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Ann Rheum Dis 67:330-334 doi:10.1136/ard.2007.079095
  • Extended report

Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response

  1. T Jónsdóttir,
  2. I Gunnarsson,
  3. A Risselada,
  4. E W Henriksson,
  5. L Klareskog,
  6. R F van Vollenhoven
  1. 1
    Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  1. Dr Ronald F van Vollenhoven, Department of Rheumatology, D2:01, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden; ronald.van.vollenhoven{at}ki.se
  • Accepted 2 September 2007
  • Published Online First 7 September 2007

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.

Footnotes

  • TJ and IG contributed equally to the study.

  • Funding: Supported by a grant from King Gustaf V’s 80th Birthday Fund and funds from the Karolinska Institute and the Swedish fund for the Renal Research. The fee to register the study with the Swedish Medical Product Agency was paid for by Roche AB, Stockholm, Sweden.

  • Competing interests: None declared

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