Exposure-response relationship of mycophenolic acid in pediatric lupus nephritis patients receiving multi-target therapy: An observational cohort study

Abstract

Objective

To establish the effectiveness threshold of mycophenolic acid-area under the concentration-time curve between 0 h and 12 h (MPA-AUC_{0–12 h}) in pediatric lupus nephritis (LN) patients receiving multi-target therapy.

Methods

This observational cohort study enrolled 48 pediatric LN patients treated with mycophenolate mofetil (MMF), tacrolimus, and prednisone. MPA-AUC_{0–12 h} was calculated using concentrations based on a limited sampling strategy. Binary logistic regression analysis was employed to investigate factors influencing efficacy. Receiver operating characteristic analysis was conducted to assess MPA-AUC_{0–12 h} threshold values. The cumulative incidence of renal remission and inactive systemic lupus erythematosus (SLE) over time was evaluated using Kaplan-Meier analysis. The t-test or Mann-Whitney test was utilized for comparisons between two groups of continuous variables.

Results

To achieve renal remission, the MPA-AUC_{0–12 h} threshold at 6 months was determined to be 25.24 μg·h·mL⁻¹, with an area under the ROC curve (AUC) of 0.83 (P = 0.0002). At 12 months, the MPA-AUC threshold decreased to 23.52 μg·h·mL⁻¹, yielding an AUC of 0.89 (P < 0.0001). For inactive SLE, the MPA-AUC_{0–12 h} threshold at 6 months was found to be 31.16 μg·h·mL⁻¹, with an AUC of 0.80 (P = 0.0004), while at 12 months it decreased slightly to 28.87 μg·h·mL⁻¹, resulting in an AUC of 0.82 (P = 0.0012). Patients who reached target thresholds for MPA-AUC_{0–12 h} achieved renal response or inactive SLE more rapidly.

Conclusion

There is a significant correlation between MPA-AUC_{0–12 h} and treatment response in pediatric LN patients receiving multi-target therapy; therefore, it is recommended that MMF dosing be adjusted according to individual MPA-AUC_{0–12 h} levels.