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Jayne and associates studied whether it was possible to substitute a regimen of azathioprine at 2 mg/kg per day for maintenance therapy in patients with generalized vasculitis.
Maintenance Therapy for Vasculitis Associated with Antineutrophil Cytoplasmic Autoantibodies
August 1, 2003 2 minutes read
Abstract & Commentary
Source: Jayne D, et al. A randomized trial of maintenance therapy for vasculitis associated with antineurotrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36-44.
The treatment of a variety of forms of CNS vasculitis is difficult. Two types can characterized by positivity to antineutrophil cytoplasmic antibodies. These are Wegener’s granulomatosis and microscopic polyangiitis. These illnesses share several common features including pulmonary capillaritis, glomerulonephritis, and the circulating antineutrophil cytoplasmic antibodies that are positive for either proteinase-3 or myeloperoxidase. Modern treatment for these illnesses was established in the early 1970s when Fauci and associates introduced a regimen combining daily cyclophosphamide therapy given for 1 year after remission was achieved with prednisone therapy initiated at a dose of 1 mg/kg of body weight per day and then tapered to an alternate day schedule.1-2 This treatment has produced remission in 80-100% of patients and can result in long-term survival. One difficulty, however, is that many patients relapsed when they were discontinued from therapy. Relapse occurred in almost 50% of patients by 8 years. In the present report, Jayne and associates studied whether it was possible to substitute a regimen of azathioprine at 2 mg/kg per day for maintenance therapy in patients with generalized vasculitis. Both groups continued to receive prednisolone. In this study, the patients all received initially 3 months of oral cyclophosphamide and prednisolone and then were randomized to either 1.5 mg/kg per day of cyclophosphamide or 2 mg/kg per day of the azathioprine, which was then continued up to 18 months from study entry. Relapse was the primary end point. The number of serious adverse side effects was similar in the 2 groups. The relapse rate was lower among patients with microscopic polyangiitis than among those with Wegener’s granulomatosis. The substitution of azathioprine after remission did not, however, increase the rate of relapse.
Commentary
This appears to be a new and reasonable approach to more chronic treatment of patients with vasculitis. Exactly how long azathioprine therapy should then be maintained remains to be determined. Nevertheless, the lower toxicity of azathioprine as compared to cyclophosphamide makes it a reasonable alternative treatment once remission has been induced with cyclophosphamide. — M. Flint Beal, MD. Dr. Beal, Department of Neurology; Cornell University Medical College, is Editor of Neurology Alert.
References
1. Fauci AS, et al. N Engl J Med. 1971;285:1493-1496.
2. Fauci AS, et al. Am J Med. 1978;64:890-894.
Jayne and associates studied whether it was possible to substitute a regimen of azathioprine at 2 mg/kg per day for maintenance therapy in patients with generalized vasculitis.
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