Rituximab Versus Cyclophosphamide for ANCA-Associated... : Journal of the American Society of Nephrology (original) (raw)

Clinical Research

Rituximab Versus Cyclophosphamide for ANCA-Associated Vasculitis with Renal Involvement

Geetha, Duvuru*; Specks, Ulrich†; Stone, John H.‡; Merkel, Peter A.§‖; Seo, Philip*; Spiera, Robert¶; Langford, Carol A.**; Hoffman, Gary S.**; Kallenberg, Cees G.M.††; St. Clair, E. William‡‡; Fessler, Barri J.§§; Ding, Linna‖‖; Tchao, Nadia K.¶¶; Ikle, David***; Jepson, Brett***; Brunetta, Paul†††; Fervenza, Fernando C.†

*Division of Nephrology and Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland;

†Division of Pulmonary and Critical Care Medicine and Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota;

‡Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts;

§‖Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania;

¶Rheumatology Division, Hospital for Special Surgery, New York, New York;

**Center for Vasculitis Care and Research, Cleveland Clinic Foundation, Cleveland, Ohio;

††Department of Rheumatology and Clinical Immunology University Medical Center, Groningen, The Netherlands;

‡‡Division of Rheumatology and Immunology, Duke University, Durham, North Carolina;

§§Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama;

‖‖National Institute of Allergy and Infectious Diseases, Bethesda, Maryland;

¶¶Immune Tolerance Network, San Francisco, CA;

***Rho, Inc., Chapel Hill, North Carolina; and

†††Genentech, Inc., South San Francisco, California

Correspondence: Dr. Fernando C. Fervenza, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55901. Email: [email protected]

Received January 11, 2014

Accepted July 14, 2014

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/m2 × 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 m2; _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.