Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS)

Sinclair, Andrew; Appel, Gerald B.; Dooley, Mary Anne; Ginzler, Ellen M.; Isenberg, David; Jayne, David; Wofsy, David; Solomons, Neil

doi:10.1177/0961203307084712

Cited by 97 publications

(72 citation statements)

References 48 publications

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“…NCT00377637) has been published. 32 The study was conducted in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice. The institutional review boards at all participating centers approved the protocol, and all patients provided written informed consent.…”

Section: Design Overviewmentioning

confidence: 99%

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Appel¹,

Contreras²,

Dooley³

et al. 2009

Journal of the American Society of Nephrology

951

761

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Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m 2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

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Section: Design Overviewmentioning

confidence: 99%

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Appel¹,

Contreras²,

Dooley³

et al. 2009

Journal of the American Society of Nephrology

951

761

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“…Results of the induction study and detailed descriptions of methods for both phases have been reported previously. 13,18 The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice principles. The institutional review boards at the participating centers approved the protocol, and all patients or their representatives provided written informed consent.…”

Section: Study Design and Oversightmentioning

confidence: 99%

Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis

et al. 2011

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BACKGROUND: Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus nephritis. METHODS: We carried out a 36-month, randomized, double-blind, double-dummy, phase 3 study comparing oral mycophenolate mofetil (2 g per day) and oral azathioprine (2 mg per kilogram of body weight per day), plus placebo in each group, in patients who met response criteria during a 6-month induction trial. The study group underwent repeat randomization in a 1:1 ratio. Up to 10 mg of prednisone per day or its equivalent was permitted. The primary efficacy end point was the time to treatment failure, which was defined as death, end-stage renal disease, doubling of the serum creatinine level, renal flare, or rescue therapy for lupus nephritis. Secondary assessments included the time to the individual components of treatment failure and adverse events. RESULTS: A total of 227 patients were randomly assigne...

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“…ALMS is an international trial of 370 patients with class III-V lupus nephritis comparing pulse monthly intravenous (IV) cyclophosphamide (CYC) to mycophenolate mofetil (MMF) for the induction of renal response (2,3). The data from this trial provided a rare opportunity to analyze a large population of prospectively followed, well-characterized, ethnically diverse lupus nephritis patients who were treated with two commonly used immunosuppressive agents.…”

Section: Introductionmentioning

confidence: 99%

Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide

Dall’Era¹,

Stone²,

Levesque³

et al. 2011

Arthritis Care & Research

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Objective. There is a need to identify clinical characteristics and/or biomarkers that can predict treatment outcome in lupus nephritis. To this end, we utilized data from the Aspreva Lupus Management Study to identify possible baseline and early predictors of renal response to mycophenolate mofetil (MMF) or intravenous (IV) cyclophosphamide (CYC). Methods. Patients with class III-V lupus nephritis were randomized to MMF or IV CYC. We assessed predictors of renal response, including baseline demographic, clinical, laboratory, and histologic characteristics, as well as early clinical and laboratory data, obtained within the first 2 months of therapy. Odds ratios (ORs) and 95% confidence intervals for renal response were calculated for each putative predictor. Results. Normalization of C3, C4, or both by week 8 was strongly predictive of renal response at week 24 (ORs 2.5, 2.6, and 2.9, respectively; P < 0.05). Reduction in proteinuria by >25% by week 8 was predictive of renal response at week 24 (OR 3.2, P < 0.05). Reduction in anti-double-stranded DNA (anti-dsDNA) by week 8 was not predictive of renal response. Only 3 baseline characteristics (C4 level, time since diagnosis of lupus nephritis, and estimated glomerular filtration rate [GFR]) were predictive of renal response; the remaining characteristics (age, age at lupus nephritis onset, time since diagnosis of systemic lupus erythematosus, sex, histopathologic class, anti-dsDNA antibody level, C3 level, level of proteinuria, and use of angiotensin-converting enzyme inhibitors, statins, or hydroxychloroquine) were not. Conclusion. This study demonstrates that baseline C4 level, time since diagnosis of lupus nephritis, baseline estimated GFR, early normalization of complement, and reduction in proteinuria independently predict renal response to therapy at 6 months.

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Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS)

Cited by 97 publications

References 48 publications

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis

Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide

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