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

backgroundMycophenolic 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.

methodsRetrospective 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.

resultsA 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).

conclusionsTherapeutic 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.