Published in:
01-02-2021 | Systemic Lupus Erythematosus | Original Article
Mycophenolic acid area under the concentration-time curve is associated with therapeutic response in childhood-onset lupus nephritis
Published in: Pediatric Nephrology | Issue 2/2021
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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.