Background

Mycophenolate mofetil (MMF) is theoretically a treatment of choice for mucous membrane pemphigoid (MMP), due to its good long-term tolerance and efficacy especially in elderly patients. However, no therapeutic monitoring is currently performed despite its large inter-individual variability.

Objectives

The aim of this study was to investigate the exposure/effect relationship based on the area under the curve (AUC) or trough level of mycophenolic acid in MMP patients.

Methods

Thirteen patients (n = 29 AUC measurements performed between February 2013 and November 2016) treated for MMP at Limoges University Hospital were evaluated using the Mucous Membrane Pemphigoid Disease Area Index score, and patients were classified as improvement (>50% decrease vs. baseline) vs. stabilisation (<50%) or non-response (no improvement). AUC was estimated using a population pharmacokinetic model and Bayesian estimation. The association between exposure parameters, demographic variables and response group was investigated using time-dependent Cox models, and an AUC threshold for ‘improvement’ was also investigated.

Results

An improvement was observed in approximately 70% of the patients. Only the MPA AUC0–24 h was retained in the multivariate analysis with a decreased risk of stabilisation/non-response per 10 mg*h/L increase, (HR = 0.64, 95% CI = [0.43–0.94], P = 0.0038). That led to an AUC0–24 h threshold of 89 mg*h/L associated with excellent performances (AUC ROC = 0.828, Sen = 75%, Spe = 100%, P = 0.0001).

Discussion/Conclusion

An association between MPA exposure and disease was observed. Therapeutic drug monitoring can be proposed with an AUC0–24 h threshold of 89 mg*h/L. It might improve the long-term response of patients to this drug with better tolerance than rituximab or cyclophosphamide.