West Joseph B, Poarch Kimberly, Lumry William R
Allergy & Asthma Specialists, Dallas, Texas.
Allergy & Asthma Specialists, Dallas, Texas.
Clin Ther. 2021 Dec;43(12):2154-2166.e1. doi: 10.1016/j.clinthera.2021.10.008. Epub 2021 Dec 5.
Hereditary angioedema (HAE), most often caused by a genetically mediated deficiency in the activity of C1 inhibitor (C1INH) protein, is characterized clinically by recurrent episodes of localized swelling without wheals. HAE attacks can be painful, debilitating, and even fatal, resulting in physical discomfort, emotional stress, and interruptions of work, school, and/or social activities, all of which can affect health-related quality of life (HRQoL). Subcutaneous C1INH (C1INH[SC]) is recommended as a first-line option for long-term prophylaxis (LTP) in HAE. This narrative review provides a concise but comprehensive overview of all published data generated from the pivotal Phase III Clinical Study for Optimal Management of Preventing Angioedema With Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT) study program, which evaluated the use of C1INH(SC) as LTP.
A PubMed search was performed using the search terms subcutaneous C1 inhibitor plus COMPACT with no filters, and another search was performed using the term subcutaneous C1 inhibitor, with output limited to clinical trial data only. All publications that reported data generated during the Phase III COMPACT study were included. Data presentation focused on the US Food and Drug Administration-approved dose of 60 IU/kg.
The search strategy identified a total of 11 publications that reported data and analyses from the Phase III COMPACT study. Publications reported overall findings from the double-blind, placebo-controlled, crossover COMPACT study and a subsequent long-term open-label extension (OLE) study. Other published analyses included pharmacokinetic/pharmacodynamic data, HRQoL assessments, and findings in patient subgroups including women, pediatric patients, and patients ≥65 years of age. Subgroup analyses reported good safety and efficacy profiles among age-based subgroups from the COMPACT OLE, including pediatric patients, patients ≥65 years of age with comorbidities, and among female patients, despite a tendency for HAE to be more severe in women. A number of significant HRQoL improvements were noted with C1INH(SC) use, including better overall health status, less anxiety, and less work- and activity-related impairment versus placebo (double-blind study), and compared with baseline (OLE).
This review provides a concise overview of all published COMPACT study data with C1INH(SC). The data reviewed here portray a high level of efficacy and tolerability with C1INH(SC), even during periods of treatment that exceed 2 years, which does not appear to vary based on patient age or sex. Clinically relevant improvements in multiple facets of HRQoL were also reported, including better overall HRQoL, less anxiety and depression, and less disruptions in work attendance and productivity. These data should be useful for assessing the appropriateness of C1INH(SC) therapy for individual patients.
遗传性血管性水肿（HAE）通常由基因介导的C1抑制剂（C1INH）蛋白活性缺乏引起，临床特征为反复出现局限性肿胀且无风团。HAE发作可能会疼痛、使人虚弱甚至致命，导致身体不适、情绪压力以及工作、学习和/或社交活动中断，所有这些都会影响健康相关生活质量（HRQoL）。皮下注射C1INH（C1INH[SC]）被推荐作为HAE长期预防（LTP）的一线选择。本叙述性综述简要而全面地概述了从预防血管性水肿的低容量皮下C1抑制剂替代疗法最佳管理关键III期临床研究（COMPACT）研究项目中产生的所有已发表数据，该项目评估了C1INH（SC）作为LTP的使用情况。
在PubMed上进行搜索，搜索词为皮下C1抑制剂加COMPACT且不设筛选条件，另一次搜索使用皮下C1抑制剂一词，输出仅限于临床试验数据。纳入所有报告在III期COMPACT研究期间产生的数据的出版物。数据呈现聚焦于美国食品药品监督管理局批准的60 IU/kg剂量。
搜索策略共识别出11篇报告III期COMPACT研究数据和分析的出版物。这些出版物报告了双盲、安慰剂对照、交叉COMPACT研究以及随后的长期开放标签扩展（OLE）研究的总体结果。其他已发表的分析包括药代动力学/药效学数据、HRQoL评估以及患者亚组的结果，包括女性、儿科患者和≥65岁的患者。亚组分析报告了COMPACT OLE基于年龄的亚组中良好的安全性和有效性概况，包括儿科患者、≥65岁有合并症的患者以及女性患者，尽管HAE在女性中往往更严重。与安慰剂（双盲研究）相比以及与基线（OLE）相比，使用C1INH（SC）后在多个HRQoL方面有显著改善，包括更好的总体健康状况、更少的焦虑以及更少的工作和活动相关损害。
本综述简要概述了所有已发表的关于C1INH（SC）的COMPACT研究数据。此处回顾的数据表明C1INH（SC）具有高度的有效性和耐受性，即使在超过2年的治疗期间也是如此，且似乎不因患者年龄或性别而有所不同。还报告了HRQoL多个方面的临床相关改善，包括更好的总体HRQoL、更少的焦虑和抑郁以及更少的工作出勤和生产力中断。这些数据对于评估C1INH（SC）治疗对个体患者的适用性应是有用的。
