Association between mycophenolic acid 12-h trough levels and clinical endpoints in patients with autoimmune disease on mycophenolate mofetil

Abstract

Background: Triggered by heightened interest in mycophenolate mofetil (MMF) for the treatment of autoimmune diseases (AID) and encouraged by the results from a previous study, we hypothesized that therapeutic drug monitoring of mycophenolic acid (MPA) based on troughs may be useful for effective MMF dosing in patients with AID.

Methods: A two-step approach was pursued. First, we confirmed in 38 AID patients (26 with antineutrophil cytoplasmic antibody-associated vasculitis; 12 with systemic lupus erythematosus) a significant correlation (r = 0.545, P < 0.001) between MPA C(12 h) and MPA exposure (AUC). Second, we performed an analysis of 294 MPA 12-h trough levels serially collected from 39 patients (same indications) receiving MMF for remission maintenance therapy to elucidate possible associations with disease activity and MMF toxicity.

Results: Higher MPA trough levels were associated with better protection from recurrence of active disease. While at levels <3 mg/L 29% of collected samples (43/147) were from patients with active disease, this was only the case in 2% of samples (3/147) with an MPA concentration of >or=3 mg/L. Remission persisted in all patients with MPA troughs >or=3.5 mg/L. Upon combined analysis of efficacy and safety data, most favourable results were obtained with MPA troughs between 3.5 and 4.5 mg/L. There was no discernable relationship between MMF dose and clinical endpoints.

Conclusion: The target range proposed by this explorative study may serve as an initial guidance for MPA monitoring in the context of further prospective controlled trials in patients with AID.