Clinical therapeutics最新文献

{"title":"Addressing Barriers to Inclusive Enrollment in Clinical Trials: Let's Talk About It.","authors":"Jill L Maron","doi":"10.1016/j.clinthera.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.016","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Does a Team Start the Discussion on Inclusion and Diversity in Early-phase Clinical Trials?","authors":"Sheila Mathias, Matthew Barnes","doi":"10.1016/j.clinthera.2025.09.013","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.013","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of a clinical trial is to determine whether a new drug is safe, efficacious, and has fewer side effects than products that may already be on the market. They are essential for ensuring that new potential therapies will advance patient outcomes in some way. This may represent a therapy for a previously untreatable condition, or it may represent an improvement in the efficacy or safety compared with an existing treatment. A new therapy should improve patients' quality of life in a meaningful way, and it should do so for as many potential patients as possible.</p><p><strong>Methods: </strong>To meet this goal, companies should consider the lived experiences and exposures of different populations that are included in the target population for therapies in development. This is why it is generally beneficial to advocate diversity in trials as early as possible in the drug development (Phase I and II trials), as doing so expands the number of trials having inclusivity of racial and ethnic minority groups and are inclusive of more women. Although some improvements in diversity in early-phase trials have been observed in recent years, the overall participation of minority populations in these types of trials continues to be disproportionately lower than their representation in the overall population. In 2023, the minority makeup of the US population was 18.7% Latino and 12.1% Black. In comparison, data reported by the National Cancer Institute in 2023 found the racial makeup in early-phase trials to be 6.9% Latino and 7.1% Black, well below their representation in the larger population.</p><p><strong>Findings: </strong>The authors, who have been involved in numerous clinical trial study design discussions, understand that people from different backgrounds can experience the same disease differently, and thus, it is important to explore these differences in all communities. These differences represent an important consideration in addition to the acknowledged benefit diversity plays to ensure therapies are appropriately tested in the target patient population.</p><p><strong>Implications: </strong>This article explores the need for earlier collaboration/discussion on including diversity in the earlier clinical studies. Our commentary calls for key opinion leaders, study Investigators, study leads, study site recruiters, and coordinators to be open to going beyond the current paradigm of diversity only in pivotal trials, generally Phase III, and explore remedies for inclusion of diversity in early trials.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEPHIENCE (sepiapterin).","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.017","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Pharmacodynamics of a Novel Formulation of Furosemide Administered as a Single Subcutaneous Injection.","authors":"Harry Alcorn, John F Mohr, James E Udelson, Barbara W Cornelius, Michael DiBattista, Phanisyam Kamineni, Taylor Williams, Fadi E Saba","doi":"10.1016/j.clinthera.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.004","url":null,"abstract":"<p><strong>Purpose: </strong>Furoscix (furosemide injection) 80 mg/10 mL is a pH neutral formulation administered subcutaneously (SC) over 5 hours to treat edema in adults with chronic HF or chronic kidney disease. Furosemide 80 mg/mL is a novel concentrated formulation administered as a single 1.0-mL SC injection that could improve convenience for patients. This randomized, open-label, phase 1 study assessed the pharmacokinetics, bioavailability, pharmacodynamics, and safety of furosemide 80 mg/mL SC versus furosemide 80 mg administered intravenously (IV).</p><p><strong>Methods: </strong>Healthy volunteers were randomized 1:1 to furosemide 80 mg/mL SC or furosemide 80 mg IV (two 40-mg boluses, 2 hours apart), and after a 3-day washout, received the opposite treatment. Plasma furosemide pharmacokinetics, urine output, and urinary sodium and potassium excretion were measured through 12 hours post-dose. Bioavailability (the primary endpoint) was assessed as the least-squares mean ratio (LSMR) of area under the curve (AUC) from time 0-last (AUC_last) and 0-infinity (AUC_inf) between furosemide SC and furosemide IV. Plasma furosemide pharmacokinetics were assessed noncompartmentally. Pharmacodynamics were assessed using a repeated measures, mixed model analysis. Safety was assessed through end of study.</p><p><strong>Results: </strong>Twenty-one participants were randomized (furosemide SC/IV, n = 10; furosemide IV/SC, n = 11). The furosemide SC/IV LSMR (90% confidence interval [CI]) AUC_last was 106.1% (102.7%, 109.6%), and LSMR (90% CI) AUC_inf was 107.3% (103.9%, 110.8%). Furosemide 80 mg/mL SC had bioavailability equivalent to furosemide 80 mg IV, as the CIs fell within 80.0%-125.0%. Mean (SD) C_max was 4532.9 (1497.7) ng/mL with furosemide 80 mg/mL SC and 10,087.6 (2804.7) ng/mL with furosemide IV. The therapeutic effects of furosemide 80 mg/mL SC on diuresis, natriuresis, and kaliuresis occurred within 1 hour of treatment and were consistent with those of furosemide IV at all time points. There was no significant difference between furosemide 80 mg/mL SC versus furosemide IV in total urine output or urinary sodium or potassium excretion at 0-6 hours, 0-8 hours, or 0-12 hours. Adverse events (AEs) occurred in 14 (66.7%) participants (furosemide SC, n = 11 [52.4%]; furosemide IV, n = 7 [35.0%]) and were mild or moderate. Ten (47.6%) participants had injection site AEs, all of which were treatment-related, mild, non-serious, and resolved. Injection site pain scores graded on a Likert 11-point scale remained low (mean, <0.4; median, 0) at all time points, were similar between groups, and decreased over time.</p><p><strong>Conclusions: </strong>Furosemide 80 mg/mL SC injection was generally well tolerated and had bioavailability, diuresis, natriuresis, and kaliuresis consistent with those of furosemide IV.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Adverse Events of Teplizumab: A Real-world Pharmacovigilance Study Based on the FDA Adverse Event Reporting System.","authors":"Changjiang Wang, Yingshi Wang, Wenwen Zheng, Junli Wu, Yufen Shen, Jianjun Ji, Pengfei Du","doi":"10.1016/j.clinthera.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.009","url":null,"abstract":"<p><strong>Purpose: </strong>To identify teplizumab-related adverse events (AEs) for type 1 diabetes mellitus from the United States Food and Drug Administration (US FDA) Adverse Event Reporting System database, enhancing the understanding of teplizumab safety in clinical settings.</p><p><strong>Methods: </strong>AEs were extracted from the US FDA Adverse Event Reporting System database spanning from 2004Q1 to 2024Q4. The reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation, neural network, and empirical Bayes geometric mean methods were used to ensure the robustness of the adverse reaction signals.</p><p><strong>Findings: </strong>A total of 847 AEs were identified, and 34 significant disproportionate preferred terms that met the requirements of 4 methods were obtained, involving 9 system categories. The most affected system organ classes were skin and subcutaneous tissue disorders (ROR = 3.24; 95% CI, 2.69-3.9), investigations (ROR = 2.77; 95% CI, 2.30-3.34), gastrointestinal disorders (ROR = 1.83; 95% CI, 1.51-2.21), and general disorders and administration site conditions (ROR = 1.43; 95% CI, 1.21-1.67) ranking by the ROR signal strength. The median time to onset of teplizumab-related AEs was 3.77 days (interquartile range = 0.00-4.00 days), and most AEs occurred within the first 30 days.</p><p><strong>Implications: </strong>This study offers an enhanced comprehension of the potential AEs that could be induced by teplizumab, thereby furnishing invaluable insights for its clinical application.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing Fenofibrate-Related Renal and Urinary Adverse Events: A Comprehensive Analysis of FDA Adverse Event Reporting System Database.","authors":"Li Wang, Xiangyun Jin, YanChun Li","doi":"10.1016/j.clinthera.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.010","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether fenofibrate use is associated with an increased risk of renal and urinary adverse events based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>This retrospective pharmacovigilance study utilized data from the FAERS between January 1st, 2019, and December 31st, 2023. Reports listing fenofibrate as the primary suspect drug were extracted, and renal and urinary adverse events were identified based on preferred terms (PTs) in the MedDRA dictionary. Disproportionality analysis was conducted using four standard algorithms-reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS)-to detect safety signals. The PTs exhibiting positive signals were clinically prioritized, and bivariate logistic regression analysis was performed to identify demographic risk factors associated with serious clinical outcomes.</p><p><strong>Findings: </strong>Between 1 January 2019 and 31 December 2023, a total of 2,810 adverse event reports related to fenofibrate were identified, of which 443 (15.77%) were classified as renal and urinary adverse events. The mean age of affected patients was 57.89 years, with a higher proportion of males (n = 183, 27.94%). Signal detection showed a significant association between fenofibrate and renal and urinary adverse events: ROR = 2.23 (95% CI:2.07-2.41), PRR = 2.18 (χ² = 428.29), IC = 1.12 (IC₀₂₅ = 1.01), EBGM = 2.18 (EBGM05 = 2.04). Adverse events reported with high frequency included acute kidney injury (n = 149, 22.29%), haematuria (n = 88, 13.44%), and urinary tract disorder (n = 82, 12.52%), with acute kidney injury and anuria identified as key clinical priority events. Bivariate logistic regression analysis demonstrated that individuals aged above 65 years had a significantly higher likelihood of experiencing serious clinical outcomes (OR = 2.046, 95% CI: 1.579-3.665; P < 0.001), males have a lower risk (OR = 0.656, 95% CI: 0.444-0.968, P = 0.034).</p><p><strong>Implications: </strong>This study suggests a possible significant association between fenofibrate and renal and urinary adverse events. Safety monitoring and individualized risk assessment of patients using fenofibrate should be enhanced to reduce the risk of potential adverse outcomes.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Green Tea Intake and Metabolic Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials.","authors":"Sahar Ghoflchi, Hadiseh Mohammadi, Maryam Teimouri, Masoud Imani, Hossein Hosseini","doi":"10.1016/j.clinthera.2025.09.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.011","url":null,"abstract":"<p><strong>Introduction: </strong>This review is the first to assess the effects of green tea on blood pressure, lipid profile, and glucose in people with metabolic syndrome, highlighting its potential anti-inflammatory and metabolic benefits.</p><p><strong>Methods: </strong>We used Standardized Mean Differences (SMD) and Cohen's d for group comparisons, while heterogeneity and publication bias were assessed using the I² statistic, Cochrane Q test, Begg's funnel plot, and Egger's test.</p><p><strong>Results: </strong>Our results showed that green tea consumption did not significantly affect FBS (SMD: -0.03; 95%; P = 0.95), HbA1C (SMD: 4.87; 95%; P = 0.63), systolic blood pressure (SMD: -0.42; 95%; P = 0.36), diastolic blood pressure (SMD: -0.24; 95%; P = 0.53), total cholesterol (SMD: -0.38; 95%; P = 0.19), TG (SMD: -0.17; 95%; P = 0.34), HDL-C (SMD: -0.07; 95%; P = 0.75), or LDL-C (SMD: -0.45; 95%; P = 0.25). Subgroup analyses showed that short-term green tea intake (<8 weeks) significantly reduced FBS (SMD: -1.62), total cholesterol (SMD: -1.09), TG (SMD: -0.74), and LDL-C (SMD: -0.83). Doses below 3000 mg/day were also linked to lower total cholesterol (SMD: -0.69) and LDL-C (SMD: -0.83). Among women, green tea improved total cholesterol (SMD: -0.79), HDL-C (SMD: 0.50), LDL-C (SMD: -1.25), and systolic blood pressure (SMD: -1.74), despite overall high heterogeneity and publication bias.</p><p><strong>Conclusion: </strong>Although our results found no significant difference in the measurement factor in patients with MetS. subgroup analyses suggested potential benefits in women, those consuming lower doses (<3000 mg/day), and those with shorter intervention durations (<8 weeks).</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Rosuvastatin/Amlodipine FDC in Patients With Hypertension and Dyslipidemia: A Multicenter, Prospective, Observational Study.","authors":"Jae Hyoung Park, Kyung Hoon Cho, Seong-Il Woo, Seung-Woon Rha, Yun-Hyeong Cho, Kwang Soo Cha, Hong Euy Lim, Wonho Kim, Namho Lee, Seong Wook Cho, Sung Uk Kwon, Shin-Jae Kim, Se Hun Kang, Jin Oh Choi, Jung-Woo Son, Seongwoo Han, Yongwhi Park, Seo-Won Choi, Sangmin Lee, Moo Hyun Kim","doi":"10.1016/j.clinthera.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.012","url":null,"abstract":"<p><strong>Background: </strong>A fixed-dose combination of rosuvastatin and amlodipine (Ros/Aml) offers a simplified approach to simultaneously address hypertension and dyslipidemia. While pivotal trials have demonstrated the efficacy and safety of this regimen, real-world evidence on its clinical outcomes related to major adverse cardiovascular and cerebrovascular events (MACCE) had been limited.</p><p><strong>Methods: </strong>This multicenter, prospective, non-interventional study was conducted across 39 sites in South Korea (2020-2024) to evaluate the 12-month effectiveness and safety of Ros/Aml in adults with coexisting hypertension and dyslipidemia. The primary endpoint was the incidence of MACCE. Secondary endpoints included changes in blood pressure, lipid profiles, and safety outcomes.</p><p><strong>Results: </strong>A total of 5018 patients were enrolled, with 5009 (99.82%) included in the Safety and Efficacy Sets. The mean age was 66.80 years, and 60.39% were male. In the efficacy set, the 12-month MACCE incidence was 0.54% [95% CI: 0.36-0.78], with no significant differences among four dose groups. Ros/Aml significantly reduced systolic and diastolic blood pressure at 6 and 12 months (both P < 0.001), and LDL-C levels (P < 0.0001). Adverse drug reactions were reported in 3.11% of patients; with only 0.06% experiencing serious ADRs and no ADR-related deaths occurred, suggesting a tolerable safety profile.</p><p><strong>Conclusions: </strong>In this large real-world study, Ros/Aml demonstrated a favorable safety profile and was effective in reducing MACCE risk, blood pressure, and lipid levels over 12 months. These findings in patients with hypertension and dyslipidemia support its use as a viable strategy for integrated cardiovascular risk management in clinical practice.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upper Respiratory Tract Infection Associated with Anti-HER2 Antibody Blockade for HER2-Positive Breast Cancer: A Bayesian Disproportionality Analysis Using Data From the FDA Adverse Event Reporting System.","authors":"Jie Zhao, Yang Yang, Xi Chen, Yuan Zhang","doi":"10.1016/j.clinthera.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.015","url":null,"abstract":"<p><strong>Purpose: </strong>The impact of anti-HER2 antibodies and antibody-drug conjugates (ADCs) on adverse events related to upper respiratory tract infection (URTI) in patients with HER2-positive breast cancer (BC) remains inadequately elucidated. This study sought to identify safety signals related to URTI associated with anti-HER2 antibodies and to compare the incidence and severity of these infections among patients treated with various anti-HER2 antibodies. The results may serve as a valuable reference for clinical decision-making.</p><p><strong>Methods: </strong>Medical records of HER2-positive BC patients receiving anti-HER2 treatments from January 2015 to June 2024 were extracted from the Food and Drug Administration (FDA) Adverse Event Reporting System database. The URTI adverse events included nasopharyngitis, URTI, tonsillitis, laryngitis, rhinitis, herpangina, and pharyngitis. Four anti-HER2 treatments were identified: pertuzumab, trastuzumab deruxtecan (T-DXd), trastuzumab, and ado-trastuzumab emtansine (T-DM1). The primary endpoint was the pharmacovigilance (PV) of URTI. The secondary endpoint was the pairwise comparison of the incidence and severity of URTI.</p><p><strong>Findings: </strong>The analysis included 458 reports. For the primary endpoint, the PV signal regarding URTI was detected in the pertuzumab group (ROR = 1.38, 95% CI: 1.16-1.64; IC₀₂₅ = 0.12) and the T-DM1 group (PRR = 2.06, 95% CI: 1.72-2.47; a = 135, χ² = 62.40; ROR = 2.07, 95% CI: 1.72-2.49; IC₀₂₅ = 0.63), whereas no such signal was observed in the trastuzumab and T-DXd groups. For the secondary endpoint, the incidence of URTI was significantly higher in the T-DM1 group than in the trastuzumab (OR = 2.19, 95% CI: 1.74-2.75), pertuzumab (OR = 1.45, 95% CI: 1.15-1.83), and T-DXd (OR = 15.16, 95% CI: 5.77-42.23) groups. The incidence of URTI associated with pertuzumab treatment was notably higher compared to trastuzumab (OR = 1.5, 95% CI: 1.21-1.88) and T-DXd (OR = 10.74, 95% CI: 3.98-28.99) treatments. In comparison to trastuzumab (OR = 8.03, 95% CI: 4.58-14.09), both pertuzumab (OR = 6.37, 95% CI: 3.72-10.93) and T-DM1 were associated with a significant increase in the severity of URTI. However, there was no significant difference in URTI severity between the trastuzumab and pertuzumab treatments.</p><p><strong>Implications: </strong>T-DM1 treatment has a higher possibility for URTI development with higher severity, followed by pertuzumab, trastuzumab, and T-DXd. Patients receiving anti-HER2 antibody treatment, particularly T-DM1, should receive special attention regarding URTI incidence and severity.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world Hepatobiliary Toxicity After Bispecific T-Cell Engager Therapy: A 10-Year Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System and the World Health Organization's Global Individual Case Safety Report Database.","authors":"Rong Hu, Junyi Shen, Peng Luo, Hui Zhang, Yingyi He","doi":"10.1016/j.clinthera.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.001","url":null,"abstract":"<p><strong>Purpose: </strong>Relapsed/refractory hematological malignancies increasingly utilize bispecific T-cell engagers (BiTEs), yet their postmarketing hepatobiliary toxicity profiles remain inadequately characterized. This study aimed to bridge this knowledge gap by conducting the first comprehensive pharmacovigilance analysis of BiTE-associated hepatobiliary toxicity using real-world data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the World Health Organization's global Individual Case Safety Report database (VigiBase).</p><p><strong>Methods: </strong>Hepatobiliary reports were extracted from patients with hematological malignancy deposited in FAERS and VigiBase (2015-2024). Disproportionality analyses, multivariate logistic regression analyses, and time-to-onset analyses were employed to identify safety signals across CD19, non-CD19-targeting BiTE, and non-BiTE receivers, characterize hepatobiliary toxicity, and assess their impact on patients' survival.</p><p><strong>Findings: </strong>Sixteen safety signals emerged, including four previously under-reported adverse events beyond package insert documentation: ascites, hepatobiliary disease, graft-versus-host disease in liver, and veno-occlusive liver disease. This analysis revealed that non-CD19 BiTEs were relatively safe in terms of hepatobiliary toxicities, whereas CD19 BiTE receivers had significantly earlier hepatobiliary toxicity onset (median: 6 vs 14 days; P = 0.002) and higher mortality rate compared with non-BiTE users (OR_FAERS = 3.28 [2.8-3.82]; P_FAERS = 2.05E-16; OR_VigiBase = 3.13 [2.60-3.76]; P_VigiBase = 2.0E-16).</p><p><strong>Implications: </strong>These real-world insights complement clinical trial data; however, the disproportionality analyses employed are susceptible to reporting and utilization biases due to the lack of denominator data. The reported odds ratios and significance should be interpreted as measures of reporting association rather than true risk.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}