Vital E M, Dass S, Rawstron A C, Buch M H, Goëb V, Henshaw K, Ponchel F, Emery P
University of Leeds, Chapel Allerton Hospital and Leeds Teaching Hospitals National Health Service Trust, Leeds, UK.
Arthritis Rheum. 2010 May;62(5):1273-9. doi: 10.1002/art.27359.
A proportion of patients with rheumatoid arthritis (RA) have disease that fails to respond to an initial cycle of rituximab. Using highly sensitive flow cytometry (HSFC), it has been shown that most patients who do not exhibit a response, as measured using the European League Against Rheumatism (EULAR) criteria, have persistent circulating B cell levels at week 2 after initial treatment with rituximab. This study was undertaken to examine whether an additional cycle of rituximab would improve B cell depletion and clinical response in patients whose disease did not respond to the initial cycle.
Patients with RA (n = 158) were treated with a first cycle of rituximab (2 infusions of 1 gm each). Clinical responses were assessed using EULAR criteria, and patients were categorized as either first-cycle responders or first-cycle nonresponders. Baseline characteristics of first-cycle nonresponders (n = 38) and first-cycle responders (n = 65) with complete data were compared. First-cycle nonresponders (n = 25) were treated with a second cycle of rituximab at least 6 months after the first cycle. HSFC was performed at baseline, immediately prior to the second infusion (week 2), 1 month after the second infusion (week 6), and then every 3 months for each cycle of rituximab. Complete B cell depletion was defined as being <0.0001 x 10(9) cells/liter.
At baseline, the number of preplasma cells was significantly higher in first-cycle nonresponders than in first-cycle responders (P = 0.003). Following the first infusion of the first cycle of rituximab, only 9% of first-cycle nonresponders (3 of 34) exhibited complete depletion of B-lineage cells, compared with 37% of first-cycle responders (22 of 59) (P = 0.007). Following the first infusion of the second cycle of rituximab, 38% of first-cycle nonresponders exhibited complete depletion. Twenty-six weeks after the second cycle, there was a significant improvement in the Disease Activity Score in 28 joints, with 72% of patients exhibiting a EULAR response.
RA patients whose disease did not respond to an initial cycle of rituximab have higher circulating preplasma cell numbers at baseline and incomplete depletion. Our findings indicate that an additional cycle of rituximab administered prior to total B cell repopulation enhances B cell depletion and clinical responses.
一部分类风湿关节炎（RA）患者对利妥昔单抗的初始治疗周期无反应。使用高灵敏度流式细胞术（HSFC）已表明，大多数未达到反应（根据欧洲抗风湿病联盟（EULAR）标准衡量）的患者在利妥昔单抗初始治疗后第2周时循环B细胞水平持续存在。本研究旨在探讨额外一个周期的利妥昔单抗是否会改善疾病对初始周期无反应患者的B细胞清除及临床反应。
158例RA患者接受利妥昔单抗的第一个周期治疗（每次输注1克，共2次）。使用EULAR标准评估临床反应，患者被分类为第一个周期有反应者或第一个周期无反应者。比较有完整数据的第一个周期无反应者（n = 38）和第一个周期有反应者（n = 65）的基线特征。第一个周期无反应者（n = 25）在第一个周期至少6个月后接受第二个周期的利妥昔单抗治疗。在基线、第二次输注前即刻（第2周）、第二次输注后1个月（第6周）以及之后每3个月对每个利妥昔单抗周期进行HSFC检测。完全B细胞清除定义为<0.0001×10⁹细胞/升。
在基线时，第一个周期无反应者的前浆细胞数量显著高于第一个周期有反应者（P = 0.003）。在利妥昔单抗第一个周期的第一次输注后，只有9%的第一个周期无反应者（34例中的3例）表现出B系细胞完全清除，而第一个周期有反应者为37%（59例中的22例）（P = 0.007）。在利妥昔单抗第二个周期的第一次输注后，38%的第一个周期无反应者表现出完全清除。第二个周期后26周，28个关节的疾病活动评分有显著改善，72%的患者表现出EULAR反应。
疾病对利妥昔单抗初始周期无反应的RA患者在基线时循环前浆细胞数量更高且清除不完全。我们的研究结果表明，在总B细胞重新增殖之前给予额外一个周期的利妥昔单抗可增强B细胞清除及临床反应。
