| アブストラクト | 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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| ジャーナル名 | BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy |
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| 投稿日 | 2024/6/14 |
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| 投稿者 | Woods, Richard H |
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| 組織名 | Levin, Papantonio, Rafferty, Proctor, Buchanan, O'Brien, Barr and Mougey, P.A.,;316 South Baylen Street, Pensacola, FL, 32502, USA. rwoods@levinlaw.com. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38874875/ |
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