RESEARCH - Treatment of refractory SLE with rituximab plus cyclophosphamide

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ls of the Rheumatic Diseases 2008;67:330-334

Copyright © 2008 BMJ Publishing Group Ltd & European League Against

Rheumatism

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EXTENDED REPORTS

Treatment of refractory SLE with rituximab plus cyclophosphamide:

clinical effects, serological changes, and predictors of response

T Jónsdóttir , I Gunnarsson , A Risselada , E W Henriksson , L

Klareskog , R F van Vollenhoven

1 Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden

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.

http://ard.bmj.com/cgi/content/abstract/67/3/330?etoc

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