Pharmacovigilance and Patient Safety, AbbVie Inc., North Chicago, IL, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Drug Saf. 2024 Apr;47(4):301-319. doi: 10.1007/s40264-023-01390-5. Epub 2024 Jan 13.
The elderly demographic is the fastest-growing segment of the world's population and is projected to exceed 1.5 billion people by 2050. With multimorbidity, polypharmacy, susceptibility to drug-drug interactions, and frailty as distinct risk factors, elderly patients are especially vulnerable to developing potentially life-threatening safety events such as serious forms of drug-induced liver injury (DILI). It has been a longstanding shortcoming that elderly individuals are often a vulnerable population underrepresented in clinical trials. As such, an improved understanding of DILI in the elderly is a high-priority, unmet need. This challenge is underscored by recent documents put forward by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) that encourage data collection in the elderly and recommend improved practices that will facilitate a more inclusive approach. To establish what is already known about DILI in the elderly and pinpoint key gaps of knowledge in this arena, a working definition of "elderly" is required that accounts for both chronologic and biologic ages and varying states of frailty. In addition, it is critical to characterize the biological role of aging on liver function, as well as the different epidemiological factors such as polypharmacy and inappropriate prescribing that are common practices. While data may not show that elderly people are more susceptible to DILI, DILI due to specific drugs might be more common in this population. Improved characterization of DILI in the elderly may enhance diagnostic and prognostic capabilities and improve the way in which liver safety is monitored during clinical trials. This summary of the published literature provides a framework to understand and evaluate the risk of DILI in the elderly. Consensus statements and recommendations can help to optimize medical care and catalyze collaborations between academic clinicians, drug manufacturers, and regulatory scientists to enable the generation of high-quality research data relevant to the elderly population.
人口老龄化是全球人口增长最快的部分，预计到 2050 年将超过 15 亿。老年人多病共存、多种药物并用、易发生药物相互作用以及身体虚弱等，都是明确的高危因素，因此特别容易发生可能危及生命的安全事件，如严重的药物性肝损伤（DILI）。长期以来，老年人临床试验代表性不足，一直是一个薄弱环节。因此，深入了解老年人的 DILI 是一个亟待解决的重要问题。美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）最近发布的文件强调了这一挑战，鼓励在老年人中收集数据，并建议改进实践，以促进更具包容性的方法。为了明确老年人 DILI 的已知情况并指出该领域的关键知识空白，需要制定一个考虑到生理年龄和生物年龄以及不同虚弱状态的老年人定义。此外，还必须描述衰老对肝功能的生物学作用，以及多药并用和不适当处方等常见做法带来的不同流行病学因素。虽然数据可能并未显示老年人更容易发生 DILI，但由于特定药物导致的 DILI 在该人群中可能更为常见。更好地描述老年人的 DILI 可能会增强诊断和预后能力，并改善临床试验中监测肝安全性的方式。本文对已发表文献进行了总结，为理解和评估老年人 DILI 的风险提供了框架。共识声明和建议有助于优化医疗服务，并促进学术临床医生、药品制造商和监管科学家之间的合作，为老年人人群生成高质量的研究数据。
