title: Effect of Continuous B Cell Depletion With Rituximab on Pathogenic Autoantibodies and Total IgG Levels in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
abstract: To evaluate the effect of rituximab on pathogenic autoantibodies and total Ig levels, and to identify serious adverse events in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with continuous B cell depletion.
  
  
  
  We conducted a retrospective analysis of 239 patients with AAV treated with rituximab-induced continuous B cell depletion. Two treatment cohorts were analyzed: an induction group (n = 52) and a maintenance group (n = 237). Changes in ANCA titers and total Ig levels over time were evaluated using mixed-effects models. Risk factors for serious infections during maintenance treatment were evaluated using Poisson regression.
  
  
  
  During induction, IgG levels fell at a mean rate of 6% per month (95% confidence interval [95% CI] 4, 8%), while ANCA levels declined at a mean rate of 47% per month (95% CI 42, 52%) and 48% per month (95% CI 42, 54%) for patients with antimyeloperoxidase (anti-MPO) antibodies and those with anti-proteinase 3 (anti-PR3) antibodies, respectively. During maintenance treatment, with a median duration of 2.4 years (interquartile range 1.5, 4.0 years), IgG levels declined a mean of 0.6% per year (95% CI -0.2, 1.4%). New significant hypogammaglobulinemia (IgG level of <400 mg/dl) during maintenance treatment occurred in 4.6% of the patients, all of whom were in the lowest baseline IgG quartile. Serious infections during maintenance therapy occurred at a rate of 0.85 per 10 patient-years (95% CI 0.66, 1.1) and were independently associated with an IgG level of <400 mg/dl.
  
  
  
  B cell-targeted therapy causes a preferential decline in ANCA titers relative to total IgG levels. Despite prolonged maintenance therapy with rituximab, IgG levels remain essentially constant. Serious infections were rare.
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Cortazar
authors.affiliation: University of North Carolina Kidney Center, Chapel Hill.
authors.forename: William F
authors.initials: WF
authors.lastname: Pendergraft
authors.affiliation: University of North Carolina Kidney Center, Chapel Hill.
authors.forename: Julia
authors.initials: J
authors.lastname: Wenger
authors.affiliation: Baylor University Medical Center at Dallas, Dallas, Texas.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Owens
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: Karen
authors.initials: K
authors.lastname: Laliberte
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: John L
authors.initials: JL
authors.lastname: Niles
mesh_terms: D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced; D007239:Infections / Q000209:etiology / Q000276:immunology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology*; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab / Q000627:therapeutic use*
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D000069283:Rituximab; D009195:Peroxidase; D053146:Myeloblastin