpha agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ER alpha mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs
U2 - https://doi.org/10.1002/art.27196
DO - https://doi.org/10.1002/art.27196
M3 - Article
C2 - 20112368
SN - 0004-3591
VL - 62
SP - 351
EP - 358
JO - Arthritis & Rheumatism
JF - Arthritis & Rheumatism
IS - 2
ER -