ESPN 50th Annual Meeting

ESPN 2017


 
Mycophenolic acid area under the curve is associated with therapeutic response in pediatric lupus nephritis
ASTRID DUBRASQUET 1 STéPHANE DECRAMER 2 MARC FILA 3 VINCENT GUIGONIS 4 STEPHANIE TELLIER 2 DENIS MORIN 3 FRANCK SAINT-MARCOUX 4 JEROME HARAMBAT 1

1- BORDEAUX UNIVERSITY HOSPITAL
2- TOULOUSE UNIVERSITY HOSPITAL
3- MONTPELLIER UNIVERSITY HOSPITAL
4- LIMOGES UNIVERSITY HOSPITAL
 
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 may be associated with clinical outcome in adults with lupus but data in children is scarce.

Material and methods:

In this retrospective study, 27 children with biopsy proven class III-IV-V lupus nephritis were treated with MMF in 2009-2016. AUC of MPA was determined on the basis of sampling times at 20, 60, and 180 minutes postdose 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 <0.5 g/day or 50 mg/mmol, no hematuria (red blood cells <10000/ml or ≤1+ by dipstick).

Results:

A total of 62 MPA-AUC were analyzed (median 44 mg.h/L [IQR 33-54]) in 27 patients. Individual dose adaptation was required in 32 cases (52%) to achieve a target AUC of 30-60 mg.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 <30 had response rates of 89% (8/9), 60% (6/10) and 0% (0/6) at 6 months. In a logistic regression model adjusted for age, sex, disease classification and time since MMF, an AUC >45 was significantly associated with therapeutic response (OR 3.9, CI95% 2.4-10.5, p<0.03).

Conclusions:

Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of MMF. An AUC of MPA >45 mg.h/L is associated with a better response rate and migt be considered as a target value in pediatric lupus nephritis.