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

Authors

  • Ellen M. Ginzler,

    1. State University of New York Downstate Medical Center, Brooklyn
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    • Dr. Ginzler has served on a steering committee (unpaid) and received research funding from Aspreva/Vifor, and has received consulting fees, speaking fees, and/or honoraria from MedImmune, Wyeth, Cephalon, Genentech, Aspreva Pharmaceuticals, Bristol-Myers Squibb, Human Genome Sciences, Merck Serono, Teva Pharmaceuticals, and Zymogenetics (less than $10,000 each), and from the investment analysts Guidepoint Global and Gerson Lehman Group.

  • David Wofsy,

    1. University of California, San Francisco
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    • Dr. Wofsy has received consulting fees and/or honoraria from Genentech, Bristol-Myers Squibb, Merck Serono, Teva Pharmaceuticals, and Anthera Pharmaceuticals.

  • David Isenberg,

    1. University College London, London, UK
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  • Caroline Gordon,

    1. University of Birmingham and University Hospital Birmingham National Health Service Foundation Trust, Birmingham, UK
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    • Dr. Gordon has received consulting fees and an educational grant from Aspreva Pharmaceuticals and consulting fees from Bristol-Myers Squibb, Roche, and UCB (more than $10,000 each), and consulting fees from Amgen (less than $10,000).

  • Laura Lisk,

    Corresponding author
    1. Vifor Pharma Ltd. (formerly, Aspreva Pharmaceuticals), Bagshot, Surrey, UK
    • The Old Stables, Bagshot Park, Bagshot, Surrey GU19 5PJ, UK
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  • Mary-Anne Dooley

    1. University of North Carolina, Chapel Hill
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  • ClinicalTrials.gov identifier: NCT00377637. This is protocol WX17801 from the Aspreva Lupus Management Study Group (see Appendix A for principal investigators and study centers).

Abstract

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/m2/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.

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