Potential Drug Dose-Specific Adverse Three-Drug Combinations: A US Insurance Claims Data-Based Study.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacoepidemiology and Drug Safety Pub Date : 2025-09-01 DOI:10.1002/pds.70199

Y Shi, A Sun, C W Chiang, Y Yang, K M Hunold, J Xu, M Russo, J Caterino, M T Eadon, L Li, J Su, M Donneyong, P Zhang

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引用次数: 0

Abstract

Introduction: Use of three-drug combinations is increasingly prevalent and associated with an increased risk of adverse drug events (ADEs). While real-world data-based pharmacovigilance and pharmacoepidemiology studies have derived knowledge on potential adverse three-drug combinations, the relationship between doses of each drug in three-drug combination exposure and the risk of ADEs remains unclear.

Methods: We derived matched case-control datasets from US nationwide health insurance claims data for potential ADEs including acute kidney injury, acute myocardial infarction, gastrointestinal bleeding, hypoglycemia, and opioid-related ADE. We used the conditional logistic regression model to investigate the relationship between the dose of three-drug combination exposure and the risk of ADE. We used Benjamini and Hochberg's procedure to control the false discovery rate (FDR). We explored the relationship between the reduction of drug dose and the risk of ADE.

Results: We identified over 500 potential adverse three-drug combinations from approximately two million case-control pairs (all odds ratios ≥ 1.3 and FDR < 0.05). For the signals, compared with a high-dose level of all three drugs, 74% of three-drug combinations had a lower risk by decreasing the dose of one drug without any drug discontinuation (p value < 0.05).

Conclusions: Certain three-drug combinations are associated with an increased risk of ADE. Dose of exposure might be used to evaluate the risk of ADE for a majority of adverse three-drug combinations.

Plain language summary: Use of three-drug combinations is increasingly prevalent and associated with an increased risk of adverse drug events (ADEs). We identified potential adverse three-drug combinations from real-world data, and revealed the corresponding relationships between doses and risks of ADEs. We find doses might be used to evaluate the risk of ADE for many adverse three-drug combinations. Additionally, we find risk of many adverse three-drug combinations might be decreased by reducing the dose of one drug without any drug discontinuation.

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潜在的药物剂量特异性不良三种药物组合：一项基于美国保险索赔数据的研究。

三药联合使用越来越普遍，并与药物不良事件（ADEs）的风险增加相关。虽然基于真实世界数据的药物警戒和药物流行病学研究已经获得了潜在不良三药联合暴露的知识，但三药联合暴露中每种药物的剂量与ade风险之间的关系仍不清楚。方法：我们从美国全国健康保险索赔数据中获得匹配的病例对照数据集，包括急性肾损伤、急性心肌梗死、胃肠道出血、低血糖和阿片类药物相关的ADE。我们采用条件logistic回归模型探讨三药联合暴露剂量与ADE风险的关系。我们使用Benjamini和Hochberg的程序来控制错误发现率（FDR）。我们探讨了药物剂量的减少与ADE风险之间的关系。结果：我们从大约200万对病例对照中确定了500多种潜在的不良三联用药（所有比值比≥1.3和FDR）。结论：某些三联用药与ADE风险增加相关。暴露剂量可用于评估大多数不良三联用药的ADE风险。简明扼要：三种药物联合使用越来越普遍，并与药物不良事件（ADEs）的风险增加有关。我们从真实世界的数据中确定了潜在的不良三药组合，并揭示了剂量与ade风险之间的对应关系。我们发现剂量可以用来评估许多不良的三药联合ADE的风险。此外，我们发现许多不良的三种药物联合的风险可能会通过减少一种药物的剂量而不停药而降低。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacoepidemiology and Drug Safety 医学-药学

CiteScore

4.80

自引率

7.70%

发文量

173

审稿时长

3 months

期刊介绍： The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report. Particular areas of interest include: design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology; comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world; methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology; assessments of harm versus benefit in drug therapy; patterns of drug utilization; relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines; evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.