The clinical benefit of Therapeutic Drug Monitoring (TDM) of mycophenolate mofetil (MMF) when used in children with lupus (SLE) has been scarcely studied.

(i) To model mycophenolic acid (MPA; the active moiety of MMF) pharmacokinetic profiles (PK); (ii) to explore the relationships between exposure indices to MPA and the clinical status.in paediatric inpatients with SLE receiving a maintenance immunosuppressive therapy including MMF.

We launched a non-interventional study with analysis of clinical, biological and pharmacokinetic information. Full-PK profiles of MPA were modelled using an iterative two-stage approach (1). The clinical status was defined by the SLEDAI, the SLE being considered active for a score ≥6. Relationships between MPA through concentrations (C₀), AUC (Area Under Curve) or AUC/dose values, and the disease’s activity were studied using logistic regression analysis.

Twenty six children (aged 10 to 17) with SLEDAI score from 0 to 20 (median: 4) followed-up in 5 French centres were included. High PK interpatient variability was observed: AUC_0-12h=40.51±20.49 mg.h/L. Trough concentrations (C₀) were poorly correlated to the global exposure to MPA (AUC). Multivariate analysis reported: (i) no relationship between C₀ and SLEDAI; (ii) patients with an AUC_0-12h/dose <0.058 h/L were more likely to have an active disease (OR=4.8; 95CI: 0.9-25.0; p=0.067).

A tendency to a relationship between the lupus activity and the global MPA exposure was observed. Further data are needed to develop PK tools that could estimate the AUC using a limited sampling strategy and to lead prospective trials testing the clinical impact of a MMF TDM based on the AUC.