Background:
Current therapies for antineutrophil cytoplasmic antibody (anca)-associated vasculitis are limited by toxicity.
Objective:
To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission.
Design:
Randomized, controlled trial. random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. patients, investigators, and assessors of outcomes were not blinded to assignment.
Setting:
42 centers in 12 european countries.
Patients:
149 patients who had newly diagnosed generalized anca-associated vasculitis with renal involvement but not immediately life-threatening disease.
Intervention:
Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone.
Measurement:
Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes).
Results:
Groups did not differ in time to remission (hazard ratio, 1.098 [95% ci, 0.78 to 1.55]; p = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; p < 0.001). the pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [ci, 0.23 to 0.71]).
Limitations:
The study was not powered to detect a difference in relapse rates between the 2 groups. duration of follow-up was limited.
Conclusion:
The pulse cyclophosphamide regimen induced remission of anca-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia.
Primary funding source:
The european union.