Long-Term Treatment with Romiplostim in Patients with Chronic Immune Thrombocytopenic Purpura (ITP): 3-Year Update from An Open-Label Extension Study
Long-Term Treatment with Romiplostim in Patients with Chronic Immune Thrombocytopenic Purpura (ITP): 3-Year Update from An Open-Label Extension Study
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Romiplostim 对慢性免疫性血小板减少性紫癜 (ITP) 患者的长期治疗：开放标签扩展研究的 3 年更新
DOI：
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
D. Berger
中科院分区：
文献类型：
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作者：
D. Kuter;J. Bussel;A. Newland;J. Wolf;T. Guthrie;J. Wasser;L. Gehl;K. Nie;D. Berger
慢性ITP的特征是血小板破坏增加和血小板生成不足。Romiplostim是一种研究性Fc-肽融合蛋白（肽体），正在研究其增加慢性ITP患者血小板计数的能力。我们报告的数据来自romiplostim在成人慢性ITP患者中的开放标签扩展研究。正在收集这些患者长期治疗的安全性和疗效数据。合格患者已完成既往romiplostim研究，血小板计数≥ 50×10 9 /L。罗米司亭每周一次皮下给药，调整剂量以维持血小板计数在50-250×10 9 /L。截至2007年7月13日，142名患者接受了romiplostim治疗。自诊断以来的中位时间为6.4年（范围为0.6-46.4年）。大多数是女性（67%），以前接受过脾切除术（60%）。基线血小板计数中位数为17×10 9 /L（范围1-50×10 9 /L）。中位治疗持续时间为65周（范围1-156周）。29例（20%）患者终止研究，10例（7%）患者因不良事件（AE）[骨髓网硬蛋白和血栓形成各2例;出血、疼痛、心脏骤停、肺炎、肝和肾衰竭和意义不明的单克隆丙种球蛋白病各1例]。分析了血小板计数反应的不同指标;从这些分析中排除了接受急救药物后8周内的任何血小板计数。血小板计数较基线升高≥20× 109/L的患者比例分别为54%和73%，分别为80%和50%以上。67%的患者血小板计数> 20× 109/L的时间超过90%，94%的患者超过50%。首次给药后30%（42/138）的患者、第3次给药后51%（71/138）的患者和总体87%（124/142）的患者血小板计数>50× 109/L和基线加倍。分析血小板计数升高的持久性：78%（102/131）、54%（66/122）和35%（29/84）的患者血小板计数>50× 109/L分别持续≥10、≥25和≥52周。任何严重程度和具有临床意义（≥ 3级）的出血事件的患者发生率均随时间推移而下降（表）。95%的患者报告了AE，大多数严重程度为轻度至中度。最常见的是头痛（37%）;鼻咽炎（32%）;以及挫伤、疲劳和鼻出血（各30%）。AE频率未随研究时间增加（表）。8例患者骨髓网硬蛋白存在或增加，无进展为胶原纤维化或慢性特发性骨髓纤维化的证据。7例（5%）患者报告了血栓形成事件; 6例患者既存血栓形成风险因素。总之，romiplostim在大部分时间内增加了大多数患者的血小板计数，随着时间的推移，临床相关出血减少。罗米司亭耐受性良好，AE未随治疗持续时间延长而增加。表.按研究阶段列出的患者AE发生率总结
Chronic ITP is characterized by increased platelet destruction and suboptimal platelet production. Romiplostim is an investigational Fc-peptide fusion protein (peptibody) being studied for its ability to increase platelet counts in patients with chronic ITP. We report data from an open-label extension study of romiplostim in adult patients with chronic ITP. Collection of safety and efficacy data from long-term treatment of these patients is ongoing. Eligible patients had completed a prior romiplostim study and had platelet counts □50×10 9 /L. Romiplostim was administered subcutaneously once weekly with dose adjustments to maintain a platelet count of 50–250×10 9 /L. As of July 13 2007, 142 patients had been treated with romiplostim. Their median time since diagnosis was 6.4 years (range 0.6–46.4 years). Most were female (67%) and had previously undergone a splenectomy (60%). The median baseline platelet count was 17×10 9 /L (range 1–50×10 9 /L). The median duration of treatment was 65 weeks (range 1–156 weeks). Twenty-nine (20%) patients discontinued the study, 10 (7%) due to adverse events (AEs) [2 each of bone marrow reticulin and thrombosis; 1 each of bleeding, pain, cardiac arrest, pneumonia, hepatic and renal failure, and monoclonal gammopathy of undetermined significance]. Different measures of platelet count response were analyzed; any platelet counts within 8 weeks of receiving rescue medications were excluded from these analyses. Platelet counts were increased from baseline by ≥20×10 9 /L more than 80% of the time in 54% of patients and more than 50% of the time in 73% of patients. Platelet counts remained above 20×10 9 /L more than 90% of the time in 67% of patients and more than 50% of the time in 94% of patients. A platelet count >50×10 9 /L and double baseline was achieved by 30% (42/138) of patients after the first dose, by 51% (71/138) of patients after the third dose, and by 87% (124/142) of patients overall. The durability of platelet count increases was analyzed: platelet counts >50×10 9 /L were sustained for ≥10, ≥25, and ≥52 consecutive weeks in 78% (102/131), 54% (66/122), and 35% (29/84) of patients, respectively. The patient incidence of bleeding events both of any severity and of clinical significance (≥Grade 3) declined over time (Table). AEs were reported in 95% of patients, with most mild to moderate in severity. The most common were headache (37%); nasopharyngitis (32%); and contusion, fatigue and epistaxis (each 30%). AE frequency did not increase with time on study (Table). Bone marrow reticulin was present or increased in 8 patients with no evidence of progression to collagen fibrosis or chronic idiopathic myelofibrosis. Thrombotic events were reported in 7 (5%) patients; 6 had pre-existing risk factors for thrombosis. In conclusion, romiplostim increased platelet counts in most patients for most of the time, and clinically relevant bleeding was reduced over time. Romiplostim was well-tolerated and AEs did not increase with longer duration of treatment. Table. Summary of patient incidence of AEs by study period