Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial

PLoS One. 2017 Oct 10;12(10):e0185880. doi: 10.1371/journal.pone.0185880. eCollection 2017.


Objectives: The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV.

Methods: In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity.

Results: Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed.

Conclusions: MTX may be effective and safe for remission-maintenance in AAV.

Trial registration: NCT00751517.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / complications
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / mortality
  • Antibodies, Antineutrophil Cytoplasmic / blood
  • Churg-Strauss Syndrome / complications
  • Churg-Strauss Syndrome / drug therapy*
  • Churg-Strauss Syndrome / immunology
  • Churg-Strauss Syndrome / mortality
  • Cyclophosphamide / therapeutic use*
  • Female
  • Granulomatosis with Polyangiitis / complications
  • Granulomatosis with Polyangiitis / drug therapy*
  • Granulomatosis with Polyangiitis / immunology
  • Granulomatosis with Polyangiitis / mortality
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Methotrexate / therapeutic use*
  • Microscopic Polyangiitis / complications
  • Microscopic Polyangiitis / drug therapy*
  • Microscopic Polyangiitis / immunology
  • Microscopic Polyangiitis / mortality
  • Middle Aged
  • Patient Safety
  • Patient Selection
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / immunology
  • Peripheral Nervous System Diseases / mortality
  • Proteinuria / complications
  • Proteinuria / drug therapy
  • Proteinuria / immunology
  • Proteinuria / mortality
  • Random Allocation
  • Recurrence
  • Remission Induction
  • Survival Analysis
  • Treatment Outcome


  • Antibodies, Antineutrophil Cytoplasmic
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Methotrexate

Associated data


Grant support

The author(s) received no specific funding for this work.