Abstract
IntroductionThe aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares.MethodsAt inclusion, steady-state PK parameters of the MMF active form, mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) were determined for 25 stable SLE patients without renal manifestations. Disease activity was assessed during 6 months of follow-up. Potential relationships between those entry MMF-PK variables and clinical outcome were analyzed.ResultsMMF controlled disease activity in 17 patients (successes) and failed to do so for 8 others (failures). For failures and successes, respectively, entry MPA areas under the time-concentration curve between 0 and 12 hours (AUC0-12 h) (medians: 37.7 vs 73.1 mg/h/L, P = 0.003) and MPA 12-hour trough concentrations (C12 h) (medians: 1.5 vs 3.7 mg/L, P = 0.008) were significantly lower, and inclusion MPAG/MPA C12 h ratios (medians: 18.7 vs 10.2, P = 0.02) were significantly higher. According to our receiver operating characteristics curve analysis, MPA C12 h was best able to discriminate a flare during follow-up (93% sensitivity, 85% specificity). A 3-mg/L cut-off had 92% negative-predictive value for developing a flare during follow-up.ConclusionsFor our SLE patients without renal manifestations, clinical flares developing under maintenance therapy were associated with steady-state inclusion MPA C12 h < 3 mg/L.
Highlights
The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares
A positive correlation was observed between MMF dose and mycophenolic acid (MPA) AUC0-12 h (r = 0.58, P = 0.01) or MPA C12 h (r = 0.53, P = 0.02)
Receiver operating characteristic curve analysis AUC ROCs were 0.86, 0.89, and 0.75, respectively, for MPA AUC0-12 h, MPA C12 h, and mycophenolic acid glucuronide (MPAG)/ MPA C12 h ratio
Summary
The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares. Systemic lupus erythematosus (SLE) is a chronic remitting-and-relapsing disease that engenders considerable health-care costs for each patient and may require longterm treatment with immunosuppressive agents [1]. Mycophenolate mofetil (MMF), an immunosuppressant widely used to prevent solid organ transplant rejection [2], is being used increasingly to induce SLE remission of minor relapses and to maintain remission after induction therapy [1]. The dose used to control SLE activity usually ranges from 1.5 to 3 g daily and is based largely on clinical experience, which is very limited. Most patients experience periodic disease flares, so maintaining disease control remains a challenge. The lupus flare rate varies among studies, often because of the different populations studied [1]
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