title: Single-dose rituximab in refractory lupus nephritis.
abstract: BACKGROUND
  Off-label use of rituximab in lupus nephritis is reported to be beneficial. While the optimal dose is unknown, the regimen of four intravenous doses of 375 mg/m(2) is commonly employed, despite expense and potential side-effects.
  
  
  OBJECTIVE
  To investigate the response to single-dose rituximab, added to standard corticosteroids plus additional immunosuppressive agent, in refractory lupus nephritis.
  
  
  METHODS
  Consecutive consenting patients with refractory lupus nephritis despite steroids plus either cyclophosphamide, mycophenolate or azathioprine were enrolled in this ethics-approved, open-label, prospective study. After baseline assessment, patients received one intravenous infusion of 375 mg/m(2) rituximab. Clinical, biochemical and serological (DsDNA, complement) responses to this dose were analysed. Complete renal response (CR) was defined as normalisation of creatinine, albumin, proteinuria and urinary RBCs and partial response (PR) as ≥50% improvement in at least one parameter, without deterioration in others. B-cell depletion was defined as peripheral CD19 lymphocyte count ≤0.05 × 10(9) /L.
  
  
  RESULTS
  Fourteen patients were enrolled in the study. All were B-cell-depleted until 8 months post-dose. Eleven patients (79%) responded (2CR, 9PR) at a median time of 5 months, with a 6-month probability of renal response of 43%. Five patients (45%) relapsed at a median time of 17 months. DsDNA titres decreased in 69%. Side-effects were minimal.
  
  
  CONCLUSIONS
  Single-dose rituximab is effective in relapsed/refractory lupus nephritis. Longevity of B-cell depletion with single-dose rituximab is similar to that of four doses with potentially fewer side-effects.
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Kotagiri
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.|Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Hughes
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.|Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Becker
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.|Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Nicholls
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D001315:Australia; D001379:Azathioprine / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008181:Lupus Nephritis / Q000188:drug therapy*; D018655:Lymphocyte Count; D008297:Male; D009173:Mycophenolic Acid / Q000627:therapeutic use; D056687:Off-Label Use; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine
keywords: SLE; auto-immune glomerulonephritis; refractory lupus nephritis; refractory vasculitis; rituximab