Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
BACKGROUND
Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen.


METHODS
We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months.


RESULTS
Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events.


CONCLUSIONS
Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)
Stone
John H
JH
Massachusetts General Hospital, Boston, USA.
Merkel
Peter A
PA
Spiera
Robert
R
Seo
Philip
P
Langford
Carol A
CA
Hoffman
Gary S
GS
Kallenberg
Cees G M
CG
St Clair
E William
EW
Turkiewicz
Anthony
A
Tchao
Nadia K
NK
Webber
Lisa
L
Ding
Linna
L
Sejismundo
Lourdes P
LP
Mieras
Kathleen
K
Weitzenkamp
David
D
Ikle
David
D
Seyfert-Margolis
Vicki
V
Mueller
Mark
M
Brunetta
Paul
P
Allen
Nancy B
NB
Fervenza
Fernando C
FC
Geetha
Duvuru
D
Keogh
Karina A
KA
Kissin
Eugene Y
EY
Monach
Paul A
PA
Peikert
Tobias
T
Stegeman
Coen
C
Ytterberg
Steven R
SR
Specks
Ulrich
U
D000284:Administration, Oral; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000187:drug effects; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D055953:Microscopic Polyangiitis / Q000188:drug therapy*; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology; D011241:Prednisone / Q000627:therapeutic use; D011788:Quality of Life; D012074:Remission Induction; D000069283:Rituximab
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D011241:Prednisone; D008775:Methylprednisolone