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

被引:117
作者
Jonsdottir, T. [1 ]
Gunnarsson, I. [1 ]
Risselada, A. [1 ]
Henriksson, E. W. [1 ]
Klareskog, L. [1 ]
van Vollenhoven, R. F. [1 ]
机构
[1] Karolinska Univ Hosp, Dept Rheumatol, S-17176 Stockholm, Sweden
关键词
D O I
10.1136/ard.2007.079095
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 down-regulation 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.
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页码:330 / 334
页数:5
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