Lower 12-hour Trough Concentrations of Mycophenolic Acid in Patients with Active Systemic Vasculitides Taking Mycophenolate Mofetil

Djabarouti, Sarah; Lazaro, Estibaliz; Breilh, Dominique; Pellegrin, Jean‐Luc; Viallard, Jean‐François

doi:10.3899/jrheum.120606

Cited by 2 publications

(4 citation statements)

References 11 publications

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“…Our study, conducted on new patient groups, confirmed our previously published findings for autoimmune diseases : associations between C 0 < 3 mg l –1 (SLE) and <2.5 mg l –1 (vasculitis) and clinical flares. A strong correlation was observed between MPA AUC(0,12 h) and C 0 measured on average 12.7 h after MMF administration, suggesting that, should the benefit of TDM be further confirmed, it can be based on pre‐dose concentration monitoring .…”

Section: Discussionsupporting

confidence: 90%

“…We previously investigated MPA PK in autoimmune diseases patients and observed that clinical flares were significantly associated with MPA C12h ≤3 mg l -1 for those with SLE and 2.5 mg l -1 for those with vasculitis [18,21]. The primary objective of this study was to confirm those previously established target thresholds and the optimal PK parameter to monitor, in a group of new patients followed in our department between 2009 and 2013.…”

Section: Introductionmentioning

confidence: 72%

“…Clinical outcomes of patients in remission at PK assessment were evaluated over 12 months with respect to their plasma MPA concentrations, i.e. lower or higher than plasma concentrations of efficacy previously published ( C 12 h = 3 mg l −1 for patients with SLE and C 12 h = 2.5 mg l −1 for those with vasculitis). Clinical outcomes of patients experiencing a flare at PK evaluation and whose MMF doses were increased were assessed over 6 months after dose adjustment.…”

Section: Methodsmentioning

confidence: 99%

“…MMF is also used to treat anti‐neutrophil cytoplasm antibodies‐associated vasculitis and polyarteritis nodosa, although its efficacy seems to be lower than that of azathioprine . However, according to some authors, interindividual MPA PK variability is wide and clinical vasculitis flares were significantly associated with MPA C 12 h ≤2.5 mg l –1 . Therapeutic optimization based on MPA TDM is challenging in patient management, and to date, a target concentration C 12 h = 2.5 mg l –1 has been proposed.…”

Section: Introductionmentioning

confidence: 99%

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Pre‐dose plasma concentration monitoring of mycophenolate mofetil in patients with autoimmune diseases

Streicher

Djabarouti

Xuereb

et al. 2014

Brit J Clinical Pharma

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Aim To date, neither the benefit of mycophenolic acid (MPA) therapeutic drug monitoring (TDM), the prodrug of mycophenolate mofetil (MMF), nor the optimal monitoring technique have been established in autoimmune diseases. This study was undertaken to confirm, in a cohort of new patients, the plasma MPA thresholds previously published in patients with systemic lupus erythematosus (SLE) or vasculitis. Methods MPA areas under the concentration–time curves between 0 and 12 h, 12 h trough concentrations and pre‐dose concentrations (C0) were determined for 23 patients with SLE and 21 with systemic vasculitis. The relationship between patients' pharmacokinetic (PK) variables and their clinical outcomes during follow‐up were analyzed. Results In both autoimmune diseases, at PK assessment, median MPA C0 for patients with uncontrolled disease was significantly lower than that of patients with stable disease or in remission, 1.6 mg l–1 (IQR 0.9–2.1 mg l–1) vs. 2.95 mg l–1 (IQR 1.38–3.73 mg l–1) for SLE (P = 0.048) and 1.55 mg l–1 (IQR 0.98–2.18 mg l–1) vs. 3 mg l–1 (IQR 2.2–4.4 mg l–1) for vasculitis (P = 0.016). According to our receiver operating characteristics curve analysis, a C0 threshold of 2.5–3 mg l–1 was best able to discriminate a flare (SLE: 88% sensitivity, 80% specificity; vasculitis: 100% sensitivity, 90% specificity). Patients with C0 ≥ 2.5–3 mg l–1 at inclusion had better clinical outcomes during the 12 months following PK assessment. Conclusion Provided that the benefit of TDM in patients with autoimmune diseases could be confirmed by randomized, controlled trials, it might be based on the C0 measured approximately 12 h post‐dose.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 72%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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