A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis
A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis
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DOI：
10.1182/blood-2011-08-371138
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发表时间：
2011-12-08
期刊：
影响因子：
20.3
通讯作者：
Margolin, David H.
中科院分区：
文献类型：
--
作者：
Cuker, Adam;Coles, Alasdair J.;Margolin, David H.
在一项每年一次的Alemtuzumab治疗复发缓解型多发性硬化症的II期临床试验中，216例患者中有6例（2.8%）发生了免疫性血小板减少症（ITP）。平均随访4.5年，ITP的发生率为6.2（95%置信区间，2.3-13.3）/1000人-年。从初始和末次Alemtuzumab暴露至ITP诊断的中位时间分别为24.5和10.5个月。5例患者发生重度血小板减少症。4例有症状，包括索引病例中的致死性颅内出血。4例患者接受标准一线ITP治疗，所有患者均在1周内对治疗有反应。末次随访时，所有5例存活患者均达到完全缓解，并保持完全缓解，无需继续接受ITP治疗，中位持续时间为34个月。在指示病例出现后实施的ITP早期检测监测计划，在发生严重出血性发病或死亡之前确定了所有5例后续病例。总之，我们描述了一种与Alemtuzumab治疗相关的独特形式的ITP，其特征为药物暴露后延迟出现、对传统ITP治疗的反应性和缓解时间延长。临床医生应保持高度警惕，并考虑对接受该药物治疗的患者进行ITP的常规监测。该试验在www.clinicaltrials.gov上注册为#NCT00050778。（血。2011;118（24）：6299-6305）
In a phase 2 clinical trial of annual alemtuzumab for treatment of relapsing-remitting multiple sclerosis, 6 of 216 patients (2.8%) developed immune thrombocytopenia (ITP). Over mean follow-up of 4.5 years, the incidence rate of ITP was 6.2 (95% confidence interval, 2.3-13.3) per 1000 person-years. Median times from initial and last alemtuzumab exposure to ITP diagnosis were 24.5 and 10.5 months, respectively. Five patients developed severe thrombocytopenia. Four were symptomatic, including fatal intracranial hemorrhage in the index case. Four patients received standard first-line ITP therapy, all of whom responded to treatment within 1 week. All 5 surviving patients achieved complete remission and remained in complete remission without need for ongoing ITP therapy for a median duration of 34 months at last follow-up. A monitoring plan for the early detection of ITP, implemented after presentation of the index case, identified all 5 subsequent cases before serious hemorrhagic morbidity or mortality occurred. In conclusion, we describe a distinctive form of ITP associated with alemtuzumab treatment characterized by delayed presentation after drug exposure, responsiveness to conventional ITP therapies, and prolonged remission. Clinicians should maintain a high level of vigilance and consider routine monitoring for ITP in patients treated with this agent. This trial was registered at www.clinicaltrials.gov as #NCT00050778. (Blood. 2011;118(24):6299-6305)