Postmarketing Reports of Incomplete Dosing-Related Complications with Self-Injected PCSK9 Inhibitors: A Descriptive Study and Disproportionality Analysis.
BioDrugs
; 38(4): 589-600, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38874875
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vigilância de Produtos Comercializados
/
Sistemas de Notificação de Reações Adversas a Medicamentos
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Anticorpos Monoclonais Humanizados
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Inibidores de PCSK9
Limite:
Female
/
Humans
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Male
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Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
BioDrugs
Ano de publicação:
2024
Tipo de documento:
Article