The role of mycophenolate in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis

Abstract

Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.

Keywords: Mycophenolic acid; Mycophenolate mofetil; Mycophenolate sodium; Antineutrophil cytoplasmic antibody-associated vasculitis; Microscopic polyangiitis; Granulomatosis with polyangiitis; Induction; Remission; Relapse

Core tip: Antineutrophil cytoplasmic antibody-associated vasculitis is characterized by a remitting - relapsing course of disease that requires long term immunosuppression. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antibody-associated vasculitis as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate has been proven a potent immunosuppressive agent and non-inferior to other available drugs with comparable side effect profile, but several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects. In this review, the role of mycophenolate in treatment of antibody-associated vasculitis is further discussed.