Effectiveness of Mycophenolate Mofetil Trough Level Monitoring in Children with Relapsing Nephrotic Syndrome

Key Points Therapeutic drug monitoring on the basis of mycophenolic acid (MPA) trough levels is associated with higher effectiveness of mycophenolate mofetil in maintaining remission in children with steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome. Dose adjustments on the basis of MPA trough levels personalize treatment, are associated with higher effectiveness, and help minimize potential toxicity. Maintaining MPA trough levels above 2.9 µ g/ml provides a relapse-free survival rate more than 85%, similar to that of more toxic drugs. Background The effectiveness of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) trough levels in children with steroid-dependent nephrotic syndrome (SDNS)/frequently relapsing nephrotic syndrome (FRNS) treated with mycophenolate mofetil (MMF) has not been adequately assessed. Methods We performed an international, retrospective study including children with SDNS/FRNS treated with MMF as the first-line steroid-sparing agent and a follow-up of more than 6 months. Patients were categorized into two groups: TDM, if MPA trough levels were monitored, and no-TDM, if not. In the TDM group, MMF doses were adjusted to maintain MPA trough levels of more than 3 µ g/ml, unless toxicity occurred. The primary outcome was relapse-free survival. Results A total of 167 patients were observed, 90 in the TDM group and 77 in the no-TDM group. Relapse-free survival over the total follow-up was significantly longer in the TDM group ( P = 0.001, log-rank test) with an estimated relapse-free survival at 6 months of 73% for the TDM group and 55% for the no-TDM group. After correcting for potential confounders, the association remained statistically significant ( P < 0.001). TDM patients also received lower doses of prednisone after MMF introduction. In the TDM group, children were more likely to modify their initial dose (90% versus 9%; P < 0.001). Although MMF dose was not associated with relapse (median 1186 versus 1298 mg/m 2 ; P = 0.14), MPA trough levels were significantly higher in children who did not relapse (4.0 versus 2.7 µ g/ml, P = 0.001). Among children maintaining mean MPA levels more than 2.9 µ g/ml, relapse-free survival at 6 months was 86%. Reported side effects were similar in both groups. Conclusions Monitoring MPA trough levels was associated with an approximately 20% higher MMF effectiveness in maintaining remission at 6 months in children with SDNS/FRNS. Personalized MMF dosing, adjusted to maintain MPA levels more than 2.9 µ g/ml, was both safe and effective. We recommend including MPA trough level monitoring in future studies comparing MMF with other steroid-sparing agents in children with SDNS/FRNS.