Treatment of refractory SLE with rituximab plus cyclophosphamide:: clinical effects, serological changes, and predictors of response
Treatment of refractory SLE with rituximab plus cyclophosphamide:: clinical effects, serological changes, and predictors of response
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DOI：
10.1136/ard.2007.079095
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发表时间：
2008-03-01
影响因子：
27.4
通讯作者：
van Vollenhoven, R. F.
中科院分区：
文献类型：
--
作者：
Jonsdottir, T.;Gunnarsson, I.;van Vollenhoven, R. F.
目的：评估利妥昔单抗联合环磷酰胺治疗严重难治性系统性红斑狼疮 (SLE) 患者的疗效、血清学反应和反应预测因素。方法：16 名患者进入了利妥昔单抗联合环磷酰胺的治疗方案。疾病活动度通过 SLE 疾病活动指数 (SLEDAI) 和不列颠群岛狼疮评估组 (BILAG) 指数进行评估。结果：随访 6 个月时，平均 SLEDAI 值从（平均值（SD））12.1（2.2）显着下降至 4.7（1.1）。除三名患者外，所有患者均出现临床改善（SLEDAI 降低 50%）。根据 BILAG，除一名患者外，所有患者均有反应。 16 名患者中有 9 名实现了缓解（定义为 SLEDAI < 3）。抗 dsDNA 抗体的同种型分析显示 IgG 和 IgA 优先减少，但 IgM 不减少。基线时 CD19+ 细胞绝对数较高与较短的耗尽时间相关 (r=-0.6)。 结论：大多数患者在利妥昔单抗加环磷酰胺治疗后病情有所改善。 IgG 和 IgA 的抗 DNA 差异性下调，但 IgM 同种型则不然，这支持了这样的假设：产生致病性自身抗体的细胞优先成为治疗的目标。事实上，基线时 CD19+ 细胞的绝对数量越大，预示临床和血清学反应就不那么令人印象深刻，这表明更灵活的剂量可能是有利的。
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.