Ohkubo Naoaki, Nakayamada Shingo, Fukuyo Shunsuke, Miyazaki Yusuke, Inoue Yoshino, Tanaka Hiroaki, Todoroki Yasuyuki, Tanaka Yoshiya
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Int J Rheum Dis. 2025 Jun;28(6):e70292. doi: 10.1111/1756-185X.70292.
This study examined the efficacy and safety of Rituximab (RTX) treatment in connective tissue disease (CTD)-associated thrombocytopenic purpura (TTP) and thrombotic microangiopathy (TMA), using historical controls as comparators.
Patients who were admitted to our department from March 1, 2013 to March 31, 2021, and diagnosed with CTD-associated TTP/TMA refractory to plasma exchange were included in the study. A patient with treatment-resistant disease was treated with RTX in addition to high-dose glucocorticoid (GC) therapy (GC + RTX). As historical controls, we selected patients with CTD-associated TTP/TMA who were admitted to our center and treated with GC and immunosuppressants (IS) such as cyclophosphamide. The primary endpoint was the survival rate 52 weeks after the start of treatment.
Fifteen patients were enrolled in the study (GC + RTX). As a control group, 11 patients were enrolled in the same manner (GC + IS). There were no significant differences in age or sex or laboratory tests between the two groups. The primary endpoint of survival rate was significantly higher in the GC + RTX group than in the GC + IS group. In the immunophenotyping analysis before treatment, among all subsets of immune cells, only plasmocytes were significantly elevated in TTP patients compared to healthy controls. Plasmocytes correlated with serum markers, suggesting increased B cell differentiation, which was markedly decreased after RTX treatment.
In CTD-associated TTP/TMA, B cells may affect pathology, and adding RTX to plasma exchange and GC therapy may be worth considering.
本研究以历史对照为比较对象，考察了利妥昔单抗（RTX）治疗结缔组织病（CTD）相关血小板减少性紫癜（TTP）和血栓性微血管病（TMA）的疗效和安全性。
纳入2013年3月1日至2021年3月31日期间入住我科、诊断为CTD相关TTP/TMA且对血浆置换难治的患者。对一名治疗抵抗性疾病患者，除高剂量糖皮质激素（GC）治疗外，加用RTX治疗（GC + RTX）。作为历史对照，我们选择了入住我中心并接受GC和免疫抑制剂（IS）如环磷酰胺治疗的CTD相关TTP/TMA患者。主要终点是治疗开始后52周的生存率。
15例患者纳入本研究（GC + RTX）。作为对照组，11例患者以相同方式纳入（GC + IS）。两组在年龄、性别或实验室检查方面无显著差异。GC + RTX组的主要终点生存率显著高于GC + IS组。在治疗前的免疫表型分析中，在所有免疫细胞亚群中，与健康对照相比，TTP患者中仅浆细胞显著升高。浆细胞与血清标志物相关，提示B细胞分化增加，RTX治疗后明显降低。
在CTD相关TTP/TMA中，B细胞可能影响病理，在血浆置换和GC治疗中加用RTX可能值得考虑。
