Pharmacokinetic evaluation of mycophenolate mofetil for pemphigus

Abstract

Introduction: Pemphigus is an autoimmune blistering disease of the skin and mucous membranes characterized by the development of autoantibodies against the desmosomal proteins, desmoglein-1 and -3. Before the advent of corticosteroids, therapy was almost fatal. The introduction of high-dose corticosteroid therapy has reduced mortality rates to ∼ 10%, but long-term use of steroids can lead to side effects, many of which are severe and associated with significant morbidity. Thus, the major goal of pemphigus therapy has been to reduce the patient's cumulative exposure to systemic corticosteroids. Over the last 2 decades, a range of corticosteroid-sparing immunosuppressive agents have been described, but these therapies are not without potentially serious complications. Despite the range of treatment options, a proportion of patients do not achieve remission, while others show an initial treatment response but remain poorly controlled. The recent availability of mycophenolate mofetil (MMF), originally developed for preventing allograft rejection, appears to be effective in autoimmune blistering diseases in combination with systemic corticosteroid or as a monotherapy.

Areas covered: This review aims to provide an extensive overview of the literature on the clinical pharmacokinetics of MMF in pemphigus treatment and a brief summary of current pharmacodynamic information. After completing this learning activity, readers should be able to summarize the pharmacology of MMF as an immunosuppressant; recognize its potential role in the treatment of pemphigus, including general dosing guidelines and laboratory monitoring schedules, use in patient populations and potential adverse effects; and identify future considerations and developing areas of research regarding the use of mycophenolic acid in the treatment of autoimmune blistering diseases.

Expert opinion: Current morbidity of pemphigus is largely iatrogenic, caused by side effects of the long-term, high-dose corticosteroid therapy that is necessary to sustain disease control. MMF demonstrates complex pharmacokinetics and displays large between-subject pharmacokinetic variability. Experience with MMF has demonstrated long-term safety and tolerability in the treatment of pemphigus.

Keywords::

• immunosuppressant
• inosine monophosphate dehydrogenase
• mycophenolate mofetil
• mycophenolic acid
• pemphigus pharmacokinetic
• treatment