Rituximab versus cyclophosphamide for ANCA-associated vasculitis with renal involvement.
Rituximab (RTX) is non-inferior to cyclophosphamide (CYC) followed by azathioprine (AZA) for remission-induction in severe ANCA-associated vasculitis (AAV), but renal outcomes are unknown. This is a post hoc analysis of patients enrolled in the Rituximab for ANCA-Associated Vasculitis (RAVE) Trial who had renal involvement (biopsy proven pauci-immune GN, red blood cell casts in the urine, and/or a rise in serum creatinine concentration attributed to vasculitis). Remission-induction regimens were RTX at 375 mg/m(2) × 4 or CYC at 2 mg/kg/d. CYC was replaced by AZA (2 mg/kg/d) after 3-6 months. Both groups received glucocorticoids. Complete remission (CR) was defined as Birmingham Vasculitis Activity Score/Wegener's Granulomatosis (BVAS/WG)=0 off prednisone. Fifty-two percent (102 of 197) of the patients had renal involvement at entry. Of these patients, 51 were randomized to RTX, and 51 to CYC/AZA. Mean eGFR was lower in the RTX group (41 versus 50 ml/min per 1.73 m(2); P=0.05); 61% and 75% of patients treated with RTX and 63% and 76% of patients treated with CYC/AZA achieved CR by 6 and 18 months, respectively. No differences in remission rates or increases in eGFR at 18 months were evident when analysis was stratified by ANCA type, AAV diagnosis (granulomatosis with polyangiitis versus microscopic polyangiitis), or new diagnosis (versus relapsing disease) at entry. There were no differences between treatment groups in relapses at 6, 12, or 18 months. No differences in adverse events were observed. In conclusion, patients with AAV and renal involvement respond similarly to remission induction with RTX plus glucocorticoids or CYC plus glucocorticoids.
Division of Nephrology and Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland;
Duvuru
D
Geetha
Division of Pulmonary and Critical Care Medicine and Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota;
Ulrich
U
Specks
Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts;
John H
JH
Stone
Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania;
Peter A
PA
Merkel
Division of Nephrology and Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland;
Philip
P
Seo
Rheumatology Division, Hospital for Special Surgery, New York, New York;
Robert
R
Spiera
Center for Vasculitis Care and Research, Cleveland Clinic Foundation, Cleveland, Ohio;
Carol A
CA
Langford
Center for Vasculitis Care and Research, Cleveland Clinic Foundation, Cleveland, Ohio;
Gary S
GS
Hoffman
Department of Rheumatology and Clinical Immunology University Medical Center, Groningen, The Netherlands;
Cees G M
CG
Kallenberg
Division of Rheumatology and Immunology, Duke University, Durham, North Carolina;
E William
EW
St Clair
Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama;
Barri J
BJ
Fessler
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland;
Linna
L
Ding
Immune Tolerance Network, San Francisco, CA;
Nadia K
NK
Tchao
Rho, Inc., Chapel Hill, North Carolina; and.
David
D
Ikle
Rho, Inc., Chapel Hill, North Carolina; and.
Brett
B
Jepson
Genentech, Inc., South San Francisco, California.
Paul
P
Brunetta
Division of Pulmonary and Critical Care Medicine and Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota; fervenza.fernando@mayo.edu.
Fernando C
FC
Fervenza
D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D017211:Treatment Failure
D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab; D003520:Cyclophosphamide; D001379:Azathioprine
ANCA; GN; vasculitis