Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival
Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival
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DOI：
10.1182/blood-2011-02-333997
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发表时间：
2011-06-23
期刊：
影响因子：
20.3
通讯作者：
Hillmen, Peter
中科院分区：
文献类型：
--
作者：
Kelly, Richard J.;Hill, Anita;Hillmen, Peter
阵发性睡眠性血红蛋白尿症（PNH）是一种获得性克隆性造血系统疾病，由于血管内溶血导致发病率和死亡率增加。依库珠单抗是一种针对补体蛋白5的单克隆抗体，可阻止PNH中的血管内溶血。我们评估了2002年5月至2010年7月期间在利兹接受依库珠单抗治疗的79名连续患者。接受依库珠单抗治疗的患者的生存率与年龄和性别匹配的正常对照组没有差异（P = 0.46），但明显优于接受依库珠单抗治疗的30名类似患者（P = 0.030）。3名接受依库珠单抗治疗的患者，年龄均超过50岁，死于与PNH无关的原因。21例患者（27%）在开始使用依库珠单抗前发生血栓形成（5.6例事件/100患者-年），而依库珠单抗组有2例血栓形成（0.8例事件/100患者-年; P <0.001）。21例既往无血栓形成的患者停用华法林治疗依库珠单抗，无血栓后遗症。61例接受依库珠单抗治疗超过12个月的患者中有40例（66%）实现了输血独立性。12个月的平均输血需求从艾库组单抗治疗前的19.3单位减少到最近12个月的5.0单位（P < .001）。依库珠单抗显著改变了PNH的自然病程，减少了症状和疾病并发症，并将生存率提高到与普通人群相似的水平。（血。2011;117（25）：6786-6792）
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder with increased mortality and morbidity resulting from intravascular hemolysis. Eculizumab, a monoclonal antibody against the complement protein 5, stops the intravascular hemolysis in PNH. We evaluated 79 consecutive patients treated with eculizumab in Leeds between May 2002 and July 2010. The survival of patients treated with eculizumab was not different from age-and sex-matched normal controls (P = .46) but was significantly better than 30 similar patients managed before eculizumab (P = .030). Three patients on eculizumab, all over 50 years old, died of causes unrelated to PNH. Twenty-one patients (27%) had a thrombosis before starting eculizumab (5.6 events per 100 patient-years) compared with 2 thromboses on eculizumab (0.8 events per 100 patient-years; P < .001). Twenty-one patients with no previous thrombosis discontinued warfarin on eculizumab with no thrombotic sequelae. Forty of 61 (66%) patients on eculizumab for more than 12 months achieved transfusion independence. The 12-month mean transfusion requirement reduced from 19.3 units before eculizumab to 5.0 units in the most recent 12 months on eculizumab (P < .001). Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to a similar level to that of the general population. (Blood. 2011;117(25):6786-6792)