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JAK抑制剂的骨折相关安全性报告:来自世界卫生组织全球药物警戒数据库的分析

Fracture-Related Safety Reporting of JAK Inhibitors: An Analysis from the WHO Global VigiBase.

作者信息

Martinez de la Torre Adrian, Clausen Andreas Bech, Burden Andrea M, Weiler Stefan

机构信息

Pharmacoepidemiology Group, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich ETH Zürich, HCI H 407 Vladimir-Prelog-Weg 1-5/10, 8093, Zurich, Switzerland.

Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Drug Saf. 2025 Feb;48(2):191-201. doi: 10.1007/s40264-024-01490-w. Epub 2024 Nov 27.


DOI:10.1007/s40264-024-01490-w
PMID:39604587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11785614/
Abstract

INTRODUCTION: The Janus kinase (JAK) inhibitors are treatment options for autoimmune diseases. Numerous safety concerns have been raised. The European Medicines Agency updated the product information of tofacitinib to include the risk of fractures-but not for other JAK inhibitors. We conducted a global pharmacovigilance analysis of previously investigated JAK inhibitors to investigate a potential class effect. METHODS: Individual case safety reports (ICSRs) for all licensed JAK inhibitors were identified from the global WHO pharmacovigilance database. The primary outcome of interest was a bone fracture. Disproportionality analyses using reporting odds ratios (RORs) were conducted. RESULTS: We identified 122,037 ICSRs for tofacitinib, 27,786 ICSRs for upadacitinib, 14,616 ICSRs for baricitinib, 830 for filgotinib, and 350 for abrocitinib. Among the ICSRs, we identified 2198 (1.8%), 634 (2.3%), and 144 (1.0%) reports, where a bone fracture was reported for tofacitinib, upadacitinib, and baricitinib, respectively. Few reports were available for the newest drugs filgotinib (10) and abrocitinib (1). JAK inhibitors were associated with increased reporting for fracture: tofacitinib (ROR 3.34, 95% confidence interval [CI] 3.20-3.48), upadacitinib (ROR 4.23, 95% CI 3.80-4.48), baricitinib (ROR 1.80, 95% CI 1.52-2.11) and filgotinib (ROR 2.24, 95% CI 1.11-3.94). Patients with bone fractures were more often female, older and had a higher number of co-reported medications. They were more likely to use glucocorticoids, opioids, and bisphosphonates. CONCLUSION: The results from this pharmacovigilance analysis, based on a spontaneous reporting database associated with inherent limitations, suggest a potential risk of fractures with JAK inhibitors, indicating that a class effect cannot be ruled out.

摘要

引言:Janus激酶(JAK)抑制剂是自身免疫性疾病的治疗选择。人们提出了许多安全问题。欧洲药品管理局更新了托法替布的产品信息,纳入了骨折风险,但其他JAK抑制剂未作此更新。我们对之前研究过的JAK抑制剂进行了全球药物警戒分析,以调查潜在的类效应。 方法:从世界卫生组织全球药物警戒数据库中识别所有已获许可的JAK抑制剂的个体病例安全报告(ICSR)。主要关注的结果是骨折。使用报告比值比(ROR)进行不成比例分析。 结果:我们识别出托法替布的ICSR有122,037份,乌帕替尼的有27,786份,巴瑞替尼的有14,616份,非戈替尼的有830份,阿布罗替尼的有350份。在这些ICSR中,我们分别识别出2198份(1.8%)、634份(2.3%)和144份(1.0%)报告,其中托法替布、乌帕替尼和巴瑞替尼报告了骨折情况。关于最新药物非戈替尼(10份)和阿布罗替尼(1份)的报告很少。JAK抑制剂与骨折报告增加相关:托法替布(ROR 3.34,95%置信区间[CI] 3.20 - 3.48)、乌帕替尼(ROR 4.23,95% CI 3.80 - 4.48)、巴瑞替尼(ROR 1.80,95% CI 1.52 - 2.11)和非戈替尼(ROR 2.24,95% CI 1.11 - 3.94)。骨折患者女性更多、年龄更大且同时报告的药物数量更多。他们更有可能使用糖皮质激素、阿片类药物和双膦酸盐。 结论:基于一个存在固有局限性的自发报告数据库的药物警戒分析结果表明,JAK抑制剂存在潜在的骨折风险,这表明不能排除类效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a82/11785614/5290cc2e8481/40264_2024_1490_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a82/11785614/74d206a3319c/40264_2024_1490_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a82/11785614/5290cc2e8481/40264_2024_1490_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a82/11785614/74d206a3319c/40264_2024_1490_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a82/11785614/5290cc2e8481/40264_2024_1490_Fig2_HTML.jpg

相似文献

[1]
Fracture-Related Safety Reporting of JAK Inhibitors: An Analysis from the WHO Global VigiBase.

Drug Saf. 2025-2

[2]
Thromboembolic Safety Reporting of Tofacitinib and Baricitinib: An Analysis of the WHO VigiBase.

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[3]
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Clin Rheumatol. 2025-4

[4]
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[5]
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Pediatr Dermatol. 2024

[6]
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Sci Rep. 2022-5-3

[7]
Efficacy and Safety of Tofacitinib, Baricitinib, and Upadacitinib for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Mayo Clin Proc. 2020-6-1

[8]
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Aliment Pharmacol Ther. 2025-2

[9]
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J Eur Acad Dermatol Venereol. 2022-11

[10]
The efficacy and safety of different Janus kinase inhibitors as monotherapy in rheumatoid arthritis: A Bayesian network meta-analysis.

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本文引用的文献

[1]
The REporting of A Disproportionality Analysis for DrUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance (READUS-PV): Explanation and Elaboration.

Drug Saf. 2024-6

[2]
JAK inhibition ameliorates bone destruction by simultaneously targeting mature osteoclasts and their precursors.

Inflamm Regen. 2023-3-3

[3]
Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics.

Front Pharmacol. 2023-1-18

[4]
Fracture in clinical studies of tofacitinib in rheumatoid arthritis.

Ther Adv Musculoskelet Dis. 2022-12-27

[5]
Quercetin Loaded Cationic Solid Lipid Nanoparticles in a Mucoadhesive In Situ Gel-A Novel Intravesical Therapy Tackling Bladder Cancer.

Pharmaceutics. 2022-11-20

[6]
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update.

Ann Rheum Dis. 2023-1

[7]
A Comprehensive Overview of Globally Approved JAK Inhibitors.

Pharmaceutics. 2022-5-6

[8]
Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database.

Sci Rep. 2022-5-3

[9]
Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews.

Front Pharmacol. 2022-1-11

[10]
Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis.

N Engl J Med. 2022-1-27

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