Mycophenolic acid area under the curve is associated with therapeutic response in pediatric lupus nephritis
Introduction Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is an effective treatment in lupus nephritis. Therapeutic drug monitoring studies of MMF suggest that area under the concentration-time curve (AUC) values of MPA of 30–45mg.h/L may be associated with better outcome in adults with lupus but data in children is scarce. Methods In this retrospective study, 27 children were treated with MMF for biopsy proven class III–IV–V lupus nephritis between 2009 and 2016. AUC of MPA was determined on the basis of sampling times at 20, 60, and 180minutes post-dose using a Bayesian estimator. In 25 children, AUC was performed within 6 months after kidney biopsy and MMF initiation. Treatment response at 6 months of MMF treatment was defined as follows: normal or improved GFR by 25% compared to baseline, 50% reduction of proteinuria resulting in a level Results In total, 62 AUC of MPA were analyzed [median 44mg.h/L (IQR 33–54)] in 27 patients. The findings indicate individual dose adaptation in 32 cases (52%) to achieve an AUC target of 30–60mg.h/L. At 6 months, 14/25 patients were defined as responders (56%) with a median AUC value of 49 [40–59] and 11/25 as non-responders (44%) with a median AUC value of 29 [24–38]. Patients with MPA AUC levels of >45, 30–45, and 45 was significantly associated with therapeutic response (OR 3.9, 95% CI 2.4–10.5, P Conclusion Therapeutic drug monitoring leading to individualize dosing may improve the efficacy of MMF. An AUC of MPA >45mg.h/L is associated with a better response rate and may be considered as a target value in paediatric lupus nephritis.
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