B Cell Activation Biomarkers as Predictive Factors for the Response to Rituximab in Rheumatoid Arthritis
B Cell Activation Biomarkers as Predictive Factors for the Response to Rituximab in Rheumatoid Arthritis
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DOI：
10.1002/art.30233
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发表时间：
2011-04-01
影响因子：
--
通讯作者：
Mariette, Xavier
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文献类型：
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作者：
Sellam, Jeremie;Hendel-Chavez, Houria;Mariette, Xavier
Objective.检测血清B细胞标志物是否可以预测难治性类风湿关节炎（RA）患者对利妥昔单抗（一种B细胞耗竭单克隆抗体）的反应。这项利妥昔单抗再治疗剂量研究（SMART [eSsai MAbthera sur la dose de Re-Traitement]）涉及208例难治性RA患者。在第一个利妥昔单抗周期（第1天和第15天，1，000 mg）之前，评估B细胞活化的血清标志物（抗环瓜氨酸肽[抗CCP]抗体、类风湿因子[RF]、血清IgG、伊加和IgM水平、血清κ和λ游离轻链以及血清BAFF）。进行单变量和多变量分析以确定与欧洲抗风湿联盟（EULAR）24周反应相关的因素。有149名应答者（72%）。在多变量分析中，两个基线因素与24周时的EULAR应答相关：抗CCP抗体或RF的存在（比值比3.5 [95%置信区间1.6-7.6]）且血清IgG浓度高于正常值（优势比2.11 [95%可信区间1.02-4.33]），两者之间有协同作用（优势比6.0 [95%可信区间2.2-16.2]）。RF或抗CCP抗体的存在和IgG升高是2种简单的生物标志物，可在治疗前常规用于预测难治性RA患者对利妥昔单抗的反应。
Objective. To examine whether serum B cell markers can predict response to rituximab, a B cell-depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA).Methods. This rituximab re-treatment dose study (SMART [eSsai MAbthera sur la dose de Re-Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti-cyclic citrullinated peptide [anti-CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum kappa and lambda free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks.Results. There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti-CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6-7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02-4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2-16.2]).Conclusion. The presence of RF or anti-CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA.