Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial - 2010
Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial
Ginzler, Ellen M; Wofsy, David; Isenberg, Davidet al.
2010 • In Arthritis and Rheumatism, 62 (1), p. 211-221
[en] OBJECTIVE: To assess the effect of mycophenolate mofetil compared with
intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus
nephritis. METHODS: Patients with active lupus nephritis (renal biopsy class III,
IV, or V) were recruited for the study (n = 370) and treated with mycophenolate
mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5-1.0
gm/m(2)/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were
determined using measures of whole body disease activity, including the British
Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of
Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic
variables. RESULTS: Both treatments were effective on whole body disease activity
in the systems examined, as indicated by changes in the classic BILAG index. With
either treatment, remission was induced, notably in the mucocutaneous,
musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares
were rare, as measured by the SELENA-SLEDAI. Levels of complement C3, C4, and
CH50 and titers of anti-double-stranded DNA antibodies were normalized after
treatment with either mycophenolate mofetil or intravenous cyclophosphamide.
CONCLUSION: In addition to the efficacy of both treatments on the renal system,
this analysis showed that remission could also be induced in other systems. There
was no clear difference in efficacy between mycophenolate mofetil and intravenous
cyclophosphamide in ameliorating either the renal or nonrenal manifestations.
Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide
for the treatment of renal and nonrenal disease manifestations in patients with
biopsy-proven lupus nephritis.
Disciplines :
Rhumatologie
Auteur, co-auteur :
Ginzler, Ellen M
Wofsy, David
Isenberg, David
Gordon, Caroline
Lisk, Laura
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
Dooley, Mary-Anne
Langue du document :
Anglais
Titre :
Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial
Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005;353:2219-28.
Grootscholten C, Bajema IM, Florquin S, Steenbergen EJ, Peutz-Kootstra CJ, Goldschmeding R, et al. Treatment with cyclophosphamide delays the progression of chronic lesions more effectively than does treatment with azathioprine plus methylprednisolone in patients with proliferative lupus nephritis. Arthritis Rheum 2007;56:924-37.
Bezerra EL, Vilar MJ, da Trindade Neto PB, Sato EI. Doubleblind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus. Arthritis Rheum 2005;52:3073-8.
Ng KP, Cambridge G, Leandro MJ, Edwards JC, Ehrenstein M, Isenberg DA. B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of response. Ann Rheum Dis 2007;66:1259-62.
Gordon C, Wallace DJ, Shinada S, Kalunian KC, Forbess L, Braunstein GD, et al. Testosterone patches in the management of patients with mild/moderate systemic lupus erythematosus. Rheumatology (Oxford) 2008;47:334-8.
Griffiths B, Emery P, Isenberg D, Akil M, Thompson R, Maddison P, et al. The BILAG multi-centre RCT comparing cyclosporine (CyA) versus azathioprine (AZA) in patients with severe SLE: evaluation of disease activity, damage and quality of life [abstract]. Arthritis Rheum 2006;54 Suppl:S789.
Fortin PR, Abrahamowicz M, Ferland D, Lacaille D, Smith CD, Zummer M, et al, for the Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus. Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a doubleblind, randomized, placebo-controlled trial. Arthritis Rheum 2008;59:1796-804.
Tam LS, Li EK, Wong CK, Lam CW, Szeto CC. Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus. Lupus 2004;13:601-4.
Wang HY, Cui TG, Hou FF, Ni ZH, Chen XM, Lu FM, et al. Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study. Lupus 2008;17:638-44.
Tam LD, Li EK, Wong CK, Lam CW, Li WC, Szeto CC. Safety and efficacy of leflunomide in the treatment of lupus nephritis refractory or intolerant to traditional immunosuppressive therapy: an open-label trial. Ann Rheum Dis 2006;65:417-8.
Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Dehydroepiandosterone for systemic lupus erythematosus [abstract]. Cochrane Database Syst Rev 2007;17:CD005114. http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/ CD005114/pdf-fs.html.
Chatham W, Furie R, Petri M, Ginzler EM, Wallace DJ, Stohl W, et al, for the LBSL02/99 Study Group. Belimumab (fully human monoclonal antibody to BLyS) improved or stabilized systemic lupus erythematosus (SLE) disease activity over 3 years of therapy [abstract]. Arthritis Rheum 2008;58 Suppl:S573.
Wallace DJ, Lisse J, Stohl W, McKay J, Boling E, Merrill JT, et al. Belimumab (Bmab), a fully human monoclonal antibody to B-lymphocyte stimulator (Blys), shows bioactivity and reduces systemic lupus erythematosus disease activity. Proceedings of the Annual European Congress of Rheumatology (EULAR); 2006 June 21-24; Amsterdam, The Netherlands.
Furie R, Lisse J, Merrill JT, Petri M, Ginzler E, Aranow C, et al. Multiple SLE disease activity measures in a multi-center phase 2 SLE trial demonstrate belimumab (fully human monoclonal antibody to B-lymphocyte stimulator [Blys]) improves or stabilizes SLE activity. Proceedings of the Annual European Congress of Rheumatology (EULAR); 2006 June 21-24; Amsterdam, The Netherlands.
Mok CC. Mycophenolate mofetil for non-renal manifestations of systemic lupus erythematosus: a systematic review. Scand J Rheumatol 2007;36:329-37.
Pisoni CN, Sanchez FJ, Karim Y, Cuadrado MJ, D'Cruz DP, Abbs IC, et al. Mycophenolate mofetil in systemic lupus erythematosus: efficacy and tolerability in 86 patients. J Rheumatol 2005;32:1047-52.
Gordon C, Bertsias G, Ioannidis JP, Boletis J, Bombardieri S, Cervera R, et al. EULAR points to consider for conducting clinical trials in systemic lupus erythematosus. Ann Rheum Dis 2009;68:470-6.
Hay EM, Bacon PA, Gordon C, Isenberg DA, Maddison P, Snaith ML, et al. The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 1993;86:447-58.
Isenberg DA, Gordon C, for the British Isles Lupus Assessment Group. From BILAG to BLIPS: disease activity assessment in lupus past, present and future. Lupus 2000;9:651-4.
Sinclair A, Appel G, Dooley MA, Ginzler E, Isenberg D, Jayne D, et al. Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS). Lupus 2007;16:972-80.
Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne D, et al. Mycophenolate mofetil versus cyclophosphamide as lupus nephritis induction treatment: a randomized trial. J Am Soc Nephrol 2009;20:1103-12.
Hochberg MC, for the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725.
Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241-50.
Austin HA 3rd, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986;314:614-9.
Brunner HI, Feldman BM, Bombardier C, Silverman ED. Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index, British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus. Arthritis Rheum 1999;42:1354-60.
Ward MM, Marx AS, Barry NN. Comparison of the validity and sensitivity to change of 5 activity indices in systemic lupus erythematosus. J Rheumatol 2000;27:664-70.
Isenberg DA, Rahman A, Allen E, Farewell V, Akil M, Bruce IN, et al. BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford) 2005;44:902-6.
Yee CS, Farewell V, Isenberg DA, Prabu A, Sokoll K, Teh LS, et al. Revised British Isles Lupus Assessment Group 2004 index: a reliable tool for assessment of systemic lupus erythematosus activity. Arthritis Rheum 2006;54:3300-5.
Petri M, Buyon J, Kim M. Classification and definition of major flares in SLE clinical trials. Lupus 1999;8:685-91.
Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. Arthritis Rheum 1996;39:363-9.
Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C, et al. The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus. Arthritis Rheum 1997;40:809-13.
Alba P, Karim MY, Hunt BJ. Mycophenolate mofetil as a treatment for autoimmune haemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome. Lupus 2003;12:633-5.
Mak A, Mok CC. Mycophenolate mofetil for refractory haemolytic anemia in systemic lupus erythematosus. Lupus 2005;14:856-8.
Mok CC, Mak A, To CH. Mycophenolate mofetil for lupus related myelopathy. Ann Rheum Dis 2006;65:971-3.
