title: Rituximab as an immunosuppressant in antineutrophil cytoplasmic antibody-associated vasculitis.
abstract: BACKGROUND
  Rituximab has been used in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) since 2003. Our objective was to describe outcomes and adverse events following rituximab since that time in an inception cohort.
  
  
  METHODS
  Patients with AAV (diagnosed 1991-2012) who received rituximab (n = 120) were evaluated and incidence per person-year (PPY) with 95% confidence interval was calculated for relapse and infections. Time to remission and relapse by number of rituximab infusions given per treatment course (≤2 versus >2) and by ever having been exposed to cyclophosphamide were compared using Kaplan-Meier curves. Rituximab-treated patients were characterized in comparison with AAV patients treated with cyclophosphamide but not exposed to rituximab (n = 351) using Fisher's exact or rank tests.
  
  
  RESULTS
  Rituximab resulted in 86% achieving remission and 41% having a subsequent relapse in a median of 19 months (range 9-29). Time to remission and relapse were similar between rituximab infusion courses (≤2 versus >2; remission P = 0.86 and relapse P = 0.78, respectively). Incidence of relapse was 0.22 PPY (0.14, 0.31) and of severe infection was 0.12 PPY (0.08, 0.24). Time to relapse was shorter in those never exposed to cyclophosphamide (n = 20): 50% by 8 months versus 50% by 24 and 30 months for those with prior or concurrent exposure to cyclophosphamide (n = 100). Compared with those who never received rituximab, rituximab-treated patients were younger (P < 0.001), more likely to have granulomatosis with polyangiitis (P = 0.001) and had more upper airway (P = 0.01) and less kidney involvement (P = 0.007).
  
  
  CONCLUSIONS
  Rituximab is beneficial when prescribed outside of a trial setting. Response to treatment and relapse is similar regardless of infusion number. Rituximab without cyclophosphamide may result in a shorter time to relapse supporting combination of these therapies.
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: JulieAnne G
authors: JG
authors: McGregor
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Susan L
authors: SL
authors: Hogan
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Duke University Medical Center, Durham, NC, USA.
authors: Elizabeth S
authors: ES
authors: Kotzen
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Caroline J
authors: CJ
authors: Poulton
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Yichun
authors: Y
authors: Hu
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Hospital Universitario-UANL Monterrey, Nuevo Leon, Mexico.
authors: Roberto
authors: R
authors: Negrete-Lopez
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Medical College of Virginia, Richmond, VA, USA.
authors: Jason M
authors: JM
authors: Kidd
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Suzanne L
authors: SL
authors: Katsanos
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Donna O
authors: DO
authors: Bunch
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Patrick H
authors: PH
authors: Nachman
authors: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Ronald J
authors: RJ
authors: Falk
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000401:mortality; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide
keywords: ANCA; glomerulonephritis; immunosuppression; outcomes; relapse