Clinical Drug Investigation最新文献

{"title":"Correction: Comparison of Pharmacokinetics of Long-Acting Local Analgesics: CPL-01, a Novel Extended-Release Ropivacaine, Demonstrates Consistent and Predictable Exposure Compared with Liposomal Bupivacaine.","authors":"Stevie Pope, Christopher Crean, Sarah Thrasher, Hanghang Xu, P J Chen, Lee Chen, DeeDee Hu, Erol Onel","doi":"10.1007/s40261-025-01431-0","DOIUrl":"https://doi.org/10.1007/s40261-025-01431-0","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tebentafusp Versus Nivolumab Plus Ipilimumab for Metastatic Uveal Melanoma: An E-Value Sensitivity Analysis Assessing Effect of Unmeasured Confounders on Observational Associations.","authors":"Na Zhang, Yu-Wei Qiao, Dan Su, Guo Yu, Guo-Fu Li","doi":"10.1007/s40261-025-01422-1","DOIUrl":"10.1007/s40261-025-01422-1","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"165-168"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Specific Plasma Concentration, Efficacy and Safety of Ciprofol (Cipepofol) for Induction and Maintenance of General Anesthesia in Pediatric Patients Undergoing Elective Surgery: A Single-Arm Prospective, Pragmatic Trial.","authors":"Zheng Chen, Tuochao Peng, Shuibing Zhang, Qiaoyun Yang, Shuangquan Qu, Yong Cao, Junxia Chen, Yiwei Mao","doi":"10.1007/s40261-025-01425-y","DOIUrl":"10.1007/s40261-025-01425-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Ciprofol (Cipepofol) currently has well-established clinical research data in adult Chinese patients, but there is a lack of reliable research data in pediatric patients. This study aimed to assess the age-specific plasma concentration, efficacy and safety profiles of cipepofol in pediatric patients aged 2-17 years during the induction and maintenance of general anesthesia.</p><p><strong>Methods: </strong>This was a single-arm, open-label, prospective, pragmatic study conducted in the Hunan Children's Hospital from May 10, 2023 to August 25, 2023, that involved pediatric patients undergoing elective surgery after the induction and maintenance of general anesthesia. Cipepofol was administered as an intravenous bolus injection of 0.6 mg/kg (patients aged 2-11 years) or 0.5 mg/kg (12-17 years) for induction, followed by an initial maintenance infusion of 1.2 mg/kg/h or 1.4 mg/kg/h, respectively. The primary endpoint-plasma concentration of cipepofol was measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The age-specific plasma concentration, efficacy and safety profiles of cipepofol are summarized using descriptive statistics.</p><p><strong>Results: </strong>All 38 enrolled patients completed the study, including 14 children aged 2-5 years, 12 children aged 6-11 years and 12 children aged 12-17 years. The trends of plasma concentration variations among patients in the three age groups were largely consistent. The success rates of anesthesia induction and maintenance for patients in the three groups were both 100%, and no patients required rescue medication. Children aged 2 to 5 years had the longest median durations of successful anesthetic induction (1.1 min) and eyelash reflection disappearance (1.2 min), while the median durations for patients aged 6-11 years and those aged 12-17 years (0.5 and 0.5 min) were similar. The median time to extubation and length of stay in the post-anesthesia care unit tended to be the longest in children aged 6-11 years (23.5 and 30.0 min) but were comparable for those aged 2-5 years (10.5 min and 20.0 min) and 12-17 years (11.0 and 20.0 min). The median time to full alertness tended to decrease with increasing age (33.7 vs 25.8 vs 22.7 min). A total of 4 (10.5%) patients experienced treatment-emergent adverse events in those aged 2-5 years or 12-17 years, with a severity of grade 1 or grade 2.</p><p><strong>Conclusion: </strong>Cipepofol had good safety for the induction and maintenance of general anesthesia in pediatric patients aged over 2 years. The dosing regimen with an intravenous bolus injection of 0.5 mg/kg for induction, followed by an initial maintenance infusion of 1.4 mg/kg/h was adequate for children aged 12-17 years; age-specific dose regimen for children aged 2-11 years should be improved by further large-scale prospective studies.</p><p><strong>Trial registration: </strong>ChiCTR2400085640, July","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"137-150"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-Dependent Relationship Between Long-Term Metformin Use and the Risk of Diabetic Retinopathy: A Population-Based Cohort Study.","authors":"Yu-Ching Li, Kuang-Hua Huang, Yih Yang, Shuo-Yan Gau, Tung-Han Tsai, Chien-Ying Lee","doi":"10.1007/s40261-025-01421-2","DOIUrl":"10.1007/s40261-025-01421-2","url":null,"abstract":"<p><strong>Background and objective: </strong>Recent research has raised concerns about the association between metformin treatment in patients with diabetes mellitus (DM) and an increased risk of diabetic retinopathy. We sought to investigate this relationship, specifically examining if metformin use affects diabetic retinopathy risk in a dose-dependent manner.</p><p><strong>Methods: </strong>This study was a secondary data analysis based on a nationwide population database in Taiwan. Patients with new-onset DM, an age of 20 years or older, and a diagnosis of type 2 DM received at any time during 2002-2013 were included in the study. Patients diagnosed with new-onset type 2 DM between 2002 and 2013 were enrolled as the study population. We divided them into two groups: those treated with metformin and those treated with sulfonylureas. A Cox proportional hazards model was employed to estimate the risk of diabetic retinopathy after 5 years of follow-up, including cumulative defined daily dose and intensity of metformin treatment.</p><p><strong>Results: </strong>A total of 241,231 patients received treatment with metformin, while 152,617 patients were treated with sulfonylureas. Compared with patients treated with sulfonylureas, patients who received metformin treatment, at a cumulative defined daily dose < 30, had a lower risk of diabetic retinopathy (adjusted hazard ratio = 0.77; 95% confidence interval 0.60-0.98). However, those with varying defined daily doses, especially at a higher metformin treatment level (> 25 defined daily dose), had a 2.43 times higher risk of diabetic retinopathy (95% confidence interval 1.37-4.30) compared with patients treated with sulfonylureas.</p><p><strong>Conclusions: </strong>Patients with DM treated with a lower cumulative dosage of metformin showed beneficial effects that were associated with a lower risk of diabetic retinopathy. In contrast, a higher intensity of metformin use had a greater risk of diabetic retinopathy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"125-136"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406078","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":"Economic Model of Uridine Triacetate Versus Supportive Care for the Treatment of Patients with Life-Threatening Early-Onset Severe Toxicity.","authors":"Jorge J Garcia, Alice Beers, Paige Reid, Salvatore Miragliotta, Suzanne Ward, Setareh A Williams, Michelle Barnard, Megan Bourque, Chantal Trepanier, Amanda Griffin","doi":"10.1007/s40261-025-01426-x","DOIUrl":"10.1007/s40261-025-01426-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Early-onset severe toxicity following the administration of 5-fluorouracil (5-FU) or capecitabine occurs in approximately 10-30% of patients receiving fluoropyrimidine therapy in the USA and is fatal to at least 0.5% of patients treated. Supportive care measures used to manage symptoms of toxicity are associated with extended hospital length of stay, high cost of care, and poor survival. Uridine triacetate is indicated as an emergency treatment for patients who exhibit early-onset, severe or life-threatening toxicity, and has been shown to significantly improve clinical outcomes. Despite its life-saving capability to reverse early-onset severe toxicity, uridine triacetate may be underutilized.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aims to evaluate the economic impact of uridine triacetate as a rescue therapy for adult patients from the US hospital payer perspective for early-onset severe toxicity, who are expected to die without treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A decision tree model was developed to compare inpatient survival, hospital length of stay, and inpatient healthcare resource utilization for patients treated with and without uridine triacetate. Costs associated with hospitalization, including supportive care measures and monitoring were evaluated, considering medications and procedures commonly used to manage various severe toxicities experienced (e.g., gastrointestinal, hematological, etc.). The model compared the hypothetical current practice, in which approximately half of patients expected to die from early-onset severe toxicity receive uridine triacetate in addition to supportive care, with the proposed future practice in which all eligible patients receive uridine triacetate during their hospital stay. Hypothetical practical scenarios for US institutions were also considered.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;For each adult patient hospitalized for early-onset severe or life-threatening toxicity who would be expected to die without treatment, adoption of uridine triacetate as a rescue treatment was associated with clinical benefits, including increased inpatient survival (48.5%) and a 7.3-day reduction in total hospital length of stay per patient. Treatment of each additional patient with uridine triacetate was associated with an incremental cost of US$25,247 per patient. Seventy percent of the drug cost was offset by reduction in inpatient healthcare resources utilization. This cost offset is likely underestimated as it does not include additional savings from potential reimbursements associated with changes in hospital length of stay, readmissions and discounting. Hypothetical scenarios demonstrated that model outputs were most sensitive to changes in length of stay and hospitalization costs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Optimal treatment with uridine triacetate for all hospitalized patients in the USA expected to die from early-onset severe toxicity has the potential to improve ","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"111-123"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476333","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":"Dihydropyrimidine Dehydrogenase Deficiency (DPYD) Genotyping-Guided Fluoropyrimidine-Based Adjuvant Chemotherapy for Breast Cancer. A Cost-Effectiveness Analysis.","authors":"Dina Abushanab, Shaban Mohamed, Rania Abdel-Latif, Diala Alhaj Moustafa, Wafa Marridi, Shereen Elazzazy, Radja Badji, Wadha Al-Muftah, Said I Ismail, Salha Bujassoum, Asma Al-Thani, Daoud Al-Badriyeh, Moza Al Hail","doi":"10.1007/s40261-024-01413-8","DOIUrl":"10.1007/s40261-024-01413-8","url":null,"abstract":"<p><strong>Background and objective: </strong>While standard doses of adjuvant fluoropyrimidine-based chemotherapies are generally safe for most patients, the risk of severe adverse drug reactions (ADRs) is increased for those with dihydropyrimidine dehydrogenase deficiency (DPYD), a genetic variation that affects drug metabolism. The objective of this study was to examine the cost effectiveness of offering DPYD pharmacogenetic-guided care, where genetic testing informs personalized dosing versus the current standard of care (SoC), which involves administering fluoropyrimidine-based therapies without prior genetic screening, for local or metastatic breast cancer patients in Qatar.</p><p><strong>Methods: </strong>We developed a two-stage decision analysis, with an analytic tree model over a 6-month period, followed by a life-table Markov model over a lifetime horizon. We compared the current SoC with the alternate strategy of DPYD genetic screening in patients living in Qatar with local or metastatic breast cancer who were eligible for adjuvant fluoropyrimidine therapy. Clinical outcomes and utilities were obtained from published studies, while healthcare costs were estimated from Hamad Medical Corporation, Qatar. The short-term outcome included the incremental cost-effectiveness ratio (ICER), defined as cost per success (survival without grade III/IV ADRs) at 6 months. The long-term outcome was the ICER, defined as cost per quality-adjusted life year (QALY) gained, with a 3% annual discount rate. The study adopted a public healthcare perspective in Qatar. Sensitivity analyses were conducted to explore the impact of key input parameters on the robustness of the model.</p><p><strong>Results: </strong>In the short-term model, at its base case, DPYD genomic screening was dominant over SoC with a mean cost-saving of QAR84,585 (95% confidence interval [CI], 45,270-151,657). This cost saving reflects the overall economic benefits associated with the implementation of DPYD genomic screening. In the long-term model, compared to the current SoC, DPYD genetic screening would result in an ICER of QAR21,107 (95% CI -59,382-145,664) per QALY gained.</p><p><strong>Conclusion: </strong>Based on our model, implementing DPYD genetic screening to detect DPYD mutations in breast cancer patients before therapy initiation seems to be a cost-saving and cost-effective strategy in Qatar.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"151-163"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064127","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":"The Cost Effectiveness of Adjunctive Medical Cannabis Therapy in the Treatment of Moderate Post-Traumatic Stress Disorder.","authors":"Mitchell L Doucette, Dipak Hemraj, D Luke Macfarlan, Junella Chin, Emily Fisher","doi":"10.1007/s40261-025-01424-z","DOIUrl":"https://doi.org/10.1007/s40261-025-01424-z","url":null,"abstract":"<p><strong>Introduction: </strong>Research on the benefits of medical cannabis (MC) is emerging and supports its use as a treatment for post-traumatic stress disorder (PTSD). This study aimed to evaluate the cost effectiveness of MC as an adjunctive therapy for moderate PTSD under varying reimbursement scenarios.</p><p><strong>Methods: </strong>A cost-utility analysis was conducted from the US payor perspective, using pricing data from the largest multi-state MC producer and established literature on standard PTSD treatments. We analyzed eight MC product types: dried flower, oral solutions, tablets, and edibles, each available in low/moderate (LM) and high-cost formulations. Incremental cost-utility ratios (ICURs) were calculated for these products across reimbursement levels of 100%, 75%, 50%, and 25%. Probabilistic sensitivity analyses with 10,000 Monte Carlo simulations were conducted to assess cost-effectiveness acceptability across willingness-to-pay (WTP) thresholds of $0-$100,000 per quality-adjusted life year (QALY) gained.</p><p><strong>Results: </strong>Non-flower MC products (edibles, oral solutions, and tablets) consistently demonstrated cost-effectiveness under a WTP threshold of $50,000, even at 100% reimbursement. Dried flower products, while less cost effective due to higher costs, achieved cost effectiveness under 75% or lower reimbursement levels for LM cost formulations. Sensitivity analyses confirmed robust ICURs for non-flower products, with narrower variability compared to dried flower products.</p><p><strong>Conclusions: </strong>Medical cannabis products, particularly non-flower formulations, represent a cost-effective adjunctive therapy for moderate PTSD under various reimbursement scenarios. This analysis underscores the importance of evidence-based reimbursement policies to improve patient access to cost-effective treatments while ensuring financial sustainability for payors.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability, and Pharmacokinetics of a Novel Anti-obesity Agent, S-309309, in Healthy Adults with or Without Obesity.","authors":"Toru Ishibashi, Hideki Tanioka, Tatsuya Ikehara, Safwan Kezbor, Takuhiro Sonoyama","doi":"10.1007/s40261-024-01418-3","DOIUrl":"10.1007/s40261-024-01418-3","url":null,"abstract":"<p><strong>Background: </strong>Anti-obesity medications are recommended for patients who do not achieve and maintain weight loss despite lifestyle interventions. S-309309 is a novel oral inhibitor of monoacylglycerol O-acyltransferase 2 being developed as a treatment for obesity.</p><p><strong>Objective: </strong>The objective of the study was to investigate the safety, clinical pharmacology, pharmacokinetics and pharmacodynamic biomarker of S-309309.</p><p><strong>Methods: </strong>A phase I, single-center, two-part, randomized, double-blind, placebo-controlled study of S-309309 following oral administration of a single-ascending dose (part 1) and a multiple dose (part 2) in healthy adults with or without obesity was conducted. We also assessed the effect of food on the pharmacokinetics of S-309309 and the effect of S-309309 on electrocardiogram parameters, the pharmacokinetics of midazolam (a cytochrome P450 3A substrate), and the pharmacodynamic biomarker of monoacylglycerol O-acyltransferase 2 inhibition.</p><p><strong>Results: </strong>In part 1 (N = 50), a single-ascending dose of S-309309 in healthy adults demonstrated dose proportionality and comparable exposure of S-309309 between the fasted and fed states. In part 2 (N = 24), no clinically meaningful difference was observed in the pharmacokinetics of multiple doses between healthy adults with or without obesity. S-309309 did not affect the pharmacokinetics of the cytochrome P450 3A substrate. The pharmacodynamic biomarker of monoacylglycerol O-acyltransferase 2 inhibition, dicarboxylic acid (18:1), was significantly increased after S-309309 administration in healthy adults with or without obesity. Overall, S-309309 demonstrated acceptable safety and tolerability without any serious adverse events or discontinuations because of adverse events, and did not have a clinically relevant effect on the heart rate or cardiac conduction. An effect on the placebo-corrected change-from-baseline corrected QT interval, corrected for heart rate using the Fridericia method, exceeding 10 ms can be excluded.</p><p><strong>Conclusions: </strong>S-309309 was well tolerated as single-dose (up to 300 mg) and multiple-dose (50 mg once daily for 14 days) oral administration. The pharmacokinetic characteristics remained unaffected by obesity and food intake. S-309309 did not affect the pharmacokinetics of the cytochrome P450 3A substrate. Overall, S-309309 had an acceptable safety profile and favorable pharmacokinetic and pharmacodynamic characteristics.</p><p><strong>Clinical trial registration: </strong>NCT05247970, date of registration: 8 February, 2022.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"85-99"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001235","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":"The Cost-Effectiveness of CDK4/6 Inhibitors in Treating HR+/HER2- Metastatic Breast Cancer Patients in the USA: When Non-medication Expenses are Considered.","authors":"Asal Pilehvari, Wen You, Gretchen Kimmick, Fabian Camacho, Gloribel Bonilla, Roger Anderson","doi":"10.1007/s40261-024-01416-5","DOIUrl":"10.1007/s40261-024-01416-5","url":null,"abstract":"<p><strong>Background and objective: </strong>Cyclin-dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy (ET) significantly enhance progression-free survival and overall survival in patients diagnosed with HR+/HER2- metastatic breast cancer (MBC). However, they are highly expensive, and their economic impact has not been fully evaluated. This is a retrospective secondary analysis evaluating the cost effectiveness of these drugs, differentiating between medication-related and non-medication costs from a healthcare perspective.</p><p><strong>Methods: </strong>We identified 3879 patients diagnosed with MBC who received either CDK4/6i+ET (N = 2137) or ET alone (N = 1742) as first-line treatment between February 2015 and November 2021 using a USA-wide electronic health record-derived de-identified database. SEER-Medicare claims spending data were used to quantify monthly costs as a supplement to the database. Relevant costs included prescribed medications (ET and/or CDK4/6i) and overall other costs. The effectiveness was measured as progression-free duration in months. The incremental cost effectiveness ratio (ICER) analysis was conducted to examine the cost effectiveness of first-line CDK4/6i as compared with first-line ET alone.</p><p><strong>Results: </strong>For medication costs, CDK4/6i+ET (mean cost: $240,723.7; mean effect: 19.2 months of delayed progression) compared with ET alone (mean cost: $5159.7; mean effect: 16 months without progression) resulted in an ICER of $73,098 per month of delayed progression. For non-medication costs, CDK4/6i+ET (mean cost: $43,656.6) compared with ET alone (mean cost: $66,083.5) resulted in an ICER of - $7178 per month of delayed progression.</p><p><strong>Conclusion: </strong>The cost of treating HR+/HER2- MBC is driven by the cost of CDK4/6i. Using CDK4/6i+ET reduces non-medication costs compared to ET alone, but these savings are offset by high CDK4/6i medication costs. Lowering the market cost of CDK4/6i or targeting those who can benefit the most could improve the cost effectiveness of CDK4/6i from Medicare perspective.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"59-68"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Real-World Safety of Icosapent Ethyl Versus Omega-3 Polyunsaturated Fatty Acid in Nationwide US Veterans Cohort: Examining Atrial Fibrillation and Bleeding Endpoints.","authors":"Tanvi Patil, Michael Gregory, Natalie Savona, Nabil Jarmukli, Charles E Leonard","doi":"10.1007/s40261-024-01417-4","DOIUrl":"10.1007/s40261-024-01417-4","url":null,"abstract":"<p><strong>Purpose: </strong>The REDUCE-IT randomized trial demonstrated a cardiovascular benefit of icosapent ethyl (IPE) but also raised potential safety signals for atrial fibrillation (AF) and serious bleeding. We aimed to evaluate the real-world safety of IPE versus mixed omega-3 polyunsaturated fatty acid (OM-3) formulations.</p><p><strong>Methods: </strong>This retrospective active comparator new-user cohort study compared rates of new-onset AF and major bleeding (MB) among adult new users of IPE versus OM-3 in 2020-2024 US Veterans Affairs data. Daily drug exposure was determined via prescription dispensing dates. AF and MB outcomes were identified via validated algorithms based on the International Statistical Classification of Diseases and Related Health Problems, 10th revision, clinical modification. Confounding was accounted for via nearest-neighbor pairwise propensity score (PS) matching. The PS, constructed via logistic regression, was informed by expert-identified variables meeting the disjunctive cause criterion. Cox regression was used to estimate adjusted hazard ratios (aHRs), interpretable as average treatment effects for the treated.</p><p><strong>Results: </strong>Cohorts for analyses of AF and MB endpoints included 1927 and 2015 people, respectively, in each of the IPE and OM-3 exposure groups. The median age was 70 years, and the groups exhibited a predominance of white (80%) males (93%). The median follow-up time was 1.29 years per person. Baseline covariates were well balanced by treatment arm after PS matching. Incidence rates for AF were 7.29 versus 7.48 per 100 person-years among new users of IPE versus OM-3. The aHR for AF was 1.15 (95% confidence interval 0.82-1.63). Incidence rates for MB were 3.27 versus 3.35 per 100 person-years among new users of IPE versus OM-3. The aHR for MB was 1.22 (95% confidence interval 0.87-3.02).</p><p><strong>Conclusions: </strong>Our measures of association were consistent with the null, but we were unable to rule out harms from IPE (vs. OM-3) more modest than a 63% increased rate of AF and threefold increased rate of MB.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"69-84"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}