Background:
Cyclophosphamide induction regimens for antineutrophil cytoplasmic antibody (anca)-associated vasculitis are effective in 70 to 90% of patients, but they are associated with high rates of death and adverse events. treatment with rituximab has led to remission rates of 80 to 90% among patients with refractory anca-associated vasculitis and may be safer than cyclophosphamide regimens.
Methods:
We compared rituximab with cyclophosphamide as induction therapy in anca-associated vasculitis. we randomly assigned, in a 3:1 ratio, 44 patients with newly diagnosed anca-associated vasculitis and renal involvement to a standard glucocorticoid regimen plus either rituximab at a dose of 375 mg per square meter of body-surface area per week for 4 weeks, with two intravenous cyclophosphamide pulses (33 patients, the rituximab group), or intravenous cyclophosphamide for 3 to 6 months followed by azathioprine (11 patients, the control group). primary end points were sustained remission rates at 12 months and severe adverse events.
Results:
The median age was 68 years, and the glomerular filtration rate (gfr) was 18 ml per minute per 1.73 m(2) of body-surface area. a total of 25 patients in the rituximab group (76%) and 9 patients in the control group (82%) had a sustained remission (p=0.68). severe adverse events occurred in 14 patients in the rituximab group (42%) and 4 patients in the control group (36%) (p=0.77). six of the 33 patients in the rituximab group (18%) and 2 of the 11 patients in the control group (18%) died (p=1.00). the median increase in the gfr between 0 and 12 months was 19 ml per minute in the rituximab group and 15 ml per minute in the control group (p=0.14).
Conclusions:
A rituximab-based regimen was not superior to standard intravenous cyclophosphamide for severe anca-associated vasculitis. sustained-remission rates were high in both groups, and the rituximab-based regimen was not associated with reductions in early severe adverse events. (funded by cambridge university hospitals national health service foundation trust and f. hoffmann-la roche; current controlled trials number, isrctn28528813.)