Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.
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.
de Groot
Kirsten
K
Klinikum Offenbach, Offenbach, Germany.
Harper
Lorraine
L
Jayne
David R W
DR
Flores Suarez
Luis Felipe
LF
Gregorini
Gina
G
Gross
Wolfgang L
WL
Luqmani
Rashid
R
Pusey
Charles D
CD
Rasmussen
Niels
N
Sinico
Renato A
RA
Tesar
Vladimir
V
Vanhille
Philippe
P
Westman
Kerstin
K
Savage
Caroline O S
CO
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
D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D011239:Prednisolone