Haemostasis Research Unit, University College London Department of Haematology, London, UK.
J Thromb Haemost. 2010 Jun;8(6):1201-8. doi: 10.1111/j.1538-7836.2010.03818.x. Epub 2010 Feb 19.
Increasingly, patients with acute, idiopathic, antibody mediated thrombotic thrombocytopenic purpura (TTP) are being treated with rituximab to achieve a durable remission, however, there is the potential that it is removed by plasma exchange (PEX).
To look at the pharmacokinetics and pharmacodynamics of rituximab in patients with acute idiopathic TTP undergoing PEX.
Patients who received rituximab for acute idiopathic TTP (group 1, n = 30) and a control group (group 2, n = 3) of TTP patients in remission receiving rituximab electively as maintenance were included. Rituximab levels were measured before/after each infusion, before/after PEX and in follow-up. ADAMTS-13 activity, anti-ADAMTS-13 IgG and CD19% were measured to assess response.
The median number of PEX to remission after rituximab was 10 (range 4-25). In group 1 there was no significant incremental rise in the peak serum rituximab level until dose 4. Trough levels were lower in patients who had had PEX since their last rituximab infusion. In the control group, there was an incremental rise in the peak serum rituximab level and all patients had detectable trough levels. The median fall in rituximab per PEX was 65%. All patients achieved CD19 < 1%. In group 1, the median time to undetectable rituximab was 5 months (range 0-12 months) and to B cell return was 7 months (range 3-24 months). ADAMTS-13 increased and anti-ADAMTS-13 fell after therapy. There were three deaths and two relapses in group 1. Relapse was not temporally related to B cell return.
越来越多的急性、特发性、抗体介导的血栓性血小板减少性紫癜（TTP）患者接受利妥昔单抗治疗以实现持久缓解，但它有可能被血浆置换（PEX）清除。
观察接受 PEX 的急性特发性 TTP 患者利妥昔单抗的药代动力学和药效动力学。
纳入了接受利妥昔单抗治疗急性特发性 TTP 的患者（第 1 组，n = 30）和作为维持治疗选择接受利妥昔单抗的缓解期 TTP 患者的对照组（第 2 组，n = 3）。在每次输注前后、PEX 前后和随访时测量利妥昔单抗水平。测量 ADAMTS-13 活性、抗 ADAMTS-13 IgG 和 CD19%以评估反应。
利妥昔单抗后达到缓解的 PEX 中位数为 10 次（范围 4-25）。在第 1 组中，直到第 4 次剂量才出现血清利妥昔单抗峰值水平的显著递增。与最后一次利妥昔单抗输注后进行 PEX 的患者相比，患者的低谷水平较低。在对照组中，血清利妥昔单抗峰值水平呈递增趋势，所有患者均有可检测的低谷水平。每次 PEX 降低利妥昔单抗的中位数为 65%。所有患者均达到 CD19 < 1%。在第 1 组中，不可检测到利妥昔单抗的中位时间为 5 个月（范围 0-12 个月），B 细胞恢复的中位时间为 7 个月（范围 3-24 个月）。治疗后 ADAMTS-13 增加，抗 ADAMTS-13 下降。第 1 组中有 3 例死亡和 2 例复发。复发与 B 细胞恢复无时间关系。
