Hepatotoxicity Score: A New Method to Adjust for Use of Potentially Hepatotoxic Medications by Chronic Liver Disease Status.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacoepidemiology and Drug Safety Pub Date : 2024-12-01 DOI:10.1002/pds.70069

Vincent Lo Re, Craig W Newcomb, Dean M Carbonari, Alyssa K Mezochow, Sean Hennessy, Christopher T Rentsch, Lesley S Park, Janet P Tate, Norbert Bräu, Debika Bhattacharya, Joseph K Lim, Catherine Mezzacappa, Basile Njei, Jason A Roy, Tamar H Taddei, Amy C Justice, Jessie Torgersen

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引用次数: 0

Abstract

Background: Studies evaluating the hepatic safety of medications have been limited by the inability to control for confounding from receipt of other hepatotoxic drugs.

Objective: The objective of this study was to develop an index (Hepatotoxicity Score) to adjust for concomitant hepatotoxic medication exposure within pharmacoepidemiology studies.

Methods: We identified 193 medications with ≥ 4 reports of hepatotoxicity and created cohorts of outpatient initiators in the Veterans Health Administration (2000-2021). Exposure occurred from initiation through 30 days after discontinuation or up to 1 year. We measured age-/sex-adjusted rates of hospitalization for severe acute liver injury (ALI) by chronic liver disease (CLD), identified drugs with high rates, and used these rates as weights in the score. To demonstrate real-world use, we calculated the score for proton pump inhibitor (PPI) initiators. We summed the weights of the drugs dispensed within 90 days prior to PPI initiation. Hazard ratios (HRs) of severe ALI (95% confidence intervals) were measured with and without adjustment for Hepatotoxicity Score.

Results: Among 89 512 PPI initiators with CLD, HRs of severe ALI were higher for lansoprazole (HR = 2.17 [95% CI, 1.24-3.82]), but not pantoprazole (HR = 0.83 [95% CI, 0.61-1.13]), versus omeprazole. Adjustment for Hepatotoxicity Score attenuated HRs of lansoprazole (HR = 1.99 [95% CI, 1.13-3.50]). Among 2 462 414 PPI initiators without CLD, HRs were not significantly higher for lansoprazole (HR = 1.66 [95% CI, 0.99-2.77]) but were significantly lower for pantoprazole (HR = 0.59 [95% CI, 0.37-0.95]), versus omeprazole. Adjustment for Hepatotoxicity Score attenuated HRs of lansoprazole (HR = 1.52 [95% CI, 0.91-2.54]).

Conclusions: The Hepatotoxicity Score provides a tool to adjust for confounding due to concomitant hepatotoxic drug exposure within hepatic safety studies.

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肝毒性评分：一种根据慢性肝病状况调整潜在肝毒性药物使用的新方法。

背景：由于无法控制其他肝毒性药物引起的混淆，评估药物的肝脏安全性的研究受到限制。目的：本研究的目的是建立一个指数（肝毒性评分），以调整药物流行病学研究中伴随的肝毒性药物暴露。方法：我们在退伍军人健康管理局（2000-2021）中确定了193种有4例以上肝毒性报告的药物，并建立了门诊启动者队列。暴露发生于开始用药至停药后30天或长达1年。我们测量了慢性肝病（CLD）引起的严重急性肝损伤（ALI）的年龄/性别调整住院率，确定了高住院率的药物，并将这些住院率作为评分的权重。为了演示实际应用，我们计算了质子泵抑制剂（PPI）引发剂的分数。我们对开始使用PPI前90天内分配的药物的重量进行了汇总。在有无肝毒性评分调整的情况下测量严重ALI的危险比（95%置信区间）。结果：在89,512例伴有CLD的PPI启动者中，兰索拉唑的严重ALI的HR高于奥美拉唑（HR = 2.17 [95% CI, 1.24-3.82]），而泮托拉唑的HR低于奥美拉唑（HR = 0.83 [95% CI, 0.61-1.13]）。调整肝毒性评分降低兰索拉唑的HR （HR = 1.99 [95% CI, 1.13-3.50]）。在2462 414例未发生CLD的PPI启动者中，与奥美拉唑相比，兰索拉唑的HR没有显著升高（HR = 1.66 [95% CI, 0.99-2.77]），而泮托拉唑的HR显著降低（HR = 0.59 [95% CI, 0.37-0.95]）。调整肝毒性评分降低兰索拉唑的HR （HR = 1.52 [95% CI, 0.91-2.54]）。结论：肝毒性评分提供了一种在肝安全研究中校正伴随肝毒性药物暴露引起的混淆的工具。

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.