Gliptin-induced bullous pemphigoid: withdrawal of gliptin allows for faster control of the disease

Background: Gliptins, also called dipeptidyl peptidase-4 inhibitors, have been incriminated in the development of bullous pemphigoid (BP). To date, there are no recommendations regarding the therapeutic approach for BP during gliptin intake. Objectives: The aim of this retrospective study was to evaluate the evolution of BP after three months relative to continuation or discontinuation of gliptin. Materials & Methods: From a series of 372 patients with BP, 40 taking gliptin were included (January 2009 to December 2019). The primary endpoint was complete response, three months after BP diagnosis based on gliptin continuation or discontinuation. The secondary endpoints were complete response after one month and six months. Results: Of BP patients, 67.5% were taking vildagliptin. BP was diagnosed at a mean period of 28.8 months after gliptin initiation. Gliptin was continued and discontinued each in 20 patients. Three months after diagnosis, patients who stopped gliptin had a significatively better clinical status (p = 0.0006). Thirteen patients had complete response when gliptin was stopped, compared to one patient when gliptin was continued. This difference was maintained after six months (p = 0.0031). There was no difference between the treatments received by patients who stopped gliptin and those who continued treatment (p = 0.7515). Conclusion: In this retrospective study, two groups were compared; one that continued gliptin and the other that stopped the drug. The results obtained suggest that stopping gliptin allows for a complete response rate at three months and six months, whereas gliptin maintenance did not allow for complete response.

Towards therapeutic drug monitoring of mycophenolic acid in mucous membrane pemphigoid: A retrospective single-centre study.

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.