Clinical therapeutics最新文献

{"title":"One-year Efficacy and Safety of Dulaglutide in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Study of Asian Patients","authors":"Myung Jin Kim ,&nbsp;Hwi Seung Kim ,&nbsp;Yun Kyung Cho ,&nbsp;Chang Hee Jung ,&nbsp;Woo Je Lee","doi":"10.1016/j.clinthera.2024.06.024","DOIUrl":"10.1016/j.clinthera.2024.06.024","url":null,"abstract":"<div><h3>Purpose</h3><p>Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys and has proven efficacy and safety in patients with diabetic kidney disease. We aimed to evaluate the 1-year efficacy of dulaglutide in patients with diabetic kidney disease who have used the drug for more than 1 year.</p></div><div><h3>Methods</h3><p>This retrospective, observational study comprised 131 patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m² who had received dulaglutide for more than one year between June 2016 and May 2023. The primary outcome measures were changes in glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight from baseline to the 12-month follow-up, with assessments performed at six-month intervals. Subgroup analyses were conducted based on age, sex, baseline body mass index, FPG, and HbA1c, and insulin administration at baseline and last follow-up.</p></div><div><h3>Findings</h3><p>The mean age was 60.0 ± 10.2 years, and 61.1% of the participants were males. Baseline HbA1c, FPG, and body weight were 9.1% (76.0 mmol/mol), 186.8 mg/dL, and 79.3 kg, respectively. Dulaglutide significantly reduced HbA1c, FPG, and body weight from baseline to the 12-month follow-up (mean ± standard error: –1.2 ± 0.1%, –34.8 ± 6.9 mg/dL, and –2.3 ± 0.5 kg, respectively; <em>P</em> &lt; 0.001). Subgroup analysis revealed significant differences in HbA1c reduction based on baseline HbA1c.</p></div><div><h3>Implications</h3><p>Dulaglutide exhibited sustained glucose-lowering and weight-reduction effects during the initial 1 year of treatment in patients with diabetic kidney disease. Altogether, dulaglutide could serve as a favorable long-term therapeutic option for patients with diabetic kidney disease in real-world clinical settings.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001991/pdfft?md5=1b57d901e8f076c7a69335f164773cda&pid=1-s2.0-S0149291824001991-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-controlled Study","authors":"Yun Kyung Cho MD, PhD ,&nbsp;Kyung-Soo Kim MD, PhD ,&nbsp;Byung-Wan Lee MD, PhD ,&nbsp;Jun Hwa Hong MD, PhD ,&nbsp;Jae Myung Yu MD, PhD ,&nbsp;Soo Lim MD, PhD ,&nbsp;Ye An Kim MD, PhD ,&nbsp;Chang Beom Lee MD, PhD ,&nbsp;Sang Soo Kim MD, PhD ,&nbsp;Soo Heon Kwak MD, PhD ,&nbsp;Woo Je Lee MD, PhD","doi":"10.1016/j.clinthera.2024.06.023","DOIUrl":"10.1016/j.clinthera.2024.06.023","url":null,"abstract":"<div><h3>Purpose</h3><p>The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin.</p></div><div><h3>Methods</h3><p>In this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA_1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA_1c from baseline at 24 weeks across the groups.</p></div><div><h3>Findings</h3><p>For the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA_1c of 7.9%. After 24 weeks, HbA_1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of −0.38% and −0.83%, respectively, compared with the PBO group. The proportion of patients with HbA_1c levels &lt;7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone.</p></div><div><h3>Implications</h3><p>The addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. ClinicalTrials.gov identifier: NCT04885712.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S014929182400198X/pdfft?md5=2c1571fd29a2772f3a3996351852b070&pid=1-s2.0-S014929182400198X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Propolis Consumption on Glycemic Indices and Liver Enzymes in Adults: A Grading of Recommendations Assessment, Development, and Valuation-assessed Systematic Review and Dose-Response Meta-analysis","authors":"Shaghayegh Adeli MSc ,&nbsp;Mahsa Maroofi MSc ,&nbsp;Fatemeh Pourteymour Fard Tabrizi Ph.D ,&nbsp;Beitullah Alipour Ph.D ,&nbsp;Marzieh Heidari MSc ,&nbsp;Mahdi Vajdi Ph.D ,&nbsp;Mahdieh Abbasalizad-Farhangi Ph.D","doi":"10.1016/j.clinthera.2024.06.022","DOIUrl":"10.1016/j.clinthera.2024.06.022","url":null,"abstract":"<div><h3>Purpose</h3><p>Even though various randomized controlled trials (RCTs) have assessed the effect of propolis on glycemic indices and liver enzyme concentrations in adults, results have been inconsistent, without conclusive evidence. This systematic review and meta-analysis of RCTs sought to evaluate the effects of propolis consumption on glycemic indices and liver enzymes, fasting blood glucose, insulin, homeostatic model assessment of insulin resistance, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase in adults.</p></div><div><h3>Methods</h3><p>Two independent researchers systematically searched PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library for English-language RCTs published up to April 2024. The results were generated through a random-effects model and presented as the weighted mean difference (WMD) with a 95% CI. The Cochrane Risk of Bias Tool for RCTs and Grading of Recommendations Assessment, Development, and Evaluation assessment were used to evaluate quality assessment and certainty of evidence.</p></div><div><h3>Findings</h3><p>A total of 21 RCTs were included. A pooled analysis of 24 trials reported that propolis consumption led to a significant reduction in fasting blood glucose (WMD, −9.75 mg/dL; 95% CI, −16.14 to −3.35), insulin (WMD, −1.64 µU/mL; 95% CI, −2.61 to −0.68), glycosylated hemoglobin (WMD, −0.46%; 95% CI, −0.71 to −0.21), homeostatic model assessment of insulin resistance (WMD, −0.54; 95% CI, −0.98 to −0.09), alanine transaminase (WMD, −2.60 IU/L; 95% CI, −4.58 to −0.61), and aspartate aminotransferase (WMD, −2.07 IU/L; 95% CI, −3.05 to −1.09). However, there were no significant effects on gamma-glutamyl transferase in comparison with the control group.</p></div><div><h3>Implications</h3><p>This meta-analysis has shown that propolis supplementation may have beneficial effects on glycemic indices and liver enzymes. Future high-quality, long-term RCTs are needed to confirm our results. ClinicalTrials.gov identifiers: CRD42024524763. (<em>Clin Ther</em>. 2024;46:XXX–XXX) © 2024 Elsevier HS Journals, Inc.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888717","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":"Proton Pump Inhibitors Versus Histamine-2 Receptor Blockers for Stress Ulcer Prophylaxis on In-hospital Mortality Among Intensive Care Unit Patients Hospitalized for Major Adverse Cardiovascular and Cerebrovascular Events: Retrospective Cohort Study","authors":"Lanxiang Pu PhD ,&nbsp;Ting Jia MSc ,&nbsp;Shili Su MSc ,&nbsp;Liang Yang MSc ,&nbsp;Hong Yao MSc ,&nbsp;Yujie Su MSc ,&nbsp;Zhaowen Chen","doi":"10.1016/j.clinthera.2024.06.020","DOIUrl":"10.1016/j.clinthera.2024.06.020","url":null,"abstract":"<div><h3>Purpose</h3><p>Patients in the intensive care unit (ICU) commonly receive stress ulcer prophylaxis drugs, either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). The goal of this research was to evaluate the impact of these drugs on mortality among ICU patients hospitalized for major adverse cardiovascular and cerebrovascular events (MACCEs).</p></div><div><h3>Methods</h3><p>ICU patients hospitalized for MACCEs were sourced from the Medical Information Mart for Intensive Care-III database. We performed a propensity score matching analysis to match patients treated with PPIs to those treated with H2RBs for stress ulcer prophylaxis. The outcome was 90-day mortality. We used multivariable Cox regression analyses to compare the effect. Hazard ratio (HR), 95% CIs, and <em>P</em> values were reported from the model.</p></div><div><h3>Findings</h3><p>From 2001 to 2012, a total of 3577 patients hospitalized for MACCEs (1997 received PPIs and 1580 received H2RBs) were admitted. The 90-day mortality was 23.7% (848/3577); it was 27% (540/1997) and 19.5% (308/1580) for PPIs and H2RBs users, respectively. The PPI group exhibited a greater 90‑day mortality in comparison to the H2RBs group (relative risk = 1.17; <em>P</em> = 0.036), after conditioning on potential confounder. The results remained robust in propensity score matching, sensitivity analyses, and subgroup analyses.</p></div><div><h3>Implications</h3><p>PPIs for stress ulcer prophylaxis were linked to an increased risk of in-hospital mortality than H2RBs in patients hospitalized for MACCEs. Further investigation of this association and validation of its clinical significance is needed.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0149291824001954/pdfft?md5=372d0f6ba5c9f0036891b7b1ede02a83&pid=1-s2.0-S0149291824001954-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Landscape of Blood-based Screening Assays After the Fallacy of Theranos, Inc","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2024.08.005","DOIUrl":"10.1016/j.clinthera.2024.08.005","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105141","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":"Racial Comparison of the Pharmacokinetics and Safety of Fixed-dose Combination of Dapagliflozin/Sitagliptin in Western and Korean Healthy Adults","authors":"Pradeep B. Lukka PhD ,&nbsp;Weifeng Tang PhD ,&nbsp;Ann Hammarstedt PhD ,&nbsp;Tom Conrad PhD ,&nbsp;Maria Heijer MSc ,&nbsp;Cecilia Karlsson MD, PhD ,&nbsp;David W. Boulton PhD","doi":"10.1016/j.clinthera.2024.07.007","DOIUrl":"10.1016/j.clinthera.2024.07.007","url":null,"abstract":"<div><h3>Purpose</h3><p>We evaluated the pharmacokinetics, safety, and tolerability of a fixed-dose combination (FDC) of dapagliflozin/sitagliptin versus individual component (IC) tablets in healthy Western and Korean participants. The combination of these antihyperglycemic drugs provides efficient glucose control, and the use of FDC has generally been shown to improve medication adherence in individuals with type 2 diabetes mellitus (T2DM).</p></div><div><h3>Methods</h3><p>Two randomized, open-label, two-period, two-treatment, single-dose, single-center, crossover bioequivalence studies conducted on healthy fasted German participants (aged 18–55 years; Western study) and South Korean participants (aged 19–55 years; Korean study) were included. In both studies, pharmacokinetic parameters (maximum [peak] plasma concentration [C_max], area under the plasma concentration–time curve from zero to the last quantifiable concentration [AUC_last], and area under the plasma concentration–time curve from zero to infinity [AUC_inf]) were used to assess the bioequivalence of 10 mg dapagliflozin/100 mg sitagliptin FDC (Treatment A) with their ICs (Treatment B) under fasted conditions. Safety and tolerability were assessed throughout the study.</p></div><div><h3>Findings</h3><p>Forty-six healthy participants (male, 60.9%; mean age, 39.5 years; mean body mass index [BMI], 23.9 kg/m²) were randomized in the Western study, and 51 healthy participants (male, 100.0%; mean age, 24.6 years; mean BMI, 23.9 kg/m²) were randomized in the Korean study. In both studies, the participants were randomized 1:1 into treatment sequence AB and treatment sequence BA. Dapagliflozin/sitagliptin FDC was bioequivalent to IC tablets in both Western and Korean studies, as the 90% confidence interval of the FDC to IC ratios of the geometric least-squares means of the pharmacokinetic parameters for both dapagliflozin and sitagliptin was within the 0.8000–1.2500 bioequivalence criterion limit. The observed differences in pharmacokinetic parameters, such as C_max, AUC_last, and AUC_inf, between the Western and Korean studies were not clinically meaningful. Dapagliflozin/sitagliptin FDC and their ICs were well tolerated, with no serious adverse events reported in any of the study populations.</p></div><div><h3>Implications</h3><p>The 10 mg dapagliflozin/100 mg sitagliptin FDC and IC formulations were bioequivalent in fasted healthy Western and Korean participants, with no new safety concerns identified, thus offering a useful alternative for patients currently receiving individual medications as part of their treatment regimen.</p></div><div><h3>Clinical trial registration</h3><p>Western study (clinicaltrials.gov: NCT05266404) and Korean study (clinicaltrials.gov: NCT05453786).</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046387","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":"Aspirin and Ticagrelor Versus Aspirin and Clopidogrel or Prasugrel and the Effect on Staphylococcal-associated Infections: A Real-world Study","authors":"Hani Essa MD ,&nbsp;Wern Yew Ding PhD ,&nbsp;Faraz Rana MD ,&nbsp;Sizheng Steven Zhao PhD ,&nbsp;Matthew Anson MBBS ,&nbsp;Philip Austin MRes ,&nbsp;Gema Hernández ,&nbsp;Pankaj Lal MD ,&nbsp;Gregory Y.H. Lip MD ,&nbsp;Uazman Alam PhD","doi":"10.1016/j.clinthera.2024.07.001","DOIUrl":"10.1016/j.clinthera.2024.07.001","url":null,"abstract":"<div><h3>Purpose</h3><p>Antiplatelet therapy is used for the primary and secondary prevention of thrombotic diseases such as acute coronary syndrome (ACS). These patients are more vulnerable to infections, as such, strategies are required to mitigate these risks.</p></div><div><h3>Methods</h3><p>We conducted a retrospective cohort study using TriNetX, a global federated health research network that includes both inpatient and outpatient electronic medical records from health care organizations worldwide. Patients ≥18 years old, after ACS, who were placed on aspirin and ticagrelor were compared with patients placed on aspirin and clopidogrel or prasugrel. Patients were identified using International Statistical Classification of Diseases and Related Health Problems terminology codes. After propensity score matching (1:1), a total of 239,358 patients were identified in each cohort. The primary outcomes of interest investigated were rates of (1) acute and subacute infective endocarditis, (2) sepsis of unknown origin, (3) staphylococcus arthritis, (4) cellulitis and acute lymphangitis, (5) <em>Staphylococcus aureus</em> bacteremia, and (6) staphylococcal pneumonia after initiation of treatment. Outcomes were analyzed at 1, 3, and 5 years.</p></div><div><h3>Findings</h3><p>At 5 years, a combination of aspirin and ticagrelor, compared with a combination of aspirin and clopidogrel or prasugrel, was associated with significantly reduced rates of (1) acute and subacute endocarditis (hazard ratio [HR] plus 95% CI) (HR = 0.85; 0.77–0.945; <em>P =</em> 0.030), (2) sepsis of unknown origin (HR = 0.89; 95% CI, 0.86–0.91; <em>P</em> &lt; 0.0001), (3) cellulitis and acute lymphangitis (HR = 0.89; 95% CI, 0.87–0.92; <em>P &lt;</em> 0.0001, and (4) <em>Staphylococcus aureus</em> bacteremia (HR = 0.72; 95% CI, 0.61–0.85; <em>P =</em> 0.0007). However, a combination of aspirin and clopidogrel was associated with a marinally lower risk of staphylococcal pneumonia (HR = 1.04; 95% CI, 1.01–1.062; <em>P &lt;</em> 0.0001).</p></div><div><h3>Implications</h3><p>A combination of aspirin and ticagrelor is associated with a lower rate of a variety of bacterial infections. This combination warrants further investigation in <em>in-vitro</em> studies to tease out mechanisms and through clinical randomized trials in groups who have ACS and are at high infection risk.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995475","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":"Cost-effectiveness of Azvudine for High-risk Outpatients with Mild-to-moderate Coronavirus Disease 2019 in China","authors":"Hui Yang MD ,&nbsp;Zhaojian Wang MPharm ,&nbsp;Chunping Wang MS ,&nbsp;Ying Zhang MPharm ,&nbsp;Sheng Han PhD ,&nbsp;Zhuoling An PhD","doi":"10.1016/j.clinthera.2024.07.009","DOIUrl":"10.1016/j.clinthera.2024.07.009","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to evaluate the cost-effectiveness of Azvudine for the treatment of mild-to-moderate coronavirus disease 2019 in high-risk outpatients using real-world data and relevant references.</p></div><div><h3>Methods</h3><p>In the decision-tree model, 2 cohorts were organized in a single center to compare the cost-effectiveness between the Azvudine plus symptomatic treatment group and the symptomatic treatment group. We calculated the cost and mortality rate for both groups. The incremental cost-effectiveness ratio was used to illustrate the cost-effectiveness. To assess the uncertainty of the model parameters, we conducted 1-way and probabilistic sensitivity analyses.</p></div><div><h3>Findings</h3><p>In total, there were 804 outpatients included in the model. Among these, 317 patients received Azvudine plus symptomatic treatment, whereas the remaining 487 participants were treated with symptomatic treatment alone. The costs in the Azvudine and control groups were 1055.48 yuan and 2466.97 yuan and the survival rates were 100.00% and 98.70%, respectively. After calculation, the incremental cost-effectiveness ratio was determined to be −108,817.48 yuan per person. In the section of 1-way and probabilistic sensitivity analyses, Azvudine was still proven to be cost-effective.</p></div><div><h3>Implications</h3><p>Our results support the usage of Azvudine for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 from economic perspective.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999557","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":"Cost-effectiveness Analysis of COMT-inhibitors as Adjuvant Treatments to Levodopa in Patients with Advanced Parkinson's Disease","authors":"Nayoung Kwak MS ,&nbsp;Myung-Jun Lee MD ,&nbsp;Hye-Young Kang PhD ,&nbsp;Hankil Lee PhD","doi":"10.1016/j.clinthera.2024.06.016","DOIUrl":"10.1016/j.clinthera.2024.06.016","url":null,"abstract":"<div><h3>Purpose</h3><p>We aimed to elicit scientific evidence on the cost-effectiveness of two catechol-O-methyltransferase inhibitors (COMT-i) versus no COMT-i in patients with advanced Parkinson's disease.</p></div><div><h3>Methods</h3><p>A mixed model of the decision tree and a Markov model with three health states by OFF-time level (&lt;25%, ≥25%, and death) was constructed to compare opicapone (OPC), entacapone (ENT), and no COMT-i over a lifetime. A hypothetical cohort of 10,000 patients was created and simulated based on the characteristics of the BIPARK trial subjects.</p></div><div><h3>Findings</h3><p>Two COMT-i (OPC and ENT) were identified as a cost-effective option compared to no COMT-i. Probabilistic sensitivity analysis showed that over 90% of the simulations proved the robust cost-effectiveness of COMT-i. When the time horizon as the most influential factor decreases to a 5- and 10-year period, COMT-i can be a cost-saving option. Although ENT may be the preferred option over OPC economically because of its lower price, OPC can be acceptable if the drug price is reduced by 17%.</p></div><div><h3>Implications</h3><p>Add-on treatment with COMT-i in patients with PD receiving levodopa/carbidopa appears to be cost-saving compared with not using COMT-i. In the future, it is necessary to evaluate the economic evaluation of COMT-i based on long-term real-world evidence.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874372","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":"HARMONIZE Asia: A Phase III Randomized Study to Investigate the Efficacy and Safety of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China","authors":"Xinling Liang MD, PhD ,&nbsp;Wanhong Lu MD, PhD ,&nbsp;Xueqing Yu MD, PhD ,&nbsp;Hong Cheng MD ,&nbsp;Qiang He MD ,&nbsp;Qingfeng Peng MD ,&nbsp;Zhaohui Ni MD, PhD ,&nbsp;Gang Long MD, PhD ,&nbsp;Lihua Wang MD, PhD ,&nbsp;Wei Chen MD, PhD ,&nbsp;Rong Li MD ,&nbsp;June Zhao MD, PhD ,&nbsp;Yong Zhang PhD ,&nbsp;Vera Lisovskaja PhD ,&nbsp;Zhiji Tang MSc, PhD","doi":"10.1016/j.clinthera.2024.07.004","DOIUrl":"10.1016/j.clinthera.2024.07.004","url":null,"abstract":"<div><h3>Purpose</h3><p>Sodium zirconium cyclosilicate (SZC) is an oral potassium (K⁺)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia.</p></div><div><h3>Methods</h3><p>This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K⁺ (sK⁺) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK⁺ 3.5–5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK⁺ during RTP Days 8 to 29. Secondary endpoints included mean change in sK⁺ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia.</p></div><div><h3>Findings</h3><p>In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK⁺ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; <em>P</em> &lt; 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK⁺ versus placebo in a dose-dependent manner (each <em>P</em> &lt; 0.001); least-squares means (95% confidence interval [CI]) sK⁺ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; <em>P</em> = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; <em>P</em> &lt; 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each <em>P</em> &lt; 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation.</p></div><div><h3>Implications</h3><p>Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK⁺ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.</p></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901192","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}