Dr. de Groot has received speaking fees from Roche, Amgen, UCB, and Pfizer (less than $10,000 each).
Brief Report: Long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody–associated vasculitis
Article first published online: 27 SEP 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 10, pages 3472–3477, October 2012
How to Cite
Faurschou, M., Westman, K., Rasmussen, N., de Groot, K., Flossmann, O., Höglund, P., Jayne, D. R. W. and on behalf of the European Vasculitis Study Group (2012), Brief Report: Long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody–associated vasculitis. Arthritis & Rheumatism, 64: 3472–3477. doi: 10.1002/art.34547
- Issue published online: 27 SEP 2012
- Article first published online: 27 SEP 2012
- Accepted manuscript online: 21 MAY 2012 10:55AM EST
- Manuscript Accepted: 10 MAY 2012
- Manuscript Received: 11 OCT 2011
- European Community Systemic Vasculitis Trial project. Grant Numbers: BMH1-CT93-1078, CIPD-CT94-0307
- European Union (Associated Vasculitis European Randomized Trial project). Grant Numbers: BMH4-CT97-2328, IC20-CT97-0019
- Danish Arthritis Society
- Region Skane
- Cambridge Biomedical Research Centre
The NORAM (Nonrenal Wegener's Granulomatosis Treated Alternatively with Methotrexate [MTX]) trial demonstrated that MTX can replace cyclophosphamide (CYC) as remission-inducing treatment for patients with newly diagnosed early systemic antineutrophil cytoplasmic antibody–associated vasculitis. Duration of relapse-free survival was longer among CYC-treated patients than among MTX-treated patients during short-term followup. The aim of the present study was to describe the long-term outcome in patients enrolled in the randomized clinical trial.
Outcome questionnaires were sent to investigators who had recruited patients for the NORAM trial. Patients treated with MTX for induction of remission (n = 49) were compared to CYC-treated patients (n = 46) with respect to immunosuppressive therapy during followup, relapse-free survival, mortality, and occurrence of other clinical events.
The median duration of followup was 6 years (range 0.1–10.8 years). One patient developed end-stage renal disease, and 11 died. The number of patients affected by serious infection, malignancy, or severe organ failure did not differ between treatment groups, and no difference in survival rate was observed. The duration of corticosteroid therapy was longer in the MTX group during the 18 months of the trial (P = 0.005). During subsequent followup, patients who were in the MTX group in the NORAM trial received corticosteroids, CYC, and other immunosuppressive agents (azathioprine, MTX, and/or mycophenolate mofetil) for longer periods than those who were in the CYC group (P = 0.004, P = 0.037, and P = 0.031, respectively). The cumulative relapse-free survival tended to be lower in the MTX group (P = 0.056).
In the NORAM cohort, no difference in occurrence of major adverse events was observed between treatment groups during long-term followup. However, first-line treatment with MTX was associated with less effective disease control than CYC-based induction therapy.