From the University of California, Los Angeles, School of Medicine, Los Angeles, California.
School of Medicine, University of Leeds, Leeds, England.
Allergy Asthma Proc. 2024 Jan 22;45(1):37-43. doi: 10.2500/aap.2024.45.230073. Epub 2023 Nov 22.
Hereditary angioedema (HAE) is characterized by recurrent and unpredictable episodes of subcutaneous and/or submucosal swelling. To characterize the real-world treatment burden associated with existing on-demand therapies, we analyzed administration-site adverse drug reactions (ADR) associated with approved on-demand HAE therapies reported in the U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). We searched the FAERS database from October 1, 2009, to March 31, 2022, for reports of all FDA-approved on-demand therapies for HAE: plasma-derived C1-inhibitor (pdC1-INH), ecallantide, icatibant, and recombinant C1-inhibitor (rhC1-INH). ADRs in which the drug was listed as the "primary suspect" were recorded for each drug. ADR preferred terms were grouped into 18 ADR domains based on semantic and/or clinical similarity, and the number of reports for each drug was calculated per year from the time of approval through March 2022, and descriptive results were presented. Preferred terms associated with administration-site ADRs identified from clinical trials and denoted on approved HAE drug U.S. package inserts were examined in a complementary analysis. The highest reported rates of administration-site ADRs per year were site pain (17.9 reports per year), site erythema (7.4 per year), and site swelling (6.7 per year). RhC1-INH was the only drug for which access-site complications and/or malfunctions were reported (9.5 per year). PdC1-INH had the highest rate of incorrect route of product administration (3.7 per year). PdC1-INH showed statistically significant elevated reporting rate of injection-site reactions (reporting odds ratio [ROR] 3.59 [2.36-5.46]; empirical Bayesian geometric mean [EBGM] 1.97 [1.39]). Icatibant and rhC1-INH showed a statistical trend toward an increased reporting rate of administration-site reactions. Real-world data from FAERS were generally consistent with adverse events reported in clinical trials and suggest that patients experience substantial treatment burden associated with FDA-approved parenteral on-demand therapies for HAE attacks. It should be noted that ADR rates are not exposure adjusted and are based on spontaneous reporting.
遗传性血管性水肿 (HAE) 的特征是反复发作且不可预测的皮下和/或黏膜下肿胀。为了描述现有按需治疗相关的实际治疗负担，我们分析了美国食品和药物管理局 (FDA) 不良事件报告系统 (FAERS) 中报告的已批准按需 HAE 治疗相关的给药部位不良反应 (ADR)。我们从 2009 年 10 月 1 日至 2022 年 3 月 31 日在 FAERS 数据库中搜索了所有 FDA 批准的按需治疗 HAE 的报告：血浆衍生的 C1 抑制剂 (pdC1-INH)、艾卡替班、依卡替班和重组 C1 抑制剂 (rhC1-INH)。记录了每种药物中药物被列为“主要嫌疑”的 ADR。根据语义和/或临床相似性，ADR 首选术语被分为 18 个 ADR 域，并且从每种药物获得批准之日起至 2022 年 3 月每年计算每种药物的报告数量，并呈现描述性结果。在补充分析中，检查了从临床试验中确定的与给药部位 ADR 相关的首选术语，并在已批准的 HAE 药物美国包装插页中注明。每年报告的给药部位 ADR 率最高的是部位疼痛 (17.9 例/年)、部位红斑 (7.4 例/年) 和部位肿胀 (6.7 例/年)。rhC1-INH 是唯一报告有进入部位并发症和/或故障的药物 (9.5 例/年)。pdC1-INH 产品给药途径错误的发生率最高 (3.7 例/年)。pdC1-INH 显示注射部位反应的报告率有统计学意义升高 (报告比值比 [ROR] 3.59 [2.36-5.46]；经验贝叶斯几何平均值 [EBGM] 1.97 [1.39])。艾卡替班和 rhC1-INH 显示给药部位反应报告率有统计学趋势增加。来自 FAERS 的真实世界数据与临床试验中报告的不良事件基本一致，表明患者经历了与 HAE 发作的 FDA 批准的肠外按需治疗相关的大量治疗负担。应该注意的是，ADR 率不是暴露调整的，并且基于自发报告。
