Martinez de la Torre Adrian, Clausen Andreas Bech, Burden Andrea M, Weiler Stefan
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.
Drug Saf. 2025 Feb;48(2):191-201. doi: 10.1007/s40264-024-01490-w. Epub 2024 Nov 27.
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.
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。
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