Marta Casal Moura1, Maria V Irazabal2, Alfonso Eirin2, Ladan Zand2, Sanjeev Sethi3, Bijan J Borah4,5, Jeffrey L Winters6, James P Moriarty4,5, Rodrigo Cartin-Ceba7, Alvise Berti1, Misbah Baqir1, Gwen E Thompson1, Ashima Makol8, Kenneth J Warrington8, Viengneesee Thao4,5, Ulrich Specks9, Fernando C Fervenza10. 1. Division of Pulmonary and Critical Care, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. 2. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. 3. Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. 4. Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota. 5. Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. 6. Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. 7. Division of Pulmonary Medicine, Department of Medicine, Mayo Clinic Arizona, Phoenix, Arizona. 8. Division of Rheumatology, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. 9. Division of Pulmonary and Critical Care, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota specks.ulrich@mayo.edu fervenza.fernando@mayo.edu. 10. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota specks.ulrich@mayo.edu fervenza.fernando@mayo.edu.
Abstract
BACKGROUND: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX). METHODS: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. RESULTS: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC (n=161) or RTX (n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330). CONCLUSIONS: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.
BACKGROUND: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX). METHODS: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. RESULTS: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC (n=161) or RTX (n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330). CONCLUSIONS: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.
Authors: Shivani Shah; Zdenka Hruskova; Marten Segelmark; Matthew D Morgan; Jonathan Hogan; Steven K Lee; Jessica Dale; Lorraine Harper; Vladimir Tesar; David R W Jayne; Duvuru Geetha Journal: Am J Nephrol Date: 2015-06-02 Impact factor: 3.754
Authors: P A Merkel; D D Cuthbertson; B Hellmich; G S Hoffman; D R W Jayne; C G M Kallenberg; J P Krischer; R Luqmani; A D Mahr; E L Matteson; U Specks; J H Stone Journal: Ann Rheum Dis Date: 2008-07-29 Impact factor: 19.103
Authors: G S Hoffman; G S Kerr; R Y Leavitt; C W Hallahan; R S Lebovics; W D Travis; M Rottem; A S Fauci Journal: Ann Intern Med Date: 1992-03-15 Impact factor: 25.391
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391