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Current Rheumatology Reviews

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ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

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Clinical Trial

Efficacy of Raloxifene as Add-on Therapy on Disease Activity of Postmenopausal Women with Rheumatoid Arthritis: A Double-blind, Randomized, Placebo-controlled Clinical Trial

Author(s): Maryam Sahebari, Maryam Sarafraz Yazdi, Seyedeh Mehrnaz Aghili, Habibollah Esmaily, Sara Saeidi and Masoumeh Salari*

Volume 19, Issue 1, 2023

Published on: 21 July, 2022

Page: [93 - 101] Pages: 9

DOI: 10.2174/1573397118666220518114415

Price: $65

Abstract

Objective: The current study aimed to evaluate the effect of raloxifene on the disease activity of postmenopausal patients with rheumatoid arthritis (RA) and the prevention of glucocorticoid- induced osteoporosis.

Methods: This double-blind, randomized clinical trial was conducted at the Rheumatic Diseases Research Center affiliated with Mashhad University of Medical Sciences from 2015 to 2016. Postmenopausal women with RA were randomly treated with raloxifene or placebo after discontinuation of alendronate. Disease activity was evaluated using DAS28ESR, HAQ, and VAS before and every two months after the intervention. In addition, bone mineral densitometry was performed for patients before and 14 months after the intervention. The disease activity and densitometric criteria were compared between the two groups at a significant level of p <0.05.

Results: A total of 17 patients were allocated to each group. The two groups were similar at baseline in underlying disease, age, duration of RA, duration of alendronate use, laboratory findings, and rheumatoid arthritis drugs. Moreover, the mean scores of DAS28ESR, HAQ, and VAS during visits were not significantly different between the intervention and control groups (p >0.05).

Conclusion: The current study results could not prove any clinical benefits of adding raloxifene to standard therapies for patients with rheumatoid arthritis in improving their disease activity compared to placebo.

Clinical Trial Registration Number: Trial registration number is NCT02982083

Keywords: Rheumatoid arthritis, raloxifene, disease activity, osteoporosis, DAS28ESR, T-immune cells.

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[1]
Safiri S, Kolahi AA, Hoy D, et al. Global, regional and national burden of rheumatoid arthritis 1990-2017: A systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis 2019; 78(11): 1463-71.
[http://dx.doi.org/10.1136/annrheumdis-2019-215920] [PMID: 31511227]
[2]
Islander U, Jochems C, Lagerquist MK, Forsblad-d’Elia H, Carlsten H. Estrogens in rheumatoid arthritis; the immune system and bone. Mol Cell Endocrinol 2011; 335(1): 14-29.
[http://dx.doi.org/10.1016/j.mce.2010.05.018] [PMID: 20685609]
[3]
Islander U, Jochems C, Stubelius A, et al. Combined treatment with dexamethasone and raloxifene totally abrogates osteoporosis and joint destruction in experimental postmenopausal arthritis. Arthritis Res Ther 2011; 13(3): R96.
[http://dx.doi.org/10.1186/ar3371] [PMID: 21689408]
[4]
Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020; 79(6): 685-99.
[http://dx.doi.org/10.1136/annrheumdis-2019-216655] [PMID: 31969328]
[5]
Lucas CJ, Dimmitt SB, Martin JH. Optimising low-dose methotrexate for rheumatoid arthritis-A review. Br J Clin Pharmacol 2019; 85(10): 2228-34.
[http://dx.doi.org/10.1111/bcp.14057] [PMID: 31276602]
[6]
Lim SS, Conn DL. The use of low-dose prednisone in the management of rheumatoid arthritis. Bull Rheum Dis 2001; 50(12): 1-4.
[PMID: 12386945]
[7]
Jochems C, Lagerquist M, Håkansson C, Ohlsson C, Carlsten H. Long-term anti-arthritic and anti-osteoporotic effects of raloxifene in established experimental postmenopausal polyarthritis. Clin Exp Immunol 2008; 152(3): 593-7.
[http://dx.doi.org/10.1111/j.1365-2249.2008.03660.x] [PMID: 18435803]
[8]
Jochems C, Islander U, Kallkopf A, Lagerquist M, Ohlsson C, Carlsten H. Role of raloxifene as a potent inhibitor of experimental post-menopausal polyarthritis and osteoporosis. Arthritis Rheum 2007; 56(10): 3261-70.
[http://dx.doi.org/10.1002/art.22873] [PMID: 17907171]
[9]
Jansson L, Holmdahl R. Enhancement of collagen-induced arthritis in female mice by estrogen receptor blockage. Arthritis Rheum 2001; 44(9): 2168-75.
[http://dx.doi.org/10.1002/1529-0131(200109)44:9<2168::AID-ART370>3.0.CO;2-2] [PMID: 11592382]
[10]
Crandall CJ, Newberry SJ, Diamant A, et al. Comparative effectiveness of pharmacologic treatments to prevent fractures: An updated systematic review. Ann Intern Med 2014; 161(10): 711-23.
[http://dx.doi.org/10.7326/M14-0317] [PMID: 25199883]
[11]
Cranney A, Tugwell P, Zytaruk N, et al. Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Endocr Rev 2002; 23(4): 524-8.
[http://dx.doi.org/10.1210/er.2001-4002] [PMID: 12202467]
[12]
Nelson HD, Smith ME, Griffin JC, Fu R. Use of medications to reduce risk for primary breast cancer: A systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2013; 158(8): 604-14.
[http://dx.doi.org/10.7326/0003-4819-158-8-201304160-00005] [PMID: 23588749]
[13]
Riggs BL, Hartmann LC. Selective estrogen-receptor modulators - mechanisms of action and application to clinical practice. N Engl J Med 2003; 348(7): 618-29.
[http://dx.doi.org/10.1056/NEJMra022219] [PMID: 12584371]
[14]
Mokuda S, Okuda Y, Onishi M, et al. Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendronate or glucocorticoids have lower serum undercarboxylated osteocalcin levels. J Endocrinol Invest 2012; 35(7): 661-4.
[PMID: 21970822]
[15]
Chang K, Yang SM, Kim SH, Han KH, Park SJ, Shin JI. Smoking and rheumatoid arthritis. Int J Mol Sci 2014; 15(12): 22279-95.
[http://dx.doi.org/10.3390/ijms151222279] [PMID: 25479074]
[16]
Furst DE, Emery P. Rheumatoid arthritis pathophysiology: Update on emerging cytokine and cytokine-associated cell targets. Rheumatology (Oxford) 2014; 53(9): 1560-9.
[http://dx.doi.org/10.1093/rheumatology/ket414] [PMID: 24402580]
[17]
Wolfe F, Michaud K, Li T. Sleep disturbance in patients with rheumatoid arthritis: Evaluation by medical outcomes study and visual analog sleep scales. J Rheumatol 2006; 33(10): 1942-51.
[PMID: 16960928]
[18]
D’Elia HF, Larsen A, Mattsson L-A, et al. Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis. J Rheumatol 2003; 30(7): 1456-63.
[PMID: 12858441]
[19]
Hayward M, Fiedler-Nagy C. Mechanisms of bone loss: Rheumatoid arthritis, periodontal disease and osteoporosis. Agents Actions 1987; 22(3-4): 251-4.
[http://dx.doi.org/10.1007/BF02009053] [PMID: 3328495]
[20]
Holmdahl R, Carlsten H, Jansson L, Larsson P. Oestrogen is a potent immunomodulator of murine experimental rheumatoid disease. Br J Rheumatol 1989; 28 (Suppl. 1): 54-8.
[http://dx.doi.org/10.1093/rheumatology/XXVIII.suppl_1.54] [PMID: 2684319]
[21]
Goemaere S, Ackerman C, Goethals K, et al. Onset of symptoms of rheumatoid arthritis in relation to age, sex and menopausal transition. J Rheumatol 1990; 17(12): 1620-2.
[PMID: 2084234]
[22]
Yilmaz L, Özoran K, Gündüz OH, Uçan H, Yücel M. Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids. Rheumatol Int 2001; 20(2): 65-9.
[http://dx.doi.org/10.1007/s002960000080] [PMID: 11269535]
[23]
Hayashi I, Hagino H, Okano T, Enokida M, Teshima R. Effect of raloxifene on arthritis and bone mineral density in rats with collagen-induced arthritis. Calcif Tissue Int 2011; 88(2): 87-95.
[http://dx.doi.org/10.1007/s00223-010-9432-6] [PMID: 21140260]
[24]
Mok CC, Ying SK, Ma KM, Wong CK. Effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus: Subgroup analysis of a double-blind randomized controlled trial. Lupus 2013; 22(14): 1470-8.
[http://dx.doi.org/10.1177/0961203313507987] [PMID: 24113197]
[25]
Mok CC, To CH, Mak A, Ma KM. Raloxifene for postmenopausal women with systemic lupus erythematosus: A pilot randomized controlled study. Arthritis Rheum 2005; 52(12): 3997-4002.
[http://dx.doi.org/10.1002/art.21477] [PMID: 16320346]
[26]
Roman-Blas JA, Castañeda S, Cutolo M, Herrero-Beaumont G. Efficacy and safety of a selective estrogen receptor β agonist, ERB-041, in patients with rheumatoid arthritis: A 12-week, randomized, placebo-controlled, phase II study. Arthritis Care Res (Hoboken) 2010; 62(11): 1588-93.
[http://dx.doi.org/10.1002/acr.20275] [PMID: 20556817]
[27]
Lee W, Min I-S, Choi Y-J, Lee C-H, Lee M-S, Yoo W-H. SAT0497 effect of raloxifene on osteoporosis and disease activity in postmenopausal female with rheumatic diseases. Ann Rheum Dis 2014; 73 (Suppl. 2): 772.
[http://dx.doi.org/10.1136/annrheumdis-2014-eular.5035]
[28]
Stoica S, Zugravu G. THU0402 effects of raloxifene for prevention of bone loss in rheumatoid arthritis women receiving long-term glucocorticoids. Annals of the Rheumatic Disease 2013; 72 (Suppl. 3): A301.
[http://dx.doi.org/10.1136/annrheumdis-2013-eular.930]
[29]
Mok CC, Ying KY, To CH, et al. Raloxifene for prevention of glucocorticoid-induced bone loss: A 12-month randomised double-blinded placebo-controlled trial. Ann Rheum Dis 2011; 70(5): 778-84.
[http://dx.doi.org/10.1136/ard.2010.143453] [PMID: 21187295]
[30]
Dolan AL, Moniz C, Abraha H, Pitt P. Does active treatment of rheumatoid arthritis limit disease-associated bone loss? Rheumatology (Oxford) 2002; 41(9): 1047-51.
[http://dx.doi.org/10.1093/rheumatology/41.9.1047] [PMID: 12209040]

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