Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.1836 Dr. Jessie Torgersen et al.
Points
- The US Department of Veterans Affairs conducted an extensive analysis of 194 medications suspected of causing acute liver injury (ALI) using real-world data from 7,899,888 individuals without preexisting liver or biliary disease, covering the period from October 2000 to September 2021.
- The study identified a wide range of incidence rates of hospitalization for severe ALI across the medications studied, from 0 events per 10,000 person-years for drugs like candesartan and minocycline to 86.4 events per 10,000 person-years for stavudine.
- Medications such as erlotinib, lenalidomide, thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid had rates exceeding 10.0 events per 10,000 person-years. Others, including moxifloxacin and azathioprine, showed rates between 5.0 and 9.9 events per 10,000 person-years.
- The study revealed significant discrepancies between the hepatotoxicity categorizations based on traditional case reports and real-world data. Notably, based on case reports, 64% of the 17 medications with the highest ALI rates were not classified in the highest hepatotoxicity category.
- The findings highlight the need for incorporating population-based epidemiologic data into safety assessments to improve the identification of high-risk medications. This approach can enhance public health policies and clinical decision-making, ensuring a more accurate understanding of medication safety.
Summary
In a comprehensive analysis conducted by the US Department of Veterans Affairs, researchers evaluated the hepatotoxic potential of 194 medications suspected of causing acute liver injury (ALI) using real-world data from 7,899,888 individuals without preexisting liver or biliary disease. This population initiated these medications in an outpatient setting between October 2000 and September 2021. The study focused on identifying medications with the highest real-world incidence rates of severe ALI and compared these findings with hepatotoxic categorizations derived from published case reports, which traditionally do not account for the exposure size.
The findings revealed a wide range of incidence rates of hospitalization for severe ALI, defined by specific biochemical criteria, across the medications studied. The rates varied from 0 events per 10,000 person-years for drugs like candesartan and minocycline to a high of 86.4 events per 10,000 person-years for stavudine. Notably, medications such as erlotinib, lenalidomide, thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid exhibited rates exceeding 10.0 events per 10,000 person-years. An additional group of medications, including moxifloxacin, azathioprine, and several others, showed rates between 5.0 and 9.9 events per 10,000 person-years. Interestingly, based on case reports, 64% of these 17 medications with the highest rates were not classified in the highest hepatotoxicity category.
This study underscores the significant discrepancies between hepatotoxicity categorizations based on traditional case reports and those derived from real-world data, highlighting the need for incorporating population-based epidemiologic data into safety assessments. The results suggest that many medications commonly perceived as safe based on limited case reports may pose a higher risk of severe ALI, emphasizing the importance of real-world data in refining our understanding of medication safety. This approach can improve the identification of high-risk medications and guide more accurate public health policies and clinical decision-making.
Link to the article: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2820267
References Torgersen, J., Mezochow, A. K., Newcomb, C. W., Carbonari, D. M., Hennessy, S., Rentsch, C. T., Park, L. S., Tate, J. P., Bräu, N., Bhattacharya, D., Lim, J. K., Mezzacappa, C., Njei, B., Roy, J. A., Taddei, T. H., Justice, A. C., & Lo Re, V., III. (2024). Severe Acute Liver Injury After Hepatotoxic Medication Initiation in Real-World Data. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.1836
