Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial

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  • European Vasculitis Study Group (EUVAS)
  • Rachel B. Jones
  • Thomas F Hiemstra
  • Jose Ballarin
  • Daniel Engelbert Blockmans
  • Paul Brogan
  • Annette Bruchfeld
  • Maria C. Cid
  • Karen Dahlsveen
  • Janak de Zoysa
  • Georgína Espigol-Frigolé
  • Peter Lanyon
  • Chen Au Peh
  • Vladimir Tesar
  • Augusto Vaglio
  • Michael Walsh
  • Dorothy Walsh
  • Giles Walters
  • Lorraine Harper
  • David Jayne

Colleges, School and Institutes



Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV.



We conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR <15 mL/min were excluded from the study.



At baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90%CI −7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95%CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3).



MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate.


Trial registration number 



Original languageEnglish
Pages (from-to)399-405
JournalAnnals of the Rheumatic Diseases
Issue number3
Early online date5 Jan 2019
Publication statusPublished - Mar 2019


  • ANCA-associated vasculitis, cyclophosphamide, induction therapy, mycophenolate, randomised trial