title: Long-term efficacy and safety of rituximab in refractory and relapsing systemic lupus erythematosus.
abstract: BACKGROUND
  Systemic lupus erythematosus is a relapsing autoimmune disease. Conventional therapy increases the risk of infection and malignancies; furthermore, a minority of patients suffer from refractory disease. B-cell depletion with the chimeric +AFw-anti-CD20 monoclonal antibody, rituximab, is an alternative therapy for relapsing and refractory systemic lupus erythematosus. We sought to assess the long-term efficacy and safety of rituximab in this patient subgroup.
  
  
  METHODS
  Thirty-one sequential patients with relapsing or refractory systemic lupus erythematosus, 11 of whom had active lupus nephritis, received rituximab [either 375 mg/m(2)/week × 4 (n = 16) or 1000 mg × 2 (n = 15)]. The median follow-up was 30 months.
  
  
  RESULTS
  Thirty of 31 (97%) patients had depleted peripheral B cells. Twenty-seven of 31 (87%) patients achieved remission (17 complete, 10 partial). Renal response occurred in 10/11 patients (4 complete, 6 partial) with active glomerulonephritis. Clinical improvement was reflected by reductions of disease activity, proteinuria and daily prednisolone dose. Eighteen of 27 (67%) patients relapsed after a median of 11 months. Relapses occurred on or after the return of circulating B cells in 10 but in the absence of B-cell return in 8. Re-treatment with rituximab was effective. Infusion reactions were common (18/31; 58%), and infections occurred in 8/31 (26%) patients.
  
  
  CONCLUSIONS
  Rituximab had a high rate of efficacy in relapsing or refractory systemic lupus erythematosus with or without renal involvement. Although relapse was common, it responded to re-treatment. The contribution of rituximab to infection risk was uncertain in view of the complex disease course and concomitant therapy of the patients studied.
authors.affiliation: Vasculitis and Lupus Clinic, Renal Unit, Addenbrooke's Hospital, Cambridge University, Hills Road, UK. faustac@libero.it
authors.forename: Fausta
authors.initials: F
authors.lastname: Catapano
authors.forename: Afzal N
authors.initials: AN
authors.lastname: Chaudhry
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Jones
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.forename: David W
authors.initials: DW
authors.lastname: Jayne
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D003176:Complement C3 / Q000032:analysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D012008:Recurrence; D000069283:Rituximab
chemical_list: D000974:Antibodies, Antinuclear; D058846:Antibodies, Monoclonal, Murine-Derived; D003176:Complement C3; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000069283:Rituximab