title: Induction treatment of ANCA-associated vasculitis with a single dose of rituximab.
abstract: OBJECTIVE
  Rituximab is effective in inducing remission in ANCA-associated vasculitis (AAV), with randomized evidence to support its use as four infusions of 375 mg/m(2) (the conventional lymphoma dosing schedule). As B cell depletion (BCD) appears to occur very rapidly after the first dose, we questioned the need for repeat dosing and adopted a standard single-dose protocol of 375 mg/m(2) to treat active AAV.
  
  
  METHODS
  All consecutive cases with newly diagnosed or relapsing AAV for whom conventional immunosuppression was contraindicated or ineffective were enrolled. All were rituximab naive. Circulating CD19(+) B cells and clinical and serological markers of disease activity were recorded at regular intervals. Complete remission (CR) was defined as the absence of clinical features of AAV with a prednisolone dose <10 mg/day.
  
  
  RESULTS
  Nineteen patients were included, 17 (89%) with generalized disease and 2 (11%) with severe disease (creatinine level >500 μM). Eight (42%) were on additional immunosuppression at the time of rituximab treatment. Satisfactory BCD (<0.005 cells/μl) was achieved in 89% of patients after a median of 13 days. Three-month BCD probability was 89%. Median time to CR following a single dose of rituximab was 38 days and the 3-month probability of CR was 80%. Median time to B cell repopulation was 9.2 months and to disease relapse/redose was 27 months. Use of this single-dose protocol saved an estimated £4533/patient (US$7103; €5276) compared with a 4 × 375 mg/m(2) dosing schedule.
  
  
  CONCLUSIONS
  Our single-centre experience suggests that a single dose of rituximab of 375 mg/m(2) is a reasonable and more cost-effective therapy for inducing remission in patients with AAV.
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Tabitha
authors.initials: T
authors.lastname: Turner-Stokes
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Sandhu
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Pepper
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Stolagiewicz
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ashley
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Dinneen
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Howie
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Salama
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland.
authors.forename: Aine
authors.initials: A
authors.lastname: Burns
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, Department of Pathology, University College London, London, UK and Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland. mlittle@tcd.ie.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Little
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab; D011239:Prednisolone
keywords: ANCA; anti-CD20; lupus nephritis; monoclonal antibody; rituximab; vasculitis