DasGupta Ryan K, Levine Lauren, Wiczer Tracy, Cataland Spero
1 Department of Pharmacy, The Ohio State University James Cancer Hospital, Columbus, OH, USA.
2 Department of Pharmaceutical Services, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
J Oncol Pharm Pract. 2019 Apr;25(3):567-576. doi: 10.1177/1078155217748470. Epub 2018 Jan 3.
BACKGROUND/RATIONALE: Romiplostim is a thrombopoietin receptor agonist recommended as a second-line therapy for immune thrombocytopenia. An initial dose of 1 mcg/kg/week subcutaneously with weekly 1 mcg/kg dose escalation is recommended per package labeling. Optimizing romiplostim dosing for hospitalized, corticosteroid- and intravenous immunoglobulin-refractory patients with severe thrombocytopenia secondary to immune thrombocytopenia may be critical for improving platelet responses, reducing the risk of bleeding, and decreasing hospital length of stay. Limited data are available evaluating the efficacy and safety of higher initial doses.
The primary objective of this study was to compare the time to platelet ≥ 10 × 10/L between patients who received an initial romiplostim dose of ≥2 mcg/kg/week compared to the standard initial dose of 1 mcg/kg/week. Secondary objectives included time to platelet response ≥ 30 × 10/L and ≥50 × 10/L, percentage of patients achieving platelet responses, hospital length of stay, and incidence of adverse events and bleeding complications.
This was a retrospective, single-center, cohort study including hospitalized adults with corticosteroid- and intravenous immunoglobulin-refractory immune thrombocytopenia. A baseline platelet < 10 × 10/L was required. Patients were stratified by their initial romiplostim dose into Cohort 1 (1 mcg/kg/week) and Cohort 2 (≥2 mcg/kg/week). A review of electronic medical records and descriptive statistics generated findings.
A total of 18 patients were included, 4 in Cohort 1 and 14 in Cohort 2. Patients in Cohort 2 had a median initial dose of 4.5 mcg/kg/week. Patients in Cohort 2 achieved a platelet ≥ 10 × 10/L in a median of 2 days versus 4.5 days for Cohort 1. More patients in Cohort 2 achieved a platelet ≥ 30 × 10/L (42.9% vs. 25%) and platelet ≥ 50 × 10/L (28.6% vs. 25%). The median hospital length of stay was shorter in Cohort 2 (13.5 vs. 20 days). Clinically relevant nonmajor bleeding was noted less frequently in Cohort 2 (28.6% vs. 75%), while major bleeding was more frequent in Cohort 2 (14.3% vs. 0%). No thrombotic events occurred.
Our study suggests that higher initial romiplostim doses may be safe for hospitalized patients with treatment-refractory immune thrombocytopenia. Compared to Food and Drug Administration-approved dosing, higher initial doses may shorten time to platelet responses and hospital length of stay. Further large-scale studies are needed to confirm these findings.
背景/理论依据：罗米司亭是一种血小板生成素受体激动剂，被推荐作为免疫性血小板减少症的二线治疗药物。根据药品包装说明书，推荐的初始剂量为每周皮下注射1μg/kg，并每周递增1μg/kg。对于因免疫性血小板减少症导致严重血小板减少、住院且对皮质类固醇和静脉注射免疫球蛋白治疗无效的患者，优化罗米司亭剂量对于改善血小板反应、降低出血风险和缩短住院时间可能至关重要。评估更高初始剂量的疗效和安全性的数据有限。
本研究的主要目的是比较接受初始罗米司亭剂量≥2μg/kg/周的患者与标准初始剂量1μg/kg/周的患者达到血小板≥10×10⁹/L的时间。次要目标包括达到血小板反应≥30×10⁹/L和≥50×10⁹/L的时间、实现血小板反应的患者百分比、住院时间以及不良事件和出血并发症的发生率。
这是一项回顾性、单中心队列研究，纳入因皮质类固醇和静脉注射免疫球蛋白治疗无效而住院的成年免疫性血小板减少症患者。要求基线血小板计数<10×10⁹/L。根据初始罗米司亭剂量将患者分为队列1（1μg/kg/周）和队列2（≥2μg/kg/周）。通过回顾电子病历和描述性统计得出研究结果。
共纳入18例患者，队列1中有4例，队列2中有14例。队列2患者的初始剂量中位数为4.5μg/kg/周。队列2患者达到血小板≥10×10⁹/L的中位数时间为2天，而队列1为4.5天。队列2中更多患者达到血小板≥30×10⁹/L（42.9%对25%）和血小板≥50×10⁹/L（28.6%对25%）。队列2的住院时间中位数较短（13.5天对20天）。队列2中临床相关的非严重出血发生率较低（28.6%对75%），而严重出血在队列2中更常见（14.3%对0%）。未发生血栓事件。
我们的研究表明，对于治疗难治性免疫性血小板减少症的住院患者，更高的罗米司亭初始剂量可能是安全的。与美国食品药品监督管理局批准的剂量相比，更高的初始剂量可能缩短血小板反应时间和住院时间。需要进一步的大规模研究来证实这些发现。
