Effectiveness of Mycophenolate Mofetil Combined With Tacrolimus for Steroid Tapering in Systemic Lupus Erythematosus

Summary

The goal of this clinical trial is to determine whether mycophenolate mofetil(MMF) combined with tacrolimus(TAC) can maintain remission in patients with lupus nephritis (LN) who have reached treatment targets after steroid tapering. The main question\[s\] it aims to answer are: * The efficacy, safety and tolerability of MMF combined with TAC regimen in the treatment of LN patients in the maintenance period. * The influence of low-dose steroid on carotid intima thickness (CIMT). * The omics and cell-free RNA (cfRNA) spectral differences related to lupus flare. * The differences in health economics between steroid tapering and steroid maintenance patients. Participants will be randomly assigned into 2 groups. In the steroid tapering group, participants will take MMF+TAC treatment without steroid for 1 year, and participants who stop steroid treatment without lupus flare will be randomly assigned to monotherapy with MMF or TAC. In the steroid maintenance group, participants will take MMF+TAC+steroid for 1 year, and participants without lupus flare will stop the use of steroid for 6 months. Participants without lupus flare after the stop of steroid will be randomly assigned to monotherapy with MMF or TAC.

Timeline

Start

2023-07-01

Primary completion

2025-07-31

Completion

2026-07-31

Publications

• Background Murimi-Worstell IB, Lin DH, Nab H, Kan HJ, Onasanya O, Tierce JC, Wang X, Desta B, Alexander GC, Hammond ER. Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis. BMJ Open. 2020 May 21;10(5):e031850. doi: 10.1136/bmjopen-2019-031850.
• Background Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. 2000 Aug;43(8):1801-8. doi: 10.1002/1529-0131(200008)43:83.0.CO;2-O.
• Background Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, Cervera R, Doria A, Gordon C, Govoni M, Houssiau F, Jayne D, Kouloumas M, Kuhn A, Larsen JL, Lerstrom K, Moroni G, Mosca M, Schneider M, Smolen JS, Svenungsson E, Tesar V, Tincani A, Troldborg A, van Vollenhoven R, Wenzel J, Bertsias G, Boumpas DT. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019 Jun;78(6):736-745. doi: 10.1136/annrheumdis-2019-215089. Epub 2019 Mar 29.
• Background Tani C, Elefante E, Signorini V, Zucchi D, Lorenzoni V, Carli L, Stagnaro C, Ferro F, Mosca M. Glucocorticoid withdrawal in systemic lupus erythematosus: are remission and low disease activity reliable starting points for stopping treatment? A real-life experience. RMD Open. 2019 Jun 11;5(2):e000916. doi: 10.1136/rmdopen-2019-000916. eCollection 2019.
• Background Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hie M, Pineton de Chambrun M, Boutin THD, Miyara M, Gorochov G, Yssel H, Cherin P, Devilliers H, Amoura Z. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial. Ann Rheum Dis. 2020 Mar;79(3):339-346. doi: 10.1136/annrheumdis-2019-216303. Epub 2019 Dec 18.
• Background Villarroel MC, Hidalgo M, Jimeno A. Mycophenolate mofetil: An update. Drugs Today (Barc). 2009 Jul;45(7):521-32. doi: 10.1358/dot.2009.45.7.1384878.
• Background Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I, Boletis J, Frangou E, Houssiau FA, Hollis J, Karras A, Marchiori F, Marks SD, Moroni G, Mosca M, Parodis I, Praga M, Schneider M, Smolen JS, Tesar V, Trachana M, van Vollenhoven RF, Voskuyl AE, Teng YKO, van Leew B, Bertsias G, Jayne D, Boumpas DT. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020 Jun;79(6):713-723. doi: 10.1136/annrheumdis-2020-216924. Epub 2020 Mar 27.
• Background Mok CC. Mycophenolate mofetil for non-renal manifestations of systemic lupus erythematosus: a systematic review. Scand J Rheumatol. 2007 Sep-Oct;36(5):329-37. doi: 10.1080/03009740701607042.
• Background Broen JCA, van Laar JM. Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):167-178. doi: 10.1038/s41584-020-0374-8. Epub 2020 Feb 13.
• Background Yoon KH. Efficacy and cytokine modulating effects of tacrolimus in systemic lupus erythematosus: a review. J Biomed Biotechnol. 2010;2010:686480. doi: 10.1155/2010/686480. Epub 2010 Jun 28.
• Background Hannah J, Casian A, D'Cruz D. Tacrolimus use in lupus nephritis: A systematic review and meta-analysis. Autoimmun Rev. 2016 Jan;15(1):93-101. doi: 10.1016/j.autrev.2015.09.006. Epub 2015 Sep 30.
• Background Zhang H, Liu Z, Zhou M, Liu Z, Chen J, Xing C, Lin H, Ni Z, Fu P, Liu F, Chen N, He Y, Liu J, Zeng C, Liu Z. Multitarget Therapy for Maintenance Treatment of Lupus Nephritis. J Am Soc Nephrol. 2017 Dec;28(12):3671-3678. doi: 10.1681/ASN.2017030263. Epub 2017 Jul 31.
• Background Peng L, Wang Z, Li M, Wang Y, Xu D, Wang Q, Zhang S, Zhao J, Tian X, Zeng X. Flares in Chinese systemic lupus erythematosus patients: a 6-year follow-up study. Clin Rheumatol. 2017 Dec;36(12):2727-2732. doi: 10.1007/s10067-017-3842-z. Epub 2017 Sep 19.

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Indications