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Previous Volume 359:2790-2803 December 25, 2008 Number 26 Next

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ABSTRACT

Background Current standard therapy for Wegener's granulomatosis and microscopic polyangiitis combines corticosteroids and cyclophosphamide to induce remission, followed by a less toxic immunosuppressant such as azathioprine or methotrexate for maintenance therapy. However, azathioprine and methotrexate have not been compared with regard to safety and efficacy.

Methods In this prospective, open-label, multicenter trial, we randomly assigned patients with Wegener's granulomatosis or microscopic polyangiitis who entered remission with intravenous cyclophosphamide and corticosteroids to receive oral azathioprine (at a dose of 2.0 mg per kilogram of body weight per day) or methotrexate (at a dose of 0.3 mg per kilogram per week, progressively increased to 25 mg per week) for 12 months. The primary end point was an adverse event requiring discontinuation of the study drug or causing death; the sample size was calculated on the basis of the primary hypothesis that methotrexate would be less toxic than azathioprine. The secondary end points were severe adverse events and relapse.

Results Among 159 eligible patients, 126 (79%) had a remission, were randomly assigned to receive a study drug in two groups of 63 patients each, and were followed for a mean (±SD) period of 29±13 months. Adverse events occurred in 29 azathioprine recipients and 35 methotrexate recipients (P=0.29); grade 3 or 4 events occurred in 5 patients in the azathioprine group and 11 patients in the methotrexate group (P=0.11). The primary end point was reached in 7 patients who received azathioprine as compared with 12 patients who received methotrexate (P=0.21), with a corresponding hazard ratio for methotrexate of 1.65 (95% confidence interval, 0.65 to 4.18; P=0.29). There was one death in the methotrexate group. Twenty-three patients who received azathioprine and 21 patients who received methotrexate had a relapse (P=0.71); 73% of these patients had a relapse after discontinuation of the study drug.

Conclusions These results do not support the primary hypothesis that methotrexate is safer than azathioprine. The two agents appear to be similar alternatives for maintenance therapy in patients with Wegener's granulomatosis and microscopic polyangiitis after initial remission. (ClinicalTrials.gov number, NCT00349674 [ClinicalTrials.gov] .)

Source Information

From Université Paris Descartes, Hôpital Cochin, Assistance Publique–Hôpitaux de Paris (C.P., A.M., P.C., L.M., L.G.), Hôpital Tenon (J.-J.B.), and Hôpital Bichat–Claude-Bernard (T.P.) — all in Paris; Centre Hospitalier Universitaire Hôtel-Dieu, Nantes (M.A.H.); Centre Hospitalier Universitaire Hôtel-Dieu, Clermont-Ferrand (M.R.); Hôpital Nord, Amiens (J.-P.D.); Centre Hospitalier de Valenciennes, Valenciennes (X.K.); Centre Hospitalier de Dax, Dax (F.L.); Centre Hospitalier Régional Universitaire de Lille, Lille (M.L.); Centre Hospitalier de Cholet, Cholet (J.L.N.); Hôpital Henri-Mondor, Créteil (M.K.); Centre Hospitalier de Compiègne, Compiègne (D.M.); Centre Hospitalier du Mans, Le Mans (X.P.); Hôpital Hautepierre, Strasbourg (S.V.); and Hôpital Louis-Pradel, Université Lyon I, Lyon (J.-F.C.) — all in France.

Address reprint requests to Dr. Pagnoux at the National Referral Center for Rare Systemic and Autoimmune Diseases, Necrotizing Vasculitides, and Systemic Sclerosis, Department of Internal Medicine, Hôpital Cochin, 27, Rue du Faubourg Saint-Jacques, 75679 Paris CEDEX 14, France, or at christian.pagnoux{at}cch.aphp.fr.

Full Text of this Article

Related Letters:

Azathioprine or Methotrexate Maintenance for ANCA-Associated Vasculitis
Jourde N., Mancini J., Chiche L., Gelber A. C., Pagnoux C., Guillevin L., the French Vasculitis Study Group and the Wegener's Granulomatosis–Entretien (WEGENT) Investigators
Extract | Full Text | PDF  
N Engl J Med 2009; 360:1358-1359, Mar 26, 2009. Correspondence

This article has been cited by other articles:

• Jourde, N., Mancini, J., Chiche, L., Gelber, A. C., Pagnoux, C., Guillevin, L., the French Vasculitis Study Group and the Wegener', (2009). Azathioprine or methotrexate maintenance for ANCA-associated vasculitis.. NEJM 360: 1358-1359 [Full Text]  
• Specks, U. (2009). Pulmonary Vasculitis and Alveolar Hemorrhage Syndromes. ACCP Pulmonary Med Brd Rev 25: 687-704 [Full Text]  
• (2008). Maintenance Therapy for ANCA-Associated Vasculitis -- Azathioprine or Methotrexate?. Journal Watch Dermatology 2008: 1-1 [Full Text]