Mycophenolic acid area under the concentration-time curve is associated with therapeutic response in childhood-onset lupus nephritis - Individual Prediction and Prevention of Risks of Immunosuppressive Therapies in Transplantation Access content directly
Journal Articles Pediatric Nephrology Year : 2021

Mycophenolic acid area under the concentration-time curve is associated with therapeutic response in childhood-onset lupus nephritis

Abstract

Background: Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is widely used in lupus nephritis treatment. Therapeutic drug monitoring of adults suggests that area under the concentration-time curve (AUC) of MPA (MPA-AUC) is associated with clinical outcomes, but childhood data are scarce. Methods: Retrospective study of 27 children with biopsy-proven lupus nephritis treated with MMF between 2008 and 2016. In 25 children, MPA-AUC was performed within 6 months after kidney biopsy and MMF initiation. Treatment response at 6 months was defined as normal or improved GFR by 25% compared with baseline, 50% reduction of proteinuria to < 0.5 g/day or 50 mg/mmol, and no hematuria. Results: A total of 62 MPA-AUC were analyzed in 27 patients. Overall median was 44 mg h/L (interquartile range [IQR] 33-54). Individual dose adaptation was required in 32 cases (52%) to achieve target AUC of 30-60 mg h/L. At 6 months, 14/25 patients were defined as responders (56%, median MPA-AUC 49 mg h/L (40-59)) and 11/25 as non-responders (44%, 29 mg h/L (24-38)). Patients with MPA-AUC levels > 45, 30-45, and < 30 mg h/L had 6-month response rates of 89% (8/9), 60% (6/10), and 0% (0/6), respectively. In a logistic regression model adjusted for age, sex, lupus nephritis classification, and time since MMF initiation, an MPA-AUC > 45 mg h/L was significantly associated with therapeutic response (OR 3.6, 95% CI 2.4-9.5, p = 0.03). Conclusions: Therapeutic drug monitoring leading to individualized dosing may improve efficacy of MMF. MPA-AUC > 45 mg h/L is associated with better response rate and may be considered as a target value in pediatric lupus nephritis.
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Dates and versions

hal-03652633 , version 1 (26-04-2022)

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Astrid Godron-Dubrasquet, Jean-Baptiste Woillard, Stéphane Decramer, Marc Fila, Vincent Guigonis, et al.. Mycophenolic acid area under the concentration-time curve is associated with therapeutic response in childhood-onset lupus nephritis. Pediatric Nephrology, 2021, 36 (2), pp.341-347. ⟨10.1007/s00467-020-04733-x⟩. ⟨hal-03652633⟩
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