Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center
Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center
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DOI：
10.1097/ccm.0b013e31822e9d66
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发表时间：
2012-01-01
影响因子：
8.8
通讯作者：
Coppo, Paul
中科院分区：
文献类型：
--
作者：
Froissart, Antoine;Buffet, Marc;Coppo, Paul
目的：评价利妥昔单抗对标准治疗反应不良的严重自身免疫性血栓性血小板减少性紫癜的疗效和安全性。设计：开放标签前瞻性研究。将幸存者的结果与53名单独或联合长春新碱治疗性血浆置换的历史幸存者的结果进行比较。环境：属于法国血栓性微血管病参考网络的医院。患者：22名接受强化血浆交换治疗后无反应或病情加重的成人。干预：加用利妥昔单抗治疗，15天内4次输注。测量和主要结果：1例患者在两次利妥昔单抗输注后死亡。在接受利妥昔单抗治疗的患者中，达到持久缓解的时间显着缩短（p = .03），尽管与对照组相比，实现持久缓解所需的血浆量没有显着差异。所有21名幸存者的血小板计数在35天内恢复，而历史对照组只有78% （p < 0.02）。在接受利妥昔单抗治疗的患者中，没有人在一年内复发，但后来有三人复发。在接受利妥昔单抗治疗的患者中，产生了快速而深刻的外周b细胞耗损，持续9个月，并与较高的a崩解素和金属蛋白酶与血小板spondin-13活性以及较低的抗a崩解素和金属蛋白酶与血小板spondin-13抗体滴度相关。12个月后，这些差异不再显著。没有发生严重的副作用。结论：严重血小板减少性紫癜的成人患者对治疗性血浆置换反应较差，接受利妥昔单抗治疗的总治疗时间较短，1年复发率低于历史对照组。（急救医疗2012；40:104-111）
Objective: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura.Design: Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine.Setting: Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France.Patients: Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange.Intervention: Add-on rituximab therapy, four infusions over 15 days.Measurements and Main Results: One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred.Conclusions: Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls. (Crit Care Med 2012; 40:104-111)