Postmarketing Reports of Incomplete Dosing-Related Complications with Self-Injected PCSK9 Inhibitors: A Descriptive Study and Disproportionality Analysis.

IF 5.4 2区医学 Q1 IMMUNOLOGY

BioDrugs Pub Date : 2024-07-01 Epub Date: 2024-06-14 DOI:10.1007/s40259-024-00664-3

Richard H Woods

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引用次数: 0

Abstract

Background: Evolocumab and alirocumab are self-injected proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors indicated for low-density lipoprotein cholesterol reduction. Complications in the use or functionality of self-injection devices may precipitate incomplete dosing.

Objective: This study sought to characterize postmarketing dosing failure reports involving self-injected PCSK9 inhibitors.

Methods: US Food and Drug Administration Adverse Event Reporting System (FAERS) [2016-second quarter of 2023] data were utilized for a disproportionality analysis. Eight self-injected comparator medications served as referents. Medical Dictionary for Regulatory Activities preferred terms indicating explicit or probable failure to administer a complete dose classified cases. Proportional reporting ratios (PRRs) > 2.0 and lower 95% confidence intervals (CIs) > 1.0 indicated disproportionality signals. US FDA Manufacturer and User Facility Device Experience (MAUDE) [2013-2023] data underwent a narrative review.

Results: During the study period, 194,781 (evolocumab, n = 152,831; alirocumab, n = 41,950) drug-event pairs and 43,725 (evolocumab, n = 38,489; alirocumab, n = 5236) cases reported to FAERS identified PCSK9 inhibitors. MAUDE contained six evolocumab reports, half describing dose omission, and no alirocumab reports. A potential dosing failure signal was detected for evolocumab (PRR 2.01; 95% CI 1.98-2.03), but not alirocumab (PRR 0.99; 95% CI 0.97-1.02), relative to pooled comparator reports. Across three case term subcategories, incomplete dosing disproportionality signals were further identified for evolocumab patient usage complication terms (PRR 3.44; 95% CI 3.38-3.50) and alirocumab device malfunction terms (PRR 2.09; 95% CI 1.98-2.22).

Conclusions: Proprotein convertase subtilisin kexin type 9 inhibitor incomplete dosing-related complications are frequently reported in the postmarketing setting. Systematic efforts to understand the incidence and mechanisms of dosing failure and associated patient burdens are needed.

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自行注射 PCSK9 抑制剂的不完全给药相关并发症的上市后报告：描述性研究和比例失调分析。

背景：Evolocumab和alirocumab是自体注射丙蛋白转换酶亚基克星9型（PCSK9）抑制剂，用于降低低密度脂蛋白胆固醇。自行注射装置在使用或功能方面的并发症可能导致剂量不完全：本研究旨在描述涉及自行注射 PCSK9 抑制剂的上市后给药失败报告的特征：方法：利用美国食品和药物管理局不良事件报告系统（FAERS）[2016-2023 年第二季度]数据进行比例失调分析。八种自行注射的对比药物作为参照物。监管活动医学字典》（Medical Dictionary for Regulatory Activities）中表示明确或可能未给药完整剂量的首选术语对病例进行了分类。比例报告比 (PRR) > 2.0 和 95% 置信区间 (CI) > 1.0 表示比例失调信号。对美国 FDA 制造商和用户设施设备经验 (MAUDE) [2013-2023] 数据进行了叙述性审查：在研究期间，向 FAERS 报告的 194781 个（evolocumab，n = 152831；alirocumab，n = 41950）药物-事件对和 43725 个（evolocumab，n = 38489；alirocumab，n = 5236）病例确定了 PCSK9 抑制剂。MAUDE 包含六份依维莫司报告，其中一半描述了剂量遗漏，没有阿利珠单抗报告。相对于汇总的参照物报告，evolocumab（PRR 2.01；95% CI 1.98-2.03）发现了潜在的给药失败信号，而阿利珠单抗（PRR 0.99；95% CI 0.97-1.02）未发现该信号。在三个病例术语子类别中，evolocumab患者使用并发症术语（PRR为3.44；95% CI为3.38-3.50）和阿利珠单抗设备故障术语（PRR为2.09；95% CI为1.98-2.22）进一步确定了不完全的剂量比例失调信号：在上市后环境中，经常有报告称 Proprotein convertase subtilisin kexin type 9 inhibitor 不完全用药相关并发症。需要系统地了解给药失败的发生率和机制以及相关的患者负担。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BioDrugs 医学-免疫学

CiteScore

12.60

自引率

2.90%

发文量

审稿时长

>12 weeks

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