Mycophenolate Mofetil vs Azathioprine for Remission Maintenance in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Abstract

NTINEUTROPHIL CYTOPLASmic antibodies (ANCAs) are frequently found in patients with Wegener granulomatosis and microscopic polyangiitis. Together, Wegener granulomatosis and microscopic polyangiitis are considered ANCA-associated vasculitis (AAV) due to their similarity in clinical and histological features, prognosis, and treatment. Standard therapy for patients with AAV consists of induction of remission with cyclophosphamide and glucocorticoids, followed by remission maintenance with azathioprine or methotrexate and a tapering course of glucocorticoids. 1,2 Relapses of AAV occur in 50% of patients within 5 years of diagnosis, and treatment toxicity is common. 3,4 Safe and effective therapies to maintain remission of AAV are a priority. For editorial comment see p 2413.

Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study

“…Oral cyclophosphamide or azathioprine was indicated as an immunosuppressive agent during remission maintenance in the JMAAV protocol, but the agents were employed at the discretion of the attending physician. As the CYCAZAREM, WEGENT (Wegener’s granulomatosis-entretien trial) [19], and IMPROVE (international mycophenolate protocol to reduce outbreaks of vasculitides randomized trial) trials [20] have indicated that azathioprine is the best adjunctive immunosuppressant during maintenance treatment, the use of this agent for MPA patients should be analyzed in future trials. In addition, a tapering protocol was not determined in the JMAAV trial, and therefore the total amounts of glucocorticoid administered were greater than those outlined in the European recommendations (data not shown).…”

Lower 12-hour Trough Concentrations of Mycophenolic Acid in Patients with Active Systemic Vasculitides Taking Mycophenolate Mofetil

“…Hiemstra, et al conducted the first randomized controlled study of MMF therapy for AAV with longterm followup: contrary to what was initially thought, MMF at a starting fixed dose of 2 g/day, reduced to 1 g/day and withdrawn after 42 months, was less effective than azathioprine for maintaining remission 3 . That observation compromises its use as first-line maintenance therapy.…”

“…However, no recommendations concerning optimal dose of MMF for AAV are available, and a high relapse rate might compromise its use as a first-line remission-maintenance therapy 3 . An association between SLE activity and the pharmacokinetics of MPA has been described 4,5,6 .…”

“…Efficacy was assessed after at least 6 months of MMF use. At inclusion, remission was defined as Birmingham Vasculitis Activity Score 8 (BVAS) = 0, indicating no persistently active disease manifestations since the previous examination 1 month earlier 3 , and classifying patients as therapeutic successes. Patients whose disease was not controlled (BVAS ≥ 1) were considered failures.…”

Glomerulonephritis, Pathogenetic Mechanisms and Therapeutic Options: An Overview

“…Its use is still burdened with significant toxicity, so that, in recent years, its use was reduced. The comparison studies, performed both in ANCA associated vasculitis that in lupus glomerulonephritis, including AZA and mycophenolate mofetil (MMF) have reported equivalent results in terms of effectiveness, but most of the toxicity of AZA compared with MMF [1,[32][33][34][35][36].…”