总淋巴细胞计数>2910/μl或浆母细胞>2.85%的RA患者用利妥昔单抗疗效不佳

作者：Stradner MH，et al.

翻译：北医三院安文成

摘要：目的：虽然在类风湿关节炎中利妥昔单抗清除B细胞是一种有效的治疗策略，但仍有三分之一的患者不能达到缓解或低疾病活动状态。因此，明确患者是否能在利妥昔单抗的治疗中获益是十分有必要的。在这项研究中，我们主要探讨在利妥昔单抗临床治疗的疗效预测中，淋巴细胞亚型的作用是否优于B细胞。

方法：研究纳入了初次使用利妥昔单抗治疗的类风湿关节炎患者，采集基线及治疗24周时的血常规、淋巴细胞亚群（流式细胞术），完成数据采集的共44人。在第24周以欧洲抗风湿联盟治疗（EULAR）反应和低疾病活动状态（定义为28个关节的评分(DAS28)≤3.2）进行评估，分别应用线性回归、受试者工作特征曲线对淋巴细胞亚群的预测作用进行分析。

结果：有EULAR反应患者的基线总淋巴细胞计数、T细胞计数和CD4?+?T水平均较低，但这些指标却不能预测达到低疾病活动状态的情况，相反，基线总淋巴细胞计数>2910/μl或浆母细胞>2.85%的患者预示在利妥昔单抗治疗24周后的DAS28评分偏高，不能达到低疾病活动状态的敏感性达93.3%，而特异性较低，为44.8%。

结论：总淋巴细胞数和浆母细胞比例共同预测类风湿关节炎患者在利妥昔单抗疗效不佳。

附原文:BACKGROUND: Although B cell depletion with rituximab (RTX) is an effective treatment strategy in rheumatoid arthritis (RA), one third of patients do not achieve remission or low disease activity (LDA). Thus, identifying patients who will benefit from RTX is highly desirable. In the present study we investigated whether lymphocyte subsets other than B cells are predictors of a clinical response to RTX treatment.METHODS: Patients with RA who were receiving RTX for the first time were included in an observatory registry. Clinical assessments, complete blood count and flow cytometry of lymphocyte subsets were obtained at baseline and at week 24 after RTX. Complete data were available for 44 patients. Logistic regression and receiver operating characteristic curve analyses were computed to analyze the predictive value of lymphocyte subsets for European League Against Rheumatism (EULAR) response and LDA (defined as disease activity score in 28 joints (DAS28) ≤3.2) at week 24.RESULTS: EULAR responders had lower total lymphocyte counts (LC), T cells and CD4?+?T cells at baseline. Although these parameters were independent predictors of EULAR response they failed in determining who would reach LDA. In contrast, LC >2910/μl or plasmablast frequency >2.85 % at baseline predicted a significantly higher DAS28 at week 24 after RTX and identified patients not achieving LDA at week 24 with sensitivity of 93.3 % and specificity of 44.8 %.CONCLUSIONS:A combination of LC and plasmablast frequency identifies patients with RA who will not benefit from RTX with high probability.

引自：Stradner MH, Dejaco C, Brickmann K, et al. A combination of cellular biomarkers predicts failure to respond to rituximab in rheumatoid arthritis: a 24-week observational study. Arthritis Res Ther. 2016 Aug 24;18:190