Clinical therapeutics最新文献

{"title":"Characterizing Fenofibrate-Related Renal and Urinary Adverse Events: A Comprehensive Analysis of FDA Adverse Event Reporting System Database","authors":"Li Wang PhD,&nbsp;Xiangyun Jin MS,&nbsp;YanChun Li MS","doi":"10.1016/j.clinthera.2025.09.010","DOIUrl":"10.1016/j.clinthera.2025.09.010","url":null,"abstract":"<div><h3>Purpose</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Findings</h3><div>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; <em>P &lt; 0.</em>001), males have a lower risk (OR = 0.656, 95% CI: 0.444–0.968, <em>P = 0.</em>034).</div></div><div><h3>Implications</h3><div>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.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1149-1154"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","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":"Letter to the Editor Regarding “Real-World Polypharmacy and Drug–Drug Interactions in a Large Cohort of Direct Oral Anticoagulant Users With Atrial Fibrillation”","authors":"Xuezheng Zhu MBBS ,&nbsp;Daquan Liao MBBS ,&nbsp;Shiye Huang MBBS ,&nbsp;Ziye Zhuang MBBS","doi":"10.1016/j.clinthera.2025.10.003","DOIUrl":"10.1016/j.clinthera.2025.10.003","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1180-1181"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430332","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":"FORZINITY (Elamipritide)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.10.004","DOIUrl":"10.1016/j.clinthera.2025.10.004","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1183-1184"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437447","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 ,&nbsp;Hadiseh Mohammadi ,&nbsp;Maryam Teimouri ,&nbsp;Masoud Imani ,&nbsp;Hossein Hosseini","doi":"10.1016/j.clinthera.2025.09.011","DOIUrl":"10.1016/j.clinthera.2025.09.011","url":null,"abstract":"<div><h3>Introduction</h3><div>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<strong>.</strong></div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Our results showed that green tea consumption did not significantly affect FBS (SMD: –0.03; 95%; <em>P = 0.</em>95), HbA1C (SMD: 4.87; 95%; <em>P = 0.</em>63), systolic blood pressure (SMD: -0.42; 95%; <em>P = 0.</em>36), diastolic blood pressure (SMD: –0.24; 95%; <em>P = 0.</em>53), total cholesterol (SMD: –0.38; 95%; <em>P = 0.</em>19), TG (SMD: –0.17; 95%; <em>P = 0.</em>34), HDL-C (SMD: –0.07; 95%; <em>P = 0.</em>75), or LDL-C (SMD: –0.45; 95%; <em>P = 0.</em>25). Subgroup analyses showed that short-term green tea intake (&lt;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.</div></div><div><h3>Conclusion</h3><div>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 (&lt;3000 mg/day), and those with shorter intervention durations (&lt;8 weeks).</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages e1-e9"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","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":"Comparative Effectiveness of Direct-Acting Antiviral Treatment for Hepatitis C Virus Infection on Depressive Symptoms in Patients With Posttraumatic Stress Disorder","authors":"Brian Shiner MD, MPH ,&nbsp;Bradley V. Watts MD, MPH ,&nbsp;Luke Rozema MS ,&nbsp;Jaimie L. Gradus DMSc, DSc, MPH","doi":"10.1016/j.clinthera.2025.09.008","DOIUrl":"10.1016/j.clinthera.2025.09.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Newer medications for Hepatitis C Virus Infection (HCV), called direct acting antivirals (DAAs), are less likely to cause depression than older interferon-containing treatments. However, the risk of exacerbating depression has not been examined in subgroups of patients with pre-existing mental illness. We investigated whether several DAAs for HCV, including glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL), impact depressive symptoms in a population of patients with post-traumatic stress disorder (PTSD).</div></div><div><h3>Methods</h3><div>We developed a retrospective cohort of United States Department of Veterans Affairs (VA) patients with PTSD receiving DAAs for HCV. We measured depressive symptoms before and after DAA treatment using the Patient Health Questionare-9 (PHQ-9), a patient-reported outcome measure with a range of 0-27, a screening threshold of 10 or higher, and a minimal clinically important difference of 5 points. We measured pre/post changes in PHQ-9 score and compared adjusted differences between treatment groups.</div></div><div><h3>Findings</h3><div>Our cohort included 873 patients (GLE/PIB <em>n</em> = 357, LDV/SOF <em>n</em> = 308, SOF/VEL <em>n</em> = 208). Adjusted baseline PHQ-9 scores were consistent with mild depression and similar across groups (10.5 ± 7.2 for GLE/PIB, 10.6 ± 7.2 for LDV/SOF, 10.9 ± 7.2 for SOF/VEL). Adjusted change in PHQ-9 score was minimal and did not differ across groups (-2.0 ± 5.8 for GLE/PIB, -1.1 ± 6.5 for LDV/SOF, -2.2 ± 6.1 for SOF/VEL). The adjusted frequency of 5-pont change was low and did not differ meaningfully across groups (Improvement: 22.4% for GLE/PIB, 18.9% for LDV/SOF, 26.6% for SOF/VEL; Worsening: 9.1% for GLE/PIB, 14.3% for LDV/SOF, 10.1% for SOF/VEL).</div></div><div><h3>Implications</h3><div>DAAs had very little impact on depressive symptoms for VA patients with PTSD and HCV infection.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1137-1142"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205628","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":"Diabetes Mellitus: Promising Clinical Research in a Time of Political Uncertainty","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.10.010","DOIUrl":"10.1016/j.clinthera.2025.10.010","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1089-1090"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562929","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 BPharm ,&nbsp;Yingshi Wang BMed ,&nbsp;Wenwen Zheng MMed ,&nbsp;Junli Wu BMed ,&nbsp;Yufen Shen MMed ,&nbsp;Jianjun Ji MPharm ,&nbsp;Pengfei Du MMed","doi":"10.1016/j.clinthera.2025.09.009","DOIUrl":"10.1016/j.clinthera.2025.09.009","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Findings</h3><div>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.</div></div><div><h3>Implications</h3><div>This study offers an enhanced comprehension of the potential AEs that could be induced by teplizumab, thereby furnishing invaluable insights for its clinical application.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1143-1148"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","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":"Constructive Critique on “Efficacy and Safety of Nintedanib in Japanese Patients With Early-Stage Idiopathic Pulmonary Fibrosis: A One-Year Interim Analysis from a Multicenter Observational Study in Kyushu and Okinawa, Japan”","authors":"Parth Aphale PhD,&nbsp;Himanshu Shekhar BHMS,&nbsp;Shashank Dokania BHMS","doi":"10.1016/j.clinthera.2025.08.009","DOIUrl":"10.1016/j.clinthera.2025.08.009","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1176-1177"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999849","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":"Clinical Study of Cardiac Electrophysiology Affected After Percutaneous Transluminal Septal Myocardial Ablation for Obstructive Cardiomyopathy","authors":"Tianzhu Li MD ,&nbsp;Jinzhao Li MD ,&nbsp;Jun Zhang MD ,&nbsp;Nimin Lu MD","doi":"10.1016/j.clinthera.2025.09.006","DOIUrl":"10.1016/j.clinthera.2025.09.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Hypertrophic cardiomyopathy has an estimated prevalence of approximately 1/200, driven by advancements in genetic testing and high-sensitivity cardiac imaging. This study evaluates the efficacy of percutaneous transluminal septal myocardial ablation (PTSMA) in treating hypertrophic obstructive cardiomyopathy (HOCM) and its impact on cardiac electrophysiology.</div></div><div><h3>Methods</h3><div>A cohort of 38 patients with HOCM, admitted between June 2022 and June 2023, underwent PTSMA. Cardiac function classifications, interventricular septal thickness, left ventricular end-diastolic diameter (LVEDD), left ventricular outflow tract (LVOT) diameter, mitral valve early diastolic velocity (E peak), mitral annular early diastolic velocity (e′), and cardiac electrophysiological parameters (Tp-Te interval and QTcd) were assessed before and 1 month postprocedure.</div></div><div><h3>Findings</h3><div>One month post-PTSMA, significant reductions were observed in cardiac function classification, interventricular septal thickness, and E/e′ ratio (<em>P</em> &lt; 0.05), alongside increases in LVEDD and LVOT diameter (<em>P</em> &lt; 0.05). The Tp-Te interval and QTcd were significantly shortened (<em>P</em> &lt; 0.05).</div></div><div><h3>Implications</h3><div>PTSMA shows potential to improve cardiac function and reduce LVOT obstruction in HOCM patients, with favorable effects on cardiac electrophysiology. However, further multi-center studies with long-term follow-up are required to validate these findings and establish its broader therapeutic role.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1124-1129"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212038","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":"A Novel Metered Dose Inhaler Formulation of Triple-Drug Fixed-Dose Combination of Vilanterol, Glycopyrronium, and Fluticasone Furoate: A Phase III, Randomized, Multicenter Trial to Evaluate the Efficacy and Safety in Indian Patients With Uncontrolled Asthma","authors":"Chintan Patel ,&nbsp;Diptikant Sahoo ,&nbsp;Vaishal Sheth ,&nbsp;Manish Kumar Jain ,&nbsp;Ravi Koppula ,&nbsp;Sanjay Verma ,&nbsp;Deepak Kumar ,&nbsp;Jayanta Kumar Panda ,&nbsp;Deven Parmar ,&nbsp;Kevinkumar Kansagra ,&nbsp;Hardik Pathak","doi":"10.1016/j.clinthera.2025.09.020","DOIUrl":"10.1016/j.clinthera.2025.09.020","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of vilanterol 12.5 µg, glycopyrronium 25 µg, and fluticasone furoate 100 µg (VIL-GLY-FF)–metered dose inhaler (MDI) (developed by M/s. Zydus Healthcare Limited) in comparison with the approved FDC of indacaterol 150 µg, glycopyrronium 50 µg, and mometasone furoate 160 µg (IND-GLY-MF)–dry powder inhaler (DPI) in patients with persistent asthma.</div></div><div><h3>Methods</h3><div>Patients were randomized (1:1) in either the test (VIL-GLY-FF-MDI) or reference (IND-GLY-MF-DPI) group. Fixed-dose combinations were administered once daily for 12 weeks; for VIL-GLY-FF-MDI, patients were instructed to administer TWO actuations at 1 time in a day, doubling the final doses delivered of its components. For IND-GLY-MF-DPI, (Zydus Healthcare Limited, Ahmedabad) patients inhaled 1 capsule via the Respihaler device once daily. The primary objective was to compare the between-group difference in the change in trough forced expiratory volume in 1 second (FEV1) at week 12 from baseline.</div></div><div><h3>Findings</h3><div>A total of 256 patients were enrolled. The change in least square mean (SE) in trough FEV1 at week 12 from baseline was 287.15 (18.00) mL and 284.94 (17.93) mL for the test and reference groups, respectively. For a predefined −150 mL noninferiority margin, 2-sided 95% CIs (−47.83 to 52.26 mL) for the difference in the mean change in trough FEV1 (2.21 mL) between the 2 groups reported the noninferiority of VIL-GLY-FF-MDI to IND-GLY-MF-DPI. The test FDC was well tolerated.</div></div><div><h3>Implications</h3><div>Efficacy and safety of VIL-GLY-FF-MDI were found to be similar to those of IND-GLY-MF-DPI in Indian patients with persistent asthma. Clinical Trial Registry India identifier: CTRI/2024/01/061230.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 12","pages":"Pages 1170-1175"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408467","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}