Clinical therapeutics最新文献

{"title":"The FDA's Pivotal Role in Global Therapeutic Product Availability.","authors":"Lawrence Liberti, Eunjoo Pacifici","doi":"10.1016/j.clinthera.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.007","url":null,"abstract":"<p><p>Since its inception over a century ago, the U.S. Food and Drug Administration (FDA) has been recognized as the gold standard for assessing the quality, safety, and efficacy of therapeutics. Its scientific expertise and regulatory agility have been applied to a wide range of products, including small molecules, biologics, vaccines, and medical devices. The FDA's global leadership was evident during the COVID-19 pandemic, as it expedited the development and approval of vaccines while maintaining standards for quality, safety, and effectiveness. The FDA serves both domestic and international missions. As the primary approver of most new medicines, it ensures the timely availability of innovative therapeutics for the American public. Moreover, its longstanding leadership in regulatory activities has established it as an international paragon upon which regulatory authorities serving hundreds of millions of people rely. The FDA must maintain its position as the global leader in biopharmaceutical and medical device assessments. This is essential for preserving public health in the U.S., playing a crucial role in fostering bio-innovation and the economic viability of the pharmaceutical sector, and facilitating the global availability of innovative products to benefit worldwide public health.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086004","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":"Qfitlia (fitusiran).","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076432","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":"Association Between Anticoagulants and Interacting Drugs and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation: Case-Control Study in SIDIAP, Catalonia, Spain.","authors":"M Giner-Soriano, L A Carrasco-Ribelles, S Fernández-García, J Castel Llobet, G Cereza García, R Morros","doi":"10.1016/j.clinthera.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.003","url":null,"abstract":"<p><strong>Purpose: </strong>Interactions with anticoagulants causing an increase in their effect may potentially enhance the bleeding risk. We aimed to analyze the risk of major hemorrhage in anticoagulated patients simultaneously exposed to potentially interacting drugs which may enhance the bleeding risk.</p><p><strong>Methods: </strong>Case-control study nested in a cohort of anticoagulated patients in 2011-2020. Cases were all people hospitalized for a major hemorrhage (cerebral or gastrointestinal), matched to individuals without bleeding. The index date was the day of hospital admission for cases and the same date for the matched controls.</p><p><strong>Data sources: </strong>SIDIAP database, containing information from primary health care electronic records, and the database of diagnoses at hospital discharge in Catalonia, Spain. We analyzed exposure to interacting drugs during 3 months prior to the index date. The association between hemorrhage and exposure to interacting drugs was calculated through multivariate logistic regression models.</p><p><strong>Findings: </strong>We included 2,811 cases (77.9% cerebral and 22.1% gastrointestinal hemorrhages), matched to 28,054 controls. We found association between hemorrhage in patients receiving vitamin K antagonists (OR 1.30, 95% CI 1.16-1.47). All types of interactions resulted in higher bleeding risk for all anticoagulants. Proton pump inhibitors were found protective for gastrointestinal (OR 0.55, 95% CI 0.46-0.65) but not for cerebral bleeding (OR 1.18, 95% CI 1.08-1.30).</p><p><strong>Implications: </strong>We estimated the risk of major hemorrhage in anticoagulated patients simultaneously exposed to potentially interacting drugs which may enhance bleeding risk. Our study underscores the potential impact of interactions on cerebral and gastrointestinal bleeding risk in anticoagulated patients.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989273","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 US Supreme Court Joins the Debate Over Gender Dysphoria.","authors":"Marcia M Boumil, Paul Beninger","doi":"10.1016/j.clinthera.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.004","url":null,"abstract":"<p><p>US v. Skrmetti is a legal case currently pending before the US Supreme Court that addresses the constitutionality of a Tennessee statute that prohibits gender-affirming medical care for transgender individuals who have not yet reached the legal age of adulthood, and who are diagnosed with gender dysphoria. Twenty-five other states have similar bans that apply to adolescents diagnosed with gender dysphoria, who are seeking treatment recommended by a physician and who are supported by their parents. Treatment involves gonadotropin-releasing hormone agonists, such as leuprolide or histrelin, which are approved by the Food and Drug Administration for use in children with central precocious puberty and are commonly prescribed off-label for adolescents. The purpose of puberty-blocking drugs is to suppress the onset of hormonal changes of puberty to facilitate the youth's anticipated transgender transition when the youth does reach the legal age of adulthood. Certainty about the time available for a youth to consider their gender identity, with the guidance of a professional support team, minimizes the risk of disruptive anxiety that's associated with near-term onset of sexual maturation involving development of irreversible secondary sex characteristics. This Commentary presents the legal arguments in the case and discusses relevant medical literature on this important issue in anticipation of the US Supreme Court's decision on the Tennessee law.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985846","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":"Duodenal Ulcer in a Child With Cystic Fibrosis on Elexacaftor-Tezacaftor-Ivacaftor Therapy: A Casual Association or a Possible Adverse Event?","authors":"Vito Terlizzi, Martina Di Benedetto, Sara Renzo, Valeria Galici, Luca Scarallo, Jochen G Mainz, Paolo Lionetti","doi":"10.1016/j.clinthera.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.002","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983307","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":"Prescription of Pharmacologic Venous Thromboembolism Prophylaxis Upon Hospital Discharge After Surgery for Lower Limb Fracture-A 3-Center Study in the North-West of England.","authors":"Fatima Kayali, Hritik Nautiyal, Jonathan Topping, Chea Tze Ong, Emadeldin M Ahmed, Martin Sharrock, Jenny Oakley, Makaram Srinivasan, Kuntal Patel, Amit Shah, Paul M Sutton, Charalambos P Charalambous","doi":"10.1016/j.clinthera.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.04.001","url":null,"abstract":"<p><strong>Purpose: </strong>The risk of venous thromboembolism (VTE) after surgery for lower limb trauma may be reduced with pharmacologic prophylaxis upon hospital admission and hospital discharge. To determine the rate and duration of prescription of VTE pharmacologic prophylaxis upon hospital discharge in patients who have surgery for a lower limb fracture.</p><p><strong>Methods: </strong>Retrospective analysis of patients who had surgery for a lower limb fracture at 3 National Health Trust hospitals in the North-West of England.</p><p><strong>Findings: </strong>Data from 127 patients were collected. All patients were prescribed pharmacologic VTE prophylaxis upon hospital admission, and 125 (98%) upon discharge, with 91.3% of patients discharged with low-molecular weight heparin. There was substantial variation in the duration of pharmacologic VTE prescription upon hospital discharge, with a median duration of 42 days (interquartile range, 28-42 days; range, 1-84 days). In our cohort, 7 (5.5%) of patients were prescribed VTE prophylaxis for less than 14 days, and 30(23.6%) prescribed for less than 35 days.</p><p><strong>Implications: </strong>This study reported that pharmacologic prophylaxis for VTE was prescribed for almost all patients upon hospital discharge. However, there was substantial variation in the duration of the prescribed prophylaxis upon hospital discharge, with almost a quarter of patients prescribed less than 35 days. National level prescription guidance for VTE prophylaxis upon hospital discharge may improve consistency within and between centers.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971672","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":"Improved Liver Fibrosis Regression After Direct-Acting Antiviral Therapy in Hepatitis C Patients: A Comparison of Patients With and Without MASLD.","authors":"Alexis McCary, Yi-Shin Sheu, Karen Chesbrough, M Cabell Jonas","doi":"10.1016/j.clinthera.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.03.011","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic Hepatitis C (CHC) often results in liver fibrosis. Therefore, an important benefit of CHC treatment with direct-acting antiviral (DAA) medication is liver fibrosis regression. However, it is unclear how concurrent liver steatosis affects fibrosis regression following DAA therapy. Recent guidelines have defined liver steatosis associated with metabolic syndrome as metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to examine the association of MASLD with the fibrosis regression benefits of DAA treatment for CHC.</p><p><strong>Methods: </strong>We conducted an observational retrospective analysis using electronic health records of patients aged 18-65 who completed DAA therapy for CHC from 2016 through 2022. FIB-4 scores were calculated during three time periods: just prior to DAA initiation, within 6 months post-DAA completion, and within 6-12 months post-DAA completion. These scores categorized liver fibrosis as high risk (>3.25), intermediate risk (1.45-3.25), or low risk (<1.45). An ordinal logistic regression model assessed the degree of fibrosis regression across these periods in CHC patients with and without MASLD.</p><p><strong>Findings: </strong>We identified 845 patients with CHC who received DAA therapy, of whom 225 met MASLD criteria. Both CHC patients with and without MASLD exhibited a decrease in FIB-4 category (coefficient = -0.361, P < 0.001) within the year following DAA therapy. The reduction in FIB-4 category post-treatment was more pronounced in the MASLD group compared to the non-MASLD group, as evidenced by a significant interaction between group and time period (coefficient = -0.439, P = 0.004).</p><p><strong>Implications: </strong>In our cohort, MASLD was associated with greater liver fibrosis regression in the year following DAA therapy for CHC. This suggests that the concurrent presence of MASLD is not associated with diminished fibrosis regression from DAA therapy. Additional research is needed to determine the exact mechanism responsible for DAA-associated fibrosis regression in patients with MASLD.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971642","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":"Mycobacterium tuberculosis: A Resurgent Scourge Writing Another Chapter in Its History","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.03.013","DOIUrl":"10.1016/j.clinthera.2025.03.013","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 403-404"},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903958","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":"Pharmacokinetic/Pharmacodynamic Analysis of Extended/Two-Step Infusion Ceftazidime/Avibactam in Children With Gram-Negative Bacterial Infections","authors":"Ruiying Han MPharm,&nbsp;Ying Zhang BPharm,&nbsp;Baosen Yue MPharm,&nbsp;Yuan Zhi BPharm,&nbsp;Weihua Zhang MPharm,&nbsp;Dan Sun MPharm","doi":"10.1016/j.clinthera.2025.03.008","DOIUrl":"10.1016/j.clinthera.2025.03.008","url":null,"abstract":"<div><h3>Purpose</h3><div>To simulate the pharmacokinetic/pharmacodynamic (PK/PD) exposure of ceftazidime/avibactam (CZA) in children with gram-negative bacterial infections, and explore the appropriateness of the CZA standard dosing regimen (STD), further optimize the dosing regimen by extended/two-step infusion.</div></div><div><h3>Methods</h3><div>Monte Carlo simulations were performed to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) of CZA with varying weight in two age groups (≥6–12 and ≥12–18 years old, respectively), utilizing PK parameters and PD data (from the EUCAST as well as the published data on US children). The simulated dosing regimens included STD and extended/two-step infusion.</div></div><div><h3>Findings</h3><div>When the PK/PD target for ceftazidime was set at 50% of time that free drug concentrations remain above the minimum inhibitory concentration of the pathogen during the dosing interval (50% <em>f</em>T &gt; MIC), the CZA STD achieved PTAs of ≥90% at susceptibility breakpoint (MIC = 8 mg/L) for children in weighed 15–30 kg (≥6–12years old) and 35–45 kg (≥12–18 years old). However, when the PK/PD target for ceftazidime was set at 100% <em>f</em>T &gt; MIC, none could achieve PTAs of ≥90%. The CFR results showed that the STD couldn't provide CFRs ≥90% in all children, but extended infusion or two-step infusion could achieve the target CFRs in all children based on the MIC distribution of US children, and improve the CFRs based on EUCAST's MIC distribution. Compared with extended infusion, two-step infusion could reduce total infusion time in partial patients.</div></div><div><h3>Implications</h3><div>The current STD of CZA may not adequately meet the therapeutic requirements in children, thus it is recommended to optimize the dosing regimen by extended/two-step infusion or increasing the daily dose, guided by therapeutic drug monitoring.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 412-419"},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903959","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 Canadian Real-World Study of Fixed-DOSE combination of Halobetasol Propionate 0.01%/Tazarotene 0.045% Lotion for the Treatment of Moderate-to-Severe Plaque Psoriasis","authors":"R Vender MD ,&nbsp;C Lynde MD ,&nbsp;V Prajapati MD ,&nbsp;R Zeinab PhD ,&nbsp;M Legault PhD ,&nbsp;HC-H Hong MD ,&nbsp;M Barakat MD PhD","doi":"10.1016/j.clinthera.2025.03.005","DOIUrl":"10.1016/j.clinthera.2025.03.005","url":null,"abstract":"<div><h3>Background</h3><div>A fixed-dose combination of HP/TAZ has demonstrated efficacy with a favorable safety profile for treating moderate-to-severe plaque psoriasis.</div></div><div><h3>Objective</h3><div>The present single-arm, open-label study evaluated the use of HP/TAZ in real-world practice.</div></div><div><h3>Methods</h3><div>Adults with moderate-to-severe psoriasis were enrolled and treated with HP/TAZ according to the Canadian label. The primary endpoint was the percentage of patients with treatment success at week 8, defined as an Investigator's Global Assessment score of clear or almost clear with a minimum 2-grade improvement.</div></div><div><h3>Results</h3><div>202 patients received at least one dose of HP/TAZ, 138 patients had efficacy assessments at baseline and week 8. Treatment success was achieved by 26.1% and 43.5% of patients (week 4 and 8 respectively) . Patient-rated average and worst itch were 4.5 and 5.3 points at baseline, with a subsequent reduction to 1.7 and 2.1 points, respectively, at week 8. Patients were satisfied-very satisfied with the HP/TAZ. Application site reactions (13.4%) and dermatitis/eczema (3.5%) were the most frequently reported adverse events (mild-moderate in severity) .</div></div><div><h3>Limitations</h3><div>The study design may limit generalizability of the results as an open label real world evidence study lacking a placebo or comparator arm.</div></div><div><h3>Conclusion</h3><div>Results confirm that HP/TAZ can be beneficial moderate-to-severe psoriasis patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 6","pages":"Pages 445-449"},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903279","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}