The selective estrogen receptor α agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: A phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine

Arthritis and Rheumatism

Volumn 62, Issue 2, 2010, Pages 351-358

  Van Vollenhoven, Ronald F ^a   Houbiers, Jos G A ^b   Buttgereit, Frank ^c   Hout, Joanna In't ^b   Boers, Maarten ^d   Leij, Susanne ^b   Kvien, Tore K ^e   Dijkmans, Ben A C ^d   Szczepánski, Leszek ^f   Szombati, Istvan ^g   Sierakowski, Stanislaw ^h   Miltenburg, André M M ^b  

^a KAROLINSKA INSTITUTE   (Sweden)

^b Clinical Development Department   (Netherlands)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^e DIAKONHJEMMET HOSPITAL   (Norway)

^f Wydzia Fizjoterapii Wyzszej Szko y Spo eczno Przyrodniczej im W Pola   (Poland)

^g Diagnostics Unit Hungary   (Hungary)

^h MEDICAL UNIVERSITY OF BIALYSTOK   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

ESTROGEN; METHOTREXATE; ORG 37663; PLACEBO; SALAZOSULFAPYRIDINE; SELECTIVE ESTROGEN RECEPTOR ALPHA AGONIST; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SEX HORMONE BINDING GLOBULIN; UNCLASSIFIED DRUG;

ARTICLE; BACKACHE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE ACTIVITY; DOUBLE BLIND PROCEDURE; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; GASTROINTESTINAL SYMPTOM; HORMONE BLOOD LEVEL; HUMAN; HYPERCHOLESTEROLEMIA; MULTICENTER STUDY; NAUSEA; PERIPHERAL EDEMA; PHARYNGITIS; PHASE 2 CLINICAL TRIAL; POSTMENOPAUSE; PRIORITY JOURNAL; PROTEIN FUNCTION; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; TREATMENT RESPONSE; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION;

ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; DRUG THERAPY, COMBINATION; ESTROGEN RECEPTOR ALPHA; FEMALE; HUMANS; MEDICATION ADHERENCE; METHOTREXATE; MIDDLE AGED; PLACEBOS; POSTMENOPAUSE; STEROIDS; SULFASALAZINE; TREATMENT FAILURE;

EID: 75749152628     PISSN: 00043591     EISSN: 15290131     Source Type: Journal    
DOI: 10.1002/art.27196     Document Type: Article

References (29)

1. Harris ED Jr. Rheumatoid arthritis: pathophysiology and implications for therapy [review]. N Engl J Med 1990;322:1277-89.
2. Schuurs AH, Verheul HA. Effects of gender and sex steroids on the immune response [review]. J Steroid Biochem 1990;35:157-72.
3. Tengstrand B, Carlstroem K, Hafstroem I. Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism. Rheumatology (Oxford) 2002;41:285-9.
4. Wilder RL. Adrenal and gonadal steroid hormone deficiency in the pathogenesis of rheumatoid arthritis. J Rheumatol Suppl 1996;44:10-2.
5. Latman NS. Relation of menstrual cycle phase to symptoms of rheumatoid arthritis. Am J Med 1983;74:957-60.
6. Ostensen M, Aune B, Husby G. Effect of pregnancy and hormonal changes on the activity of rheumatoid arthritis. Scand J Rheumatol 1983;12:69-72.
7. Goemaere S, Ackerman C, Goethals K, De Keyser F, Van der Straeten C, Verbruggen G, et al. Onset of symptoms of rheumatoid arthritis in relation to age, sex and menopausal transition. J Rheumatol 1990;17:1620-2.
8. Vandenbroucke JP, Valkenburg HA, Boersma JW, Cats A, Festen JJ, Huber-Bruning O, et al. Oral contraceptives and rheumatoid arthritis: further evidence for a preventive effect. Lancet 1982;2: 839-42.
9. Romieu I, Hernandez-Avila M, Liang MH. Oral contraceptives and the risk of rheumatoid arthritis: a meta-analysis of a conflicting literature. Br J Rheumatol 1989;28 Suppl 1:13-7.
10. Bijlsma JW, Huber-Bruning O, Thijssen JH. Effect of oestrogen treatment on clinical and laboratory manifestations of rheumatoid arthritis. Ann Rheum Dis 1987;46:777-9.
11. D'Elia HF, Larsen A, Mattsson LA, Waltbrand E, Kvist G, Mellstrom D, et al. Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis. J Rheumatol 2003;30:1456-63.
12. Hall GM, Daniels M, Huskisson EC, Spector TD. A randomized controlled trial of the effect of hormone replacement therapy on disease activity in postmenopausal rheumatoid arthritis. Ann Rheum Dis 1994;53:112-6.
13. MacDonald A, Murphy E, Capell H, Bankowska U, Ralston S. Effects of hormone replacement therapy in rheumatoid arthritis: a double blind placebo-controlled study. Ann Rheum Dis 1994;53:54-7.
14. Van den Brink HR, van Everdingen AA, van Wijk MJ, Jacobs JW, Bijlsma JW. Adjuvant oestrogen therapy does not improve disease activity in postmenopausal patients with rheumatoid arthritis. Ann Rheum Dis 1993;52:862-5.
15. Walitt B, Pettinger M, Weinstein A, Katz J, Torner J, Wasko MC, et al, for the Women's Health Initiative Investigators. Effects of postmenopausal hormone therapy on rheumatoid arthritis: the Women's Health Initiative randomized controlled trials. Arthritis Rheum 2008;59:302-10.
16. Salem ML. Estrogen, a double-edged sword: modulation of Th1-and Th2-mediated inflammations by differential regulation of Th1/Th2 cytokine production [review]. Curr Drug Targets Inflamm Allergy 2004;3:97-104.
17. Miltenburg AM, van Laar JM, de Kuiper P, Daha MR, Breedveld FC. T cells cloned from human rheumatoid synovial membrane functionally represent the Th1 subset. Scand J Immunol 1992;35:603-10.
18. Dolhain RJ, van der Heiden AN, ter Haar NT, Breedveld FC, Miltenburg AM. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis Rheum 1996;39:1961-9.
19. Dulos J, Hofstra CL, Joosten LA, Veening-Griffioen DH, Lucassen MA, van Doorn CM, et al. A selective estrogen receptor α agonist (Org 37663) suppresses inflammation and arthritis in mouse models [abstract]. Ann Rheum Dis 2006;65 Suppl II:128.
20. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
21. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44-8.
22. Van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis: comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism criteria. Arthritis Rheum 1996;39:34-40.
23. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35.
24. Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 1993;36:729-40.
25. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum 1980;23:137-45.
26. Mansson B, Carey D, Alini M, Ionescu M, Rosenberg LC, Poole AR, et al. Cartilage and bone metabolism in rheumatoid arthritis: differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism. J Clin Invest 1995;95:1071-7.
27. Garnero P, Landewe R, Boers M, Verhoeven A, van der Linden S, Christgau S, et al. Association of baseline levels of markers of bone and cartilage degradation with long-term progression of joint damage in patients with early rheumatoid arthritis: the COBRA study. Arthritis Rheum 2002;46:2847-56.
28. Harris HA, Albert LM, Leathurby Y, Malamas MS, Mewshaw RE, Miller CP, et al. Evaluation of an estrogen receptor-β agonist in animal models of human disease. Endocrinology 2003;144:4241-9.
29. Harris HA. Estrogen receptor-β: recent lessons from in vivo studies [review]. Mol Endocrinol 2007;21:1-13.