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A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies

Jayne, David; Rasmussen, Niels; Andrassy, Konrad; Bacon, Paul; Tervaert, Jan Willem Cohen; Dadoniene, Jolanta; Ekstrand, Agneta; Gaskin, Gill; Gregorini, Gina and de Groot, Kirsten, et al. (2003) In New England Journal of Medicine 349(1). p.36-44
Abstract
BACKGROUND: The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission. METHODS: We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a... (More)
BACKGROUND: The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission. METHODS: We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point. RESULTS: Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03). CONCLUSIONS: In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced. (Less)
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New England Journal of Medicine
volume
349
issue
1
pages
36 - 44
publisher
Massachusetts Medical Society
external identifiers
  • wos:000183896100006
  • pmid:12840090
  • scopus:0038122889
ISSN
0028-4793
language
English
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yes
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eebda989-72d8-4cc4-b108-386f5695043e (old id 308393)
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2007-08-03 11:10:23
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2018-05-29 11:41:59
@article{eebda989-72d8-4cc4-b108-386f5695043e,
  abstract     = {BACKGROUND: The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission. METHODS: We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point. RESULTS: Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03). CONCLUSIONS: In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.},
  author       = {Jayne, David and Rasmussen, Niels and Andrassy, Konrad and Bacon, Paul and Tervaert, Jan Willem Cohen and Dadoniene, Jolanta and Ekstrand, Agneta and Gaskin, Gill and Gregorini, Gina and de Groot, Kirsten and Gross, Wolfgang and Hagen, E Christiaan and Mirapeix, Eduardo and Pettersson, Erna and Siegert, Carl and Sinico, Alberto and Tesar, Vladimir and Westman, Kerstin and Pusey, Charles},
  issn         = {0028-4793},
  language     = {eng},
  number       = {1},
  pages        = {36--44},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies},
  volume       = {349},
  year         = {2003},
}