BMC Pharmacology & Toxicology最新文献

{"title":"Adverse event profile of crizotinib in real-world from the FAERS database: a 12-year pharmacovigilance study.","authors":"Huan Zhang, Yunrui Song, Fantong Xia, Yunchang Liu, Lu Zhang, Jieying Yang, Honglei Tu, Bin Long, Jiangdong Sui, Ying Wang","doi":"10.1186/s40360-025-00859-6","DOIUrl":"10.1186/s40360-025-00859-6","url":null,"abstract":"<p><strong>Aim: </strong>Crizotinib, an anaplastic lymphoma kinase tyrosine kinase inhibitor (ALK-TKI). It gained approval from the U.S. Food and Drug Administration (FDA) specifically for treating ALK-positive non-small cell lung cancer (NSCLC). The objective of the present investigation was to evaluate adverse events (AEs) associated with crizotinib in real-world by employing data mining on the U.S. FDA Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>Data encompassing AEs linked to crizotinib from 2011 to 2023 were gathered. Disproportionality analyses, which involved the utilization of reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed for analytical purposes.</p><p><strong>Results: </strong>A total of 10,226 reports documenting crizotinib-associated AEs were extracted from the FAERS database. Out of these, 147 preferred terms (PTs) displaying significant disproportionality were identified concurrently across all four algorithms. The most frequently observed AEs included increased transaminases, bradycardia, prolonged QT, nausea, vomiting, diarrhea, constipation, visual impairment, and interstitial lung disease, which were consistent with previous reports from clinical trials. Additionally, unexpected significant AEs such as deep vein thrombosis, pneumocystis jirovecii pneumonia, gastrointestinal amyloidosis, and hepatic coma were also observed.</p><p><strong>Conclusion: </strong>Crizotinib offers therapeutic benefits but is also accompanied by various risks in the form of AEs. Our study findings align with previous clinical observations, and furthermore, we have identified unforeseen serious AEs. This discovery serves as a novel basis for the monitoring of dosages and the identification of risks associated with crizotinib.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"61"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin attenuates metabolic dysfunction-associated steatotic liver disease by inhibiting lipid accumulation, inflammation and liver fibrosis.","authors":"Xingyu Fan, Yueyue Wang, Yue Wang, Hao Duan, Yijun Du, Tianrong Pan, Xing Zhong","doi":"10.1186/s40360-025-00898-z","DOIUrl":"10.1186/s40360-025-00898-z","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a globally prevalent liver disease, closely linked to the rising incidence of obesity, diabetes, and metabolic syndrome. Dapagliflozin (DaPa), a sodium-glucose cotransporter-2 inhibitor, is primarily prescribed for diabetes management. It has shown potential efficacy in managing MASLD in clinical settings. However, the molecular mechanisms underlying the effects of DaPa on MASLD remain poorly understood. Hence, we aimed to investigate the role of and mechanisms underlying DaPa in MASLD.</p><p><strong>Methods: </strong>Male diet-induced obese (DIO) C57BL/6J mice were injected with streptozotocin (STZ), followed by a high-fat diet regimen to stimulate metabolic dysfunction. Subsequently, they received DaPa via gavage for 5 weeks. Hepatic lipid accumulation, pathological alterations, inflammatory markers, and liver fibrosis were assessed.</p><p><strong>Results: </strong>DaPa administration reduced liver fat accumulation in DIO mice. Additionally, it decreased oxidative stress and lipid peroxide levels, which was attributed to the upregulation of glutathione and the downregulation of malondialdehyde and reactive oxygen species levels. Notably, DaPa downregulated the inflammatory response and reduced liver fibrosis.</p><p><strong>Conclusions: </strong>DaPa protects against MASLD by inhibiting lipid accumulation, inflammation, oxidative stress, and liver fibrosis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"59"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-marketing safety of elacestrant in breast cancer: a pharmacovigilance investigation using the FDA adverse event reporting system.","authors":"Ziyi Fan, Yanan Xu, Shuding Guo, Bin Song","doi":"10.1186/s40360-025-00887-2","DOIUrl":"10.1186/s40360-025-00887-2","url":null,"abstract":"<p><strong>Background: </strong>Recently, the US Food and Drug Administration approved a new oral selective estrogen receptor downregulator for breast cancer, namely, elacestrant (Orserdu). This study aimed to analyze the signals of adverse events (AEs) within the introduction of elacestrant to the market using the FDA Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>Reports on the AEs of elacestrant after its marketing were obtained from the FAERS database. Disproportionality was analyzed using the reporting odds ratio to calculate the magnitude of the risk of the target drug and the AE combination, and the proportional reporting ratio to quantify the strength of the association between the drug and the AEs.</p><p><strong>Results: </strong>A total of 3132 reports on elacestrant-related AEs were obtained, with disease progression, drug ineffectiveness, product dose omission, arthralgia, asthenia, increased tumor marker levels, and bone pain (Number of reported cases (a) ≥ 3 and lower limit of 95% confidence interval >1) being the high-frequency events not mentioned on the drug label. The top three total frequencies at the system organ class level comprised general disorders and administration site conditions, gastrointestinal disorders, and musculoskeletal and connective tissue disorders.</p><p><strong>Conclusions: </strong>FAERS data analyses were conducted to evaluate the safety of post-marketing clinical use of elacestrant and to ensure that physicians identify the risk factors for the AEs of this drug.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"56"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-market safety profile of cefiderocol: a real-world pharmacovigilance exploratory analysis based on U.S. FDA adverse event reporting system (FAERS).","authors":"Hao Lin, Chen Zhu, Shuang Liu, Yingmin Bi, Jindong Hu, Mohan Ju","doi":"10.1186/s40360-025-00894-3","DOIUrl":"10.1186/s40360-025-00894-3","url":null,"abstract":"<p><strong>Background: </strong>Cefiderocol is a new drug class, which is approved to treat Gram-negative bacteria infection. Its approval for marketing has provided clinicians with additional options for treating antimicrobial resistant gram-negative infections. The aim of our study was to assess the safety profiles of cefiderocol in real-world through data mining of the United States Food and Drug Administration Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>We included adverse event (AE) reports regarding cefiderocol submitted to the FAERS from 2019 quarter 4 (2019Q4) to 2024 quarter 3 (2024Q3). Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS) techniques were performed to identify the signals of disproportionate reporting of AEs in patients receiving cefiderocol. A signal of disproportionate reporting was detected if the lower limit of the 95% confidence interval (CI) of ROR > 1, the PRR was ≥ 2(while the Chi-Square of PRR was ≥ 4), the lower limit of 95% CI of the information component (IC025) was > 0, the lower limit of 95% CI of the Empirical Bayes Geometric Mean (EBGM05) was > 2 and at least 3 AEs were reported.</p><p><strong>Results: </strong>A total of 29 significant preferred terms (PTs) were identified among the 592 cefiderocol-associated adverse events (AEs) reports collected from the FAERS database. Cefiderocol-induced adverse events involved 24 System Organ Class (SOC). 29 positive signals of disproportionate reporting are also presented, such as Pathogen resistance (n = 16, ROR 189.35, PRR 184.26, IC 7.52, EBGM 183.89), Systemic candida (n = 3, ROR 138.79, PRR 138.19, IC7.11, EBGM 137.88), Drug resistance (n = 30, ROR 131.96, PRR 125.33, IC6.97, EBGM 125.16), and Drug effect less than expected (n = 6, ROR 68.42, PRR 67.74, IC6.08, EBGM 67.69). The most frequently observed were Death, Drug resistance and Treatment failure.</p><p><strong>Conclusions: </strong>Our findings offer significant evidence regarding the safety profile of cefiderocol in real-world settings. This information may assist clinicians and pharmacists in enhancing their vigilance and improving the overall safety of cefiderocol in clinical practice.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"58"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMD1, a cardiotoxicity target for Maduramicin.","authors":"Zi-Feng Xie, Han-Meng Liu, Jia-Fan Zhao, Yuan Gao, Yuan-Long Zhao, Jia-Yue Zheng, Xiao-Wei Pei, Ning Zhang, Ge Tian","doi":"10.1186/s40360-025-00897-0","DOIUrl":"10.1186/s40360-025-00897-0","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to investigate AMD1 cardiotoxicity function for Maduramicin (Mad).</p><p><strong>Methods: </strong>SD rats were divided into control (Control) group and Mad treatment (3.5 mg/kg) group (Mad). After treatment with Mad for seven days, the levels of LDH and CK-MB in serum were detected, H&E staining and TUNEL staining were performed. In vitro, 1.0 μm Mad was used for the subsequently experiment, observing cell apoptosis from Flow cytometry. Caspase-3 and AMD1 were detected in Western blotting. Flow cytometry and Western blotting were also performed after use of siRNA-AMD1-1. Then, analysis AMD1 potential function in cardiotoxicity from bioinformatics techniques including GO, KEGG, PPI, immune infiltration and molecular docking.</p><p><strong>Result: </strong>Maduramicin has myocardial toxic effects in vivo and vitro, which with AMD1 raised. When AMD1 was knocked down, toxic effects of Mad were alleviated. Apoptosis, proliferation and inflammation were the major pathophysiological changes in myocardial apoptosis process with AMD1-knockdown. This process involved in IL1A, IL1B, PTGS2, VEGFA, VEGFC and HBEFG, as hub genes related AMD1 cardiotoxicity function for Maduramicin. AMD1 was knocked down, their microenvironment changes: Effector memory CD4 T cell and Natural killer cell were more infiltrated, and Mast cell were less infiltrated.</p><p><strong>Conclusion: </strong>Mad exerted cardiotoxic effects by upregulating the AMD1 gene, which may be associated with cell apoptosis, proliferation and inflammatory response. AMD1 also had cardiotoxicity function, by the impact of both myocardial cells and the microenvironment they live.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"55"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic role of melatonin on acrylamide-induced neurotoxicity via reducing ER stress, inflammation, and apoptosis in a rat model.","authors":"Yusuf Dag, Serkan Yildirim, Emin Sengul, Furkan Aykurt, Melahat Gok, Ali Cinar","doi":"10.1186/s40360-025-00900-8","DOIUrl":"10.1186/s40360-025-00900-8","url":null,"abstract":"<p><p>This study examined the antioxidant, anti-inflammatory, and neuroprotective effects of melatonin (MEL) against acrylamide (ACR)-induced neurotoxicity in Sprague-Dawley rats. The experimental groups included control, ACR, MEL10+ACR, MEL20+ACR, and MEL20. MEL at doses of 10 and 20 mg/kg, and ACR at 50 mg/kg, were administered intraperitoneally for 14 days. On the 15th day, locomotor activity was assessed, and brain tissues were analyzed biochemically, molecularly, and histopathologically. ACR exposure decreased locomotor activity, increased malondialdehyde (MDA) and reduced glutathione (GSH) levels, indicating oxidative stress, and decreased antioxidant enzyme activities (SOD, GPx, CAT). High-dose MEL (MEL20+ACR) effectively reduced lipid peroxidation and restored antioxidant enzyme activities. MEL treatment also suppressed proinflammatory cytokines (TNF-α, IL-1β, IL-6) and neuronal nitric oxide synthase (nNOS), demonstrating anti-inflammatory effects. Furthermore, MEL mitigated ACR-induced neurotoxicity by reducing acetylcholinesterase (AChE) and monoamine oxidase (MAO) levels. ER stress markers (GRP78, ATF4, ATF6, sXBP1, CHOP) and apoptotic markers (Bax, Caspase-3) were elevated following ACR exposure but were suppressed by MEL. Additionally, MEL reduced ACR-induced increases in 8-hydroxy-2-deoxyguanosine (8-OHdG) and glial fibrillary acidic protein (GFAP), markers of DNA damage and astrocyte activation, respectively. These findings underscore the potential of MEL to counteract ACR-induced neurotoxicity through its comprehensive antioxidant, anti-inflammatory, and neuroprotective actions.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"57"},"PeriodicalIF":2.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of potential molecular subtypes and signatures of thyroid eye disease based on angiogenesis-related gene analysis.","authors":"Zixuan Wu, Jun Peng, Xi Long, Kang Tan, Xiaolei Yao, Qinghua Peng","doi":"10.1186/s40360-025-00880-9","DOIUrl":"10.1186/s40360-025-00880-9","url":null,"abstract":"<p><strong>Background: </strong>Thyroid eye disease (TED) is an autoimmune inflammatory disorder of the orbit, associated with a range of potential clinical sequelae. Tumor cells in TED overexpress pro-angiogenic factors, driving the formation of heterogeneous and immature neovascularization. This dysregulated angiogenesis often leads to a hypoxic microenvironment due to insufficient perfusion. Despite its importance, the role of angiogenesis-related genes (ARGs) in TED pathophysiology remains poorly understood.</p><p><strong>Methods: </strong>To bridge this knowledge gap, our study aimed to identify and validate ARGs implicated in TED using a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 103 known ARGs, we aimed to pinpoint those with potential roles in TED. Advanced methodologies, including GSEA and GSVA, facilitated an in-depth exploration of the biological functions and pathways associated with these ARGs. Further refinement through Lasso regression and SVM-RFE enabled the identification of key hub genes and the evaluation of their diagnostic potential for TED. Additionally, we investigated the relationship between these hub ARGs and relevant clinical parameters. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the six ARGs identified as potentially crucial to TED pathology.</p><p><strong>Results: </strong>Our investigation unveiled six ARGs (CRIP2, DUSP1, CTSL, DOCK5, ERAP1, SCG2) as intimately connected to TED. Functional analyses highlighted their involvement in processes such as response to ameboidal-type cell migration, epithelial cell migration, epithelium migration. Importantly, the diagnostic capabilities of these ARGs demonstrated promising efficacy in distinguishing TED from non-affected states.</p><p><strong>Conclusions: </strong>This study identifies six ARGs as novel biomarker candidates for TED, elucidating their potential roles in the disease's pathogenesis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"53"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative safety signals of dopamine agonists: psychiatric and cardiovascular risks derived from FDA adverse event reporting system (FAERS) data.","authors":"Li Mu, Jing Xu, Xiaomei Ye, Yongxian Jiang, Zhanmiao Yi","doi":"10.1186/s40360-025-00886-3","DOIUrl":"10.1186/s40360-025-00886-3","url":null,"abstract":"<p><strong>Background: </strong>Dopamine receptor agonists (DAs) are widely used as first-line therapeutic agents for Parkinson's disease. However, comparative clinical trials assessing their safety profiles are limited. This study aims to compare adverse event (AE) data across various DAs to inform personalized treatment strategies.</p><p><strong>Methods: </strong>AE reports with DAs as the \"primary suspicion (PS)\" were extracted from the FDA Adverse Event Reporting System (FAERS) database, covering 67 quarters from the second quarter of 2007 to the fourth quarter of 2023. Four disproportionality analysis methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS), were employed to evaluate the risk of AEs.</p><p><strong>Results: </strong>A total of 19,745,533 DA-related AEs reports were analyzed. The six DAs-pramipexole, ropinirole, cabergoline, rotigotine, bromocriptine and apomorphine-generated 269, 246, 202, 163, 146, and 135 preferred terms positive signals, respectively. Non-ergot DAs (pramipexole, ropinirole, rotigotine and apomorphine) were primarily associated with psychiatric disorders and reported more hallucinations than ergot-derived dopamine agonists (ergot-DAs), with ropinirole showing a slightly higher signal intensity than pramipexole (ROR = 15.76 vs. 11.23). Pramipexole demonstrated the most significant signal for impulse control disorders (ICDs). Compared with pramipexole and ropinirole, rotigotine generally exhibits milder signals in terms of psychiatric disorders such as hallucinations, ICDs, and sleep-related AEs. Administration site-related AEs were more prominent in rotigotine and apomorphine users. Ergot-DAs exhibited higher signal intensities for cardiac disorders, with cabergoline also showing a notable signal for amnestic symptoms (ROR = 340.54), which is not mentioned in the drug label.</p><p><strong>Conclusion: </strong>This study elucidates the distinct safety profiles of six DAs. Non-ergot DAs are primarily associated with psychiatric AEs, while administration-related AEs are more notable for rotigotine and apomorphine. Ergot-DAs present a higher risk for cardiac valvulopathies. These findings highlight the importance of individualized treatment considerations in clinical practice, emphasizing the need to formulate appropriate treatment plans on patients' specific conditions.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"54"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Aspirin plus clopidogrel versus cilostazol -based triple antiplatelet therapy in patients with ischemic heart disease undergoing PCI: a systematic review and meta-analysis of randomized controlled trials.","authors":"Ramez M Odat, Mushood Ahmed, Sakhr Alshwayyat, Ayham Mohammad Hussein, Taif Haitham AlSaraireh, Ahmad M Molhem, Ali O Aldamen, Malak Ababneh, Bishr Quwaider, Hritvik Jain, Jehad A Yasin, Hamdah Hanifa, Raheel Ahmed","doi":"10.1186/s40360-025-00891-6","DOIUrl":"10.1186/s40360-025-00891-6","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"52"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A disproportionality analysis of real-world events from the FDA Adverse Event Reporting System (FAERS) for Atezolizumab.","authors":"Zhuoyang Li, Ning Zhu, Yuwei Liu, Yan Yu, Tianhong Wang, Congcong Zou, Siman Wang, Xiaofeng Ou","doi":"10.1186/s40360-025-00879-2","DOIUrl":"10.1186/s40360-025-00879-2","url":null,"abstract":"<p><strong>Background: </strong>An increasing number of clinical studies have highlighted the use of atezolizumab in tumor immunotherapy. However, There is still a lack of comprehensive research on its associated adverse events (AEs). To improve our understanding of its toxicological profile and to provide valuable clinical insights regarding into the effectiveness of immunotherapy, this study utilized data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) to conduct a retrospective analysis of AEs linked to atezolizumab.</p><p><strong>Methods: </strong>We extracted the reports of AEs related to atezolizumab from the FAERS database from the first quarter of 2004 to the first quarter of 2024. We quantified them using the reporting odds ratio (ROR) and proportional reporting ratio (PRR), along with chi-square value (χ²), and conducted systematic classification of the AE signal mining results through SAS 9.4 software.</p><p><strong>Results: </strong>A total of 19,563 valid reports were incorporated, involving 20 distinct system organ class categories. The AEs related to atezolizumab, reported at the preferred term level, mainly encompassed anemia [ROR 2.33, 95% confidence interval (CI) lower limit 2.09, PRR 2.31, χ² 255.977], febrile neutropenia (ROR 2.81, 95% CI lower limit 2.50, PRR 2.79, χ² 333.586), neutrophil count decreased (ROR 2.14, 95% CI lower limit 1.89, PRR 2.13, χ² 150.688), white blood cell count decreased (ROR 2.35, 95% CI lower limit 2.03, PRR 2.34, χ² 136.673), sepsis (ROR 2.21, 95% CI lower limit 1.91, PRR 2.20, χ² 117.741), alanine aminotransferase increased (ALT) (ROR 2.86, 95% CI lower limit 2.44, PRR 2.85, χ² 180.031), and aspartate aminotransferase increased (AST) (ROR 2.79, 95% CI lower limit 2.38, PRR 2.78, χ² 170.955).</p><p><strong>Conclusions: </strong>Apart from various degrees of hepatotoxicity, such as increased ALT and AST, the immune-related hematological toxicity of atezolizumab should also be noted. In clinical practice, healthcare providers should always be vigilant for the occurrence of such medication-related AEs and take measures to enhance the safety of clinical medication use.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"51"},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}