Jónsdóttir T, Gunnarsson I, Risselada A, Henriksson E W, Klareskog L, van Vollenhoven R F
Department of Rheumatology, The Karolinska University Hospital, The Karolinska Institutet, Stockholm, Sweden.
Ann Rheum Dis. 2008 Mar;67(3):330-4. doi: 10.1136/ard.2007.079095. Epub 2007 Sep 7.
To evaluate efficacy, serological responses, and predictors of response in patients with severe and refractory systemic lupus erythematosus (SLE) treated with rituximab plus cyclophosphamide.
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.
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).
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.
评估利妥昔单抗联合环磷酰胺治疗重症难治性系统性红斑狼疮（SLE）患者的疗效、血清学反应及反应预测因素。
16例患者进入利妥昔单抗联合环磷酰胺的治疗方案。采用SLE疾病活动指数（SLEDAI）和英伦三岛狼疮评估组（BILAG）指数评估疾病活动度。
随访6个月时，SLEDAI均值从（均值（标准差））12.1（2.2）显著降至4.7（1.1）。除3例患者外，所有患者临床均有改善（SLEDAI降低50%）。除1例患者外，所有患者根据BILAG标准均有反应。16例患者中有9例实现了SLEDAI<3的缓解。抗双链DNA抗体的亚型分析显示IgG和IgA优先降低，而IgM未降低。基线时CD19+细胞的绝对数量越高，与耗竭时间越短相关（r = -0.6）。
大多数患者在接受利妥昔单抗联合环磷酰胺治疗后病情改善。IgG和IgA而非IgM亚型的抗DNA差异下调支持了以下假设：产生致病性自身抗体的细胞是该治疗的优先靶点。基线时CD19+细胞绝对数量越多，临床和血清学反应越不显著，这一事实表明更灵活的给药方案可能更具优势。
