title: Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response.
abstract: OBJECTIVE
  To evaluate efficacy, serological responses, and predictors of response in patients with severe and refractory systemic lupus erythematosus (SLE) treated with rituximab plus cyclophosphamide.
  
  
  METHODS
  16 patients entered a treatment protocol using rituximab plus cyclophosphamide. Disease activity was assessed by the SLE disease activity index (SLEDAI) and by the British Isles Lupus Assessment Group (BILAG) index.
  
  
  RESULTS
  At six months follow up, mean SLEDAI values decreased significantly from (mean (SD)) 12.1 (2.2) to 4.7 (1.1). Clinical improvement (50% reduction in SLEDAI) occurred in all but three patients. All but one patient responded according to BILAG. Remission defined as SLEDAI <3 was achieved in nine of 16 patients. Isotype analysis of anti-dsDNA antibodies revealed preferential decreases of IgG and IgA, but not IgM. Higher absolute numbers of CD19+ cells at baseline were correlated with shorter depletion time (r = -0.6).
  
  
  CONCLUSIONS
  The majority of patients improved following rituximab plus cyclophosphamide. The differential downregulation of anti-DNA of the IgG and IgA but not the IgM isotypes supports the hypothesis that cells producing pathogenic autoantibodies are preferentially targeted by the treatment. The fact that greater absolute numbers of CD19+ cells at baseline predict a less impressive clinical and serological response suggests that more flexible dosing could be advantageous.
authors.affiliation: Department of Rheumatology, The Karolinska University Hospital, The Karolinska Institutet, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Jónsdóttir
authors.forename: I
authors.initials: I
authors.lastname: Gunnarsson
authors.forename: A
authors.initials: A
authors.lastname: Risselada
authors.forename: E W
authors.initials: EW
authors.lastname: Henriksson
authors.forename: L
authors.initials: L
authors.lastname: Klareskog
authors.forename: R F
authors.initials: RF
authors.lastname: van Vollenhoven
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000097:blood; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome