利妥昔单抗治疗难治性结缔组织病七例

目的 评价利妥昔单抗治疗难治性结缔组织病的疗效和安全性.方法 对北京协和医院2005年1月至2008年2月收治的7例经大剂量激素联合多种免疫抑制剂和静脉人免疫球蛋白等治疗无效的难治性结缔组织病[系统性红斑狼疮(SLE)4例,原发性干燥综合征(pSS)、抗磷脂综合征和未分化结缔组织病各1例]患者予利妥昔单抗治疗,并评价利妥昔单抗治疗的疗效、安全性和预后.结果 患者中女性6例,男性1例,年龄21～58岁,病程3个月～20年.利妥昔单抗可有效改善包括顽固性重度血小板减少、自身免疫性溶血性贫血、狼疮肾炎等临床表现.4例患者在首剂利妥昔单抗应用后3周～5个月出现感染(包括带状疱疹1例次,单纯疱疹1例次,败血症1例次和肺部感染3例次),3例因严重肺部感染致呼吸衰竭死亡.结论 利妥昔单抗治疗难治性结缔组织病有效,但合并免疫抑制剂应用可能出现严重感染.

Anti-CD20 monoclonal antibody therapy in seven patients with refractory connective tissue disease

Objective To evaluate the safety and efficacy of anti -CD20 monoclonal antibody (rituximab) in treating refractory connective tissue disease (CTD) patients. Methods Seven inpatients with refractory CTD from Peking Union Medical College Hospital (PUMCH) including four cases of SLE, one for primary SS,one for undifferentiated CTD and one for antiphospholipid syndrome (APS), who had been admitted in recent 3 years (Jan 2005～Feb 2008) were treated with rituximab in combination with corticosteroid and immunosuppressive agents. Responses to treatment as well as outcomes were investigated. Results Six patients were female and one was male with the age ranged from 21 to 58 yr. Disease duration ranged from 3 months to 20 years. Rituximab resulted in significant improvement in clinical manifestations such as lupus nephritis, autoimmune hemolytic anemia and thrombocytopenia. Four patients developed secondary infection including lung infections,herpes and septicemia during B cell depletion, and three patients died of severe lung infections and respiratory failure. Conclusion Our study has shown promising efficacy of rituximab therapy in refractory CTD patients, though it increases the risk of fatal infections, especially when in combination with immunosuppressive agents.