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.
RCT Entities:
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.
Authors: Megan E B Clowse; Susannah C Copland; Tsung-Cheng Hsieh; Shein-Chung Chow; Gary S Hoffman; Peter A Merkel; Robert F Spiera; John C Davis; W Joseph McCune; Steven R Ytterberg; E William St Clair; Nancy B Allen; Ulrich Specks; John H Stone Journal: Arthritis Care Res (Hoboken) Date: 2011-12 Impact factor: 4.794
Authors: Ravi Suppiah; Oliver Flossman; Chetan Mukhtyar; Federico Alberici; Bo Baslund; Denise Brown; Nadeem Hasan; Julia Holle; Zdenka Hruskova; David Jayne; Andrew Judge; Mark A Little; Peter A Merkel; Alessandra Palmisano; Philip Seo; Coen Stegeman; Vladimir Tesar; Augusto Vaglio; Kerstin Westman; Raashid Luqmani Journal: Ann Rheum Dis Date: 2010-08-24 Impact factor: 19.103
Authors: Michael Walsh; Fausta Catapano; Wladimir Szpirt; Kristian Thorlund; Annette Bruchfeld; Loic Guillevin; Marion Haubitz; Peter A Merkel; Chen Au Peh; Charles Pusey; David Jayne Journal: Am J Kidney Dis Date: 2010-12-30 Impact factor: 8.860