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

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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. 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 6months after kidney biopsy and MMF initiation. Treatment response at 6months was defined as normal or improved GFR by 25% compared with baseline, 50% reduction of proteinuria to < 0.5g/day or 50mg/mmol, and no hematuria. A total of 62 MPA-AUC were analyzed in 27 patients. Overall median was 44mgh/L (interquartile range [IQR] 33-54). Individual dose adaptation was required in 32 cases (52%) to achieve target AUC of 30-60mgh/L. At 6months, 14/25 patients were defined as responders (56%, median MPA-AUC 49mgh/L (40-59)) and 11/25 as non-responders (44%, 29mgh/L (24-38)). Patients with MPA-AUC levels > 45, 30-45, and < 30mgh/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 > 45mgh/L was significantly associated with therapeutic response (OR 3.6, 95% CI 2.4-9.5, p= 0.03). Therapeutic drug monitoring leading to individualized dosing may improve efficacy of MMF. MPA-AUC > 45mgh/L is associated with better response rate and may be considered as a target value in pediatric lupus nephritis.