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Pulse Versus Daily Oral Cyclophosphamide for Induction of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis A Randomized Trial

de Groot, Kirsten; Harper, Lorraine; Jayne, David R. W.; Suarez, Luis Felipe Flores; Gregorini, Gina; Gross, Wolfgang L.; Luqmani, Rashid; Pusey, Charles D.; Rasmussen, Niels and Sinico, Renato A., et al. (2009) In Annals of Internal Medicine 150(10). p.3-670
Abstract
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... (More)
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. (Less)
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Annals of Internal Medicine
volume
150
issue
10
pages
3 - 670
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American College of Physicians
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  • wos:000266285300002
  • scopus:66149168812
ISSN
0003-4819
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English
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5726a920-31ef-404a-b2a3-3a6e4ecca81b (old id 1425434)
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http://www.annals.org/content/150/10/670
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2009-07-02 10:32:07
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@article{5726a920-31ef-404a-b2a3-3a6e4ecca81b,
  abstract     = {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 &lt; 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.},
  author       = {de Groot, Kirsten and Harper, Lorraine and Jayne, David R. W. and Suarez, Luis Felipe Flores and Gregorini, Gina and Gross, Wolfgang L. and Luqmani, Rashid and Pusey, Charles D. and Rasmussen, Niels and Sinico, Renato A. and Tesar, Vladimir and Vanhille, Philippe and Westman, Kerstin and Savage, Caroline O. S.},
  issn         = {0003-4819},
  language     = {eng},
  number       = {10},
  pages        = {3--670},
  publisher    = {American College of Physicians},
  series       = {Annals of Internal Medicine},
  title        = {Pulse Versus Daily Oral Cyclophosphamide for Induction of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis A Randomized Trial},
  volume       = {150},
  year         = {2009},
}