预防性皮下C1抑制剂长期治疗遗传性血管性水肿患者的按需用药模式

IF 2.4
D. Levy, J. Chiao, J. Dang, C. Hood, D. Supina, H. Feuersenger
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引用次数: 0

摘要

摘要背景:遗传性血管性水肿(HAE)的特点是血管性水肿的复发性、衰弱性发作,可能需要立即(按需)治疗。HAE预防性治疗可以通过降低发作的频率和严重程度来减少对按需治疗的需求,这反过来可能会影响治疗成本。经美国食品药品监督管理局批准剂量为60的皮下C1抑制剂(C1-INH[SC]、HAEGARDA®、CSL Behring) IU/kg被认为是预防HAE患者发作的常规预防措施。在关键的III期COMPACT试验中,与安慰剂相比,每周两次C1-INH(SC)60的发病率中位数降低了95% IU/kg,按需用药的中位减少率>99%。目的:我们研究了接受C1-INH(SC)60治疗的患者的按需用药模式 COMPACT试验的长期开放标签扩展(OLE)中的IU/kg。方法:COMPACT试验的OLE是一项多中心、国际、随机、平行臂研究,评估年龄≥6岁的患者 在入组前连续2个月内有≥4次发作的年。该试验包括COMPACT试验的患者和C1-INH(SC)-幼稚患者。患者随机接受C1-INH(SC)40 IU/kg或60 IU/kg,每周两次,每次52 周或最多140 周(仅限美国患者)。HAE发作药物使用的时间标准化次数是一个探索性终点。结果:在60名患者中的63名患者中 IU/kg组,35例共371次发作,其中229例(61.7%)接受按需药物治疗:84%(192/229)接受1种药物治疗,62%接受C1-INH(IV)治疗,38%接受艾替班治疗。大多数接受治疗的发作(113/229)是严重的。共有28名患者(44.4%)没有发作,11名患者(17.5%)没有治疗发作,24名患者(38.1%)有≥1次治疗发作。对年度按需用药的事后分析显示,接受C1-INH(SC)60治疗的39名患者(61.9%) IU/kg未使用任何按需用药;66.7%的人每年使用少于一次(平均(SD):3.8(9.6)次/年;中位数:0.0次/年)。在第25个月至第30个月期间,87%的患者(20/23)没有使用任何按需用药(平均值:0.08/月,或~1次使用/年)。结论:在OLE研究中,C1-INH(SC)预防性治疗期间,随需应变的药物使用率一直很低,三分之二的患者每年用药少于一次。在HAE预防性治疗的成本效益分析中,应考虑随时间减少按需用药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Patterns of on-demand medication use in patients with hereditary angioedema treated long-term with prophylactic subcutaneous C1-inhibitor
Abstract Background: Hereditary angioedema (HAE) is characterized by recurrent, debilitating attacks of angioedema that may require immediate (on-demand) treatment. HAE prophylactic therapy may reduce the need for on-demand treatment by decreasing the frequency and severity of attacks, which may in turn impact treatment costs. Subcutaneous C1-inhibitor (C1-INH [SC], HAEGARDA®, CSL Behring) at the FDA-approved dose of 60 IU/kg is indicated as routine prophylaxis to prevent attacks in patients with HAE. In the pivotal phase III COMPACT trial, the median reduction in attack rate relative to placebo was 95% with twice-weekly C1-INH (SC) 60 IU/kg, and the median reduction in on-demand medication use was >99%. Aims: We examined patterns of on-demand medication use in patients treated with C1-INH (SC) 60 IU/kg in a long-term, open-label extension (OLE) of the COMPACT trial. Methods: The OLE of the COMPACT trial was a multicenter, international, randomized, parallel-arm study that evaluated patients aged ≥6 years with ≥4 attacks over 2 consecutive months before enrollment. The trial included patients from the COMPACT trial and C1-INH (SC)-naïve patients. Patients were randomized to receive C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 weeks or up to 140 weeks (US patients only). The time-normalized number of uses of medication for treatment of HAE attacks was an exploratory endpoint. Results: Of the 63 patients in the 60 IU/kg group, 35 had a total of 371 attacks, of which 229 (61.7%) were treated with on-demand medication: 84% (192/229) were treated with 1 medication, 62% with C1-INH (IV), and 38% with icatibant. The majority of treated attacks (113/229) were severe. A total of 28 patients (44.4%) had no attacks, 11 (17.5%) had no treated attacks, and 24 (38.1%) had ≥1 treated attack. Post-hoc analysis of annualized on-demand medication use showed that 39 patients (61.9%) treated with C1-INH (SC) 60 IU/kg did not use any on-demand medication; 66.7% used it less than once per year (mean (SD): 3.8 (9.6) uses/year; median: 0.0 uses/year). Between months 25 and 30, 87% of patients (20/23) did not use any on-demand medication (mean: 0.08/month, or ∼1 use/year). Conclusions: On-demand medication use remained consistently low during prophylactic therapy with C1-INH (SC) in the OLE study, with two-thirds of patients using medication less than once per year. Reduction in on-demand medication use over time should be considered in cost-effectiveness analyses of HAE prophylactic therapies.
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来源期刊
Journal of Drug Assessment
Journal of Drug Assessment PHARMACOLOGY & PHARMACY-
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