title: Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
abstract: 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.)
authors.affiliation: Massachusetts General Hospital, Boston, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.forename: Carol A
authors.initials: CA
authors.lastname: Langford
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: Anthony
authors.initials: A
authors.lastname: Turkiewicz
authors.forename: Nadia K
authors.initials: NK
authors.lastname: Tchao
authors.forename: Lisa
authors.initials: L
authors.lastname: Webber
authors.forename: Linna
authors.initials: L
authors.lastname: Ding
authors.forename: Lourdes P
authors.initials: LP
authors.lastname: Sejismundo
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mieras
authors.forename: David
authors.initials: D
authors.lastname: Weitzenkamp
authors.forename: David
authors.initials: D
authors.lastname: Ikle
authors.forename: Vicki
authors.initials: V
authors.lastname: Seyfert-Margolis
authors.forename: Mark
authors.initials: M
authors.lastname: Mueller
authors.forename: Paul
authors.initials: P
authors.lastname: Brunetta
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Allen
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: Duvuru
authors.initials: D
authors.lastname: Geetha
authors.forename: Karina A
authors.initials: KA
authors.lastname: Keogh
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Kissin
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.forename: Tobias
authors.initials: T
authors.lastname: Peikert
authors.forename: Coen
authors.initials: C
authors.lastname: Stegeman
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
mesh_terms: 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
chemical_list: 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