Rituximab versus cyclophosphamide for ANCA-associated vasculitis with renal involvement.

Abstract

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.

• Authors: Duvuru Geetha, Ulrich Specks, John H Stone, Peter A Merkel, Philip Seo, Robert Spiera, Carol A Langford, Gary S Hoffman, Cees G M Kallenberg, E William St Clair, Barri J Fessler, Linna Ding, Nadia K Tchao, David Ikle, Brett Jepson, Paul Brunetta, Fernando C Fervenza, Rituximab for ANCA-Associated Vasculitis Immune Tolerance Network Research Group
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 26 Issue 4 Pg. 976-85 (Apr 2015) ISSN: 1533-3450 [Electronic] United States
• PMID: 25381429 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by the American Society of Nephrology.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunologic Factors
• Rituximab
• Cyclophosphamide
• Azathioprine

Topics

• Adult
• Aged
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy)
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Azathioprine (therapeutic use)
• Cyclophosphamide (therapeutic use)
• Female
• Glomerulonephritis (drug therapy)
• Humans
• Immunologic Factors (therapeutic use)
• Kidney Function Tests
• Male
• Middle Aged
• Recurrence
• Remission Induction
• Rituximab
• Treatment Failure