title: Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  42 centers in 12 European countries.
  
  
  METHODS
  149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease.
  
  
  METHODS
  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.
  
  
  METHODS
  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]).
  
  
  CONCLUSIONS
  The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  The European Union.
authors.affiliation: Klinikum Offenbach, Offenbach, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: de Groot
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
authors.forename: David R W
authors.initials: DR
authors.lastname: Jayne
authors.forename: Luis Felipe
authors.initials: LF
authors.lastname: Flores Suarez
authors.forename: Gina
authors.initials: G
authors.lastname: Gregorini
authors.forename: Wolfgang L
authors.initials: WL
authors.lastname: Gross
authors.forename: Rashid
authors.initials: R
authors.lastname: Luqmani
authors.forename: Charles D
authors.initials: CD
authors.lastname: Pusey
authors.forename: Niels
authors.initials: N
authors.lastname: Rasmussen
authors.forename: Renato A
authors.initials: RA
authors.lastname: Sinico
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tesar
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhille
authors.forename: Kerstin
authors.initials: K
authors.lastname: Westman
authors.forename: Caroline O S
authors.initials: CO
authors.lastname: Savage
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000150:complications / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D020551:Pulse Therapy, Drug; D012074:Remission Induction; D016896:Treatment Outcome; D014657:Vasculitis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011239:Prednisolone