Clinical therapeutics最新文献

{"title":"The Influence of Invasive Candida Infections on Prognosis and Analysis of Their Risk Factors After Liver Transplantation.","authors":"Chunjiao Long, Weiting Peng, Jie Zhao, Qiquan Wan","doi":"10.1016/j.clinthera.2024.09.012","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.012","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the incidence, timing, risk factors, and impacts of invasive Candida infections (ICIs) within 3 months after liver transplantation (LT) on LT recipients' prognosis.</p><p><strong>Methods: </strong>Patients undergoing LT from January 2015 to December 2022 in a tertiary university hospital were investigated the incidence, onset, and risk factors of ICIs and the effects of ICIs on the outcome of LT recipients using statistical methods.</p><p><strong>Findings: </strong>The mean age of involved 389 LT recipients was 47.3 ± 10.5 years, with 322 (82.8%) being men. The incidence of ICIs was 3.3% (13/389), and the median time between LT and onset of ICIs was 5.0 days. The univariate analysis of predictors of ICIs identified that massive blood loss, prolonged duration of central line and urethral catheter, and prophylactic antifungal therapy were related to post-LT ICI risk. Multivariate logistic regression analysis adjusted for men and age identified that intraoperative blood loss ≥5000 mL (odds ratio [OR] = 7.005, 95% CI: 2.084-23.542, P = 0.002) and central line duration >14 days (OR = 5.270, 95% CI: 1.556-17.854, P = 0.008) were independently associated with the development of post-LT ICIs. Post-LT prophylactic antifungal therapy >3 days reduced ICIs (OR = 0.103, 95% CI: 0.021-0.501, P = 0.005). Regarding clinical outcomes, patients with ICIs were more likely to stay in the intensive care unit for 7 days or longer compared with those without ICIs (OR = 6.910, 95% CI: 1.737-27.493, P = 0.006). ICIs had no impact on hospitalization stay and 1-month all-cause mortality after LT.</p><p><strong>Implications: </strong>ICIs are frequent and occur early after LT. Predictors of post-LT ICIs were massive intraoperative blood loss and prolonged duration of the central line. However, post-LT prophylactic antifungal therapy reduced ICIs. Patients with ICIs stayed longer in the intensive care unit than those without ICIs.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379233","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":"Drug Review and Approval Policies Based on Real-world Evidence in China and the United States: A Comparative Study.","authors":"Munire Mohetaer, Adili Tuersun, Pei Li, Su Wang, Xingyan Zhang, Yuwen Chen","doi":"10.1016/j.clinthera.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.009","url":null,"abstract":"<p><strong>Purpose: </strong>The use of real-world evidence (RWE) in regulatory reviews and approvals is currently experiencing significant changes amid increasingly active discussions, primarily reflected in relevant policies, regulations, and guidance documents. However, disparities persist between China and the United States regarding the acceptance and formulation of policies for incorporating real-world data/evidence (RWD/E) in regulatory evaluation and authorization. Furthermore, the current policies lack specific operational details necessary for effective implementation and widespread adoption.</p><p><strong>Methods: </strong>After conducting a systematic literature review and comparing relevant policies, regulations, and guidelines, as well as the related information published on their official websites, we analyze key aspects of RWE-based drug review and approval policies to highlight similarities and differences in these policies between China and the United States.</p><p><strong>Findings: </strong>This paper reviews the frameworks and existing guidelines in China and the U.S., discussing similarities and differences observed in key policy aspects, including relevant definitions, data sources, data standards, data quality, and connectivity, information requirements, study design, personnel training, and communication, including an example of the application of RWE in drug review and approval processes.</p><p><strong>Implications: </strong>Further develop and refine RWE policies, encourage cooperation, and share best practices and successful examples to enhance the effectiveness of policy implementation and increase its social acceptance.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379231","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":"Population Pharmacokinetic Model of Intravenous Immunoglobulin in Patients Treated for Various Immune System Disorders.","authors":"Jian Lynn Lee, Noraida Mohamed Shah, Mohd Makmor-Bakry, Farida Islahudin, Hamidah Alias, Shamin Mohd Saffian","doi":"10.1016/j.clinthera.2024.09.018","DOIUrl":"10.1016/j.clinthera.2024.09.018","url":null,"abstract":"<p><strong>Purpose: </strong>Intravenous immunoglobulin (IVIG) is used to treat various immune system disorders, but the factors influencing its disposition are not well understood. This study aimed to estimate the population pharmacokinetic parameters of IVIG and to investigate the effect of genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor (FcRn) and clinical variability on the pharmacokinetic properties of IVIG in patients with immune system disorders.</p><p><strong>Methods: </strong>Patients were recruited from 4 hospitals in Malaysia. Clinical data were recorded, and blood samples were taken for pharmacokinetic and genetic studies. Population pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling in Monolix. Age, weight, baseline immunoglobulin G concentration, ethnicity, sex, genotype, disease type, and comorbidity were investigated as potential covariates. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive checks, and bootstrap analysis.</p><p><strong>Findings: </strong>A total of 292 blood samples were analyzed from 79 patients. The IVIG concentrations were best described by a 2-compartment model with linear elimination. Weight was found to be an important covariate for volume of distribution in the central compartment (Vc), volume of distribution in the peripheral compartment (Vp), and clearance in the central compartment, whereas disease type was found to be an important covariate for Vp. Goodness-of-fit plots indicated that the model fit the data adequately. Genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor did not affect the pharmacokinetic properties of IVIG.</p><p><strong>Implications: </strong>This study supports the use of dosage based on weight as per current practice. The study findings highlight that Vp is significantly influenced by the type of disease being treated with IVIG. This relationship suggests that different disease types, particularly inflammatory and autoimmune conditions, may alter tissue permeability and fluid distribution due to varying degrees of inflammation. Increased inflammation can lead to enhanced permeability and retention of IVIG in peripheral tissues, reflecting higher Vp values.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Upadacitinib in Children with Severe Atopic Dermatitis","authors":"Yuli Qian PhD ,&nbsp;Eliza M. Raymundo MD ,&nbsp;Shuai Hao PhD ,&nbsp;Kristina Unnebrink PhD ,&nbsp;Gweneth F. Levy MD ,&nbsp;Henrique D. Teixeira PhD ,&nbsp;Alvina D. Chu MD ,&nbsp;Zachary A. Zinn MD ,&nbsp;Amy S. Paller MD ,&nbsp;Wei Liu PhD ,&nbsp;Mohamed-Eslam F. Mohamed RPh, PhD, FCP","doi":"10.1016/j.clinthera.2024.07.003","DOIUrl":"10.1016/j.clinthera.2024.07.003","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to characterize the pharmacokinetics, safety, tolerability, and exploratory efficacy of upadacitinib, an oral Janus kinase inhibitor approved for treating moderate to severe atopic dermatitis (AD) in adults and adolescents, in children with severe AD.</div></div><div><h3>Methods</h3><div>In an open-label, multiple-dose, Phase 1 study, pediatric patients with severe AD from two age groups (2 to &lt;6 years and 6 to &lt;12 years) received bodyweight-based dosing regimens of upadacitinib using either twice-daily immediate-release (IR) oral solution or once-daily extended-release (ER) tablets. A pharmacokinetic assessment was conducted on Day 7 of the study, which was followed by a long-term safety and exploratory efficacy evaluation for up to 108 weeks. The results reported here are based on an interim analysis when the study had completed enrollment and pharmacokinetic assessment.</div></div><div><h3>Findings</h3><div>A total of 35 patients were enrolled and received upadacitinib. The maximum upadacitinib plasma concentration was attained within a median time of 0.5 to 2 hours and 2 to 2.5 hours for the IR oral solution and ER tablet formulations, respectively. Upadacitinib functional half-life was generally shorter with IR oral solution relative to ER tablets. Upadacitinib apparent oral clearance decreased with decreasing body weight in the pediatric patients enrolled in this study. Upadacitinib was generally safe and well tolerated. The most common (≥3 patients) adverse events were upper respiratory tract infection, COVID-19 infection, headache, abdominal discomfort, vomiting, asthma, and cough. No new safety risks were identified compared to the known safety profile for upadacitinib in adults and adolescents. In the 30 patients with available exploratory efficacy data at Week 12, 36.7% achieved validated Investigator's Global Assessment scale for AD score of 0 or 1 (Validated Investigator Global Assessment for AD 0/1), and 70.0% had Eczema Area and Severity Index (EASI) improvement of at least 75% (EASI 75).</div></div><div><h3>Implications</h3><div>The characterized pharmacokinetic profiles in this study, together with the observed safety and exploratory efficacy results, support further investigation of the current upadacitinib dosing regimen in future confirmatory Phase 3 clinical trials in children with AD.</div><div>Clinical Trial Number: NCT03646604, registered 2018-08-23</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981913","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":"Safety and Tolerability of Anti–microRNA-328 Ophthalmic Solution, SHJ002, in Pediatric Subjects: First-in-Human Clinical Study","authors":"Jiunn-Liang Chen MD ,&nbsp;Wei-Yu Lai MD ,&nbsp;Reuy-Tay Lin MD ,&nbsp;Suh-Hang H. Juo MD, PhD ,&nbsp;Chung-Ling Liang MD, PhD","doi":"10.1016/j.clinthera.2024.08.015","DOIUrl":"10.1016/j.clinthera.2024.08.015","url":null,"abstract":"<div><h3>Purpose</h3><div>microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children.</div></div><div><h3>Methods</h3><div>This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability.</div></div><div><h3>Findings</h3><div>There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as “unrelated to study drug.”</div></div><div><h3>Implications</h3><div>SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials. ClinicalTrials.gov identifier: NCT04928144.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145353","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":"Pediatric Drug Development: Lessons Learned to Shape the Future of Drug Development Strategies for Our Little Patients","authors":"Yuli Qian PhD","doi":"10.1016/j.clinthera.2024.09.017","DOIUrl":"10.1016/j.clinthera.2024.09.017","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Aflibercept and Ranibizumab in the Treatment of Retinopathy of Prematurity","authors":"Tiantian Yang MSc,&nbsp;Jing Zhang MD,&nbsp;Qingfei Hao MD,&nbsp;Shouhui Ma MBBS,&nbsp;Xiuyong Cheng MD","doi":"10.1016/j.clinthera.2024.08.011","DOIUrl":"10.1016/j.clinthera.2024.08.011","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare the efficacy, recurrence rate, and recurrence interval of intravitreal injection of aflibercept (IVA) and ranibizumab (IVR) in patients with retinopathy of prematurity (ROP).</div></div><div><h3>Methods</h3><div>This is a single-center retrospective study of neonates hospitalized from January 2018 to March 2023 in the Department of Neonatology of the First Affiliated Hospital of Zhengzhou University who received intravitreal injection of anti-vascular endothelial growth factor owing to type 1 prethreshold ROP, threshold ROP, or aggressive posterior ROP. Clinical data were collected to record the cure, recurrence, number of injections, and side effects of ROP.</div></div><div><h3>Findings</h3><div>A total of 224 neonates (444 eyes) were enrolled in this study, of which 121 (241 eyes) received IVA and 103 (203 eyes) received IVR. There were no significant differences in the general characteristics of infants between the two groups (<em>P</em> &gt; 0.05). The corrected gestational age of the first injection was 37.27 ± 3.07 weeks in the IVA group and 37.20 ± 4.89 weeks in the IVR group (<em>P</em> = 0.582). The recurrence rate was 15.8% in the IVA group and 14.9% in the IVR group (<em>P</em> = 0.841). For relapsed infants, the postmenstrual age (PMA) was 34.89 ± 3.49 weeks in the IVA group and 35.28 ± 4.43 weeks in the IVR group at the first treatment. The PMA was 43.69 ± 4.57 and 40.96 ± 4.98 weeks at the second treatment in the IVA and IVR groups, respectively (<em>P</em> = 0.185). There were two children in the IVA group that required a third treatment, with PMAs of 58.71 and 57.29 weeks at the time of surgery, and one child in the IVR group, with a PMA of 43.14 weeks at the time of injection (<em>P</em> = 0.221). No complications were recorded in either group.</div></div><div><h3>Implications</h3><div>The efficacies of aflibercept and ranibizumab in treating ROP are similar, and the safety of the medications was good. Further research should be conducted in large-scale, prospective clinical trials, providing ophthalmologists with new options for the treatment of ROP.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379232","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":"Venetoclax Clinical Pharmacokinetics After Administration of Crushed, Ground or Whole Tablets","authors":"","doi":"10.1016/j.clinthera.2024.03.012","DOIUrl":"10.1016/j.clinthera.2024.03.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Venetoclax is a potent, orally bioavailable BCL-2 inhibitor used in the treatment of some hematological malignancies. Crushing tablets may be necessary to help with the administration of venetoclax to patients with swallowing difficulties or patients requiring nasogastric tube feeding. The study was conducted to assess the bioavailability of crushed and finely ground venetoclax tablets relative to whole tablets.</div></div><div><h3>Methods</h3><div>An open-label, randomized, 3-way, crossover study in 15 healthy adult females was conducted. Venetoclax tablets were administered orally in a crushed, ground or intact form on Day 1 of each period with water following a high-fat breakfast. Pharmacokinetic samples were collected up to 72 hours postdosing.</div></div><div><h3>Findings</h3><div>The crushed and ground tablets met the bioequivalence criteria (0.80–1.25) relative to the intact tablets with respect to area under the concentration-time curve to time of the last measurable concentration (AUC_t) and to infinite time (AUC_inf) but exhibited a slightly lower maximum plasma concentration (C_max). This was not considered clinically significant as only venetoclax overall exposure (AUC) has been shown to correlate with clinical efficacy. There was no change in the physical appearance and the evaluated physicochemical properties of crushed and ground venetoclax tablets after 72 hours of storage at 25°C/60% relative humidity.</div></div><div><h3>Implications</h3><div>Crushing or grinding venetoclax tablets before administration could be considered as a viable alternative method of administration for patients who have difficulty swallowing whole venetoclax tablets or patients requiring nasogastric tube feeding.</div></div><div><h3>ClinicalTrials.gov identifiers</h3><div>NCT05909553, registered June 12, 2023.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086989","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":"Weight Loss With Once-nightly Sodium Oxybate for the Treatment of Narcolepsy: Analysis From the Phase III Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) Trial","authors":"Thomas Roth PhD ,&nbsp;Anne Marie Morse DO ,&nbsp;Richard Bogan MD ,&nbsp;Asim Roy MD ,&nbsp;Jennifer Gudeman PharmD ,&nbsp;Yves Dauvilliers MD, PhD","doi":"10.1016/j.clinthera.2024.07.010","DOIUrl":"10.1016/j.clinthera.2024.07.010","url":null,"abstract":"<div><h3>Purpose</h3><div>Individuals with narcolepsy are more likely to be obese than the general population. Changes in weight-related measures with extended-release, once-nightly sodium oxybate (ON-SXB) and characteristics of participants with ≥5% weight loss were assessed in a Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) trial post hoc analysis.</div></div><div><h3>Methods</h3><div>REST-ON (NCT02720744) was a Phase III, double-blind, placebo-controlled, multicenter, randomized clinical trial. Participants aged ≥16 years with narcolepsy type 1 (NT1) or NT2 received ON-SXB or placebo for 13 weeks (week 1, 4.5 g; weeks 2–3, 6 g; weeks 4–8, 7.5 g; and weeks 9–13, 9 g). Weight and body mass index were measured at baseline and study end.</div></div><div><h3>Findings</h3><div>Weights were similar between groups at baseline (mean [SD]; ON-SXB, 81.2 [20.8] kg; N = 107 [NT1, n = 80; NT2, n = 27]; placebo, 82.1 [22.5] kg; N = 105 [NT1, n = 82; NT2, n = 23]). At week 13 (9 g), mean (SD) weight decreased 1.3 (3.6) kg with ON-SXB and increased 0.2 (2.6) kg with placebo; 17.8% (19/107; NT1, n = 14; NT2, n = 5) of participants receiving ON-SXB had ≥5% weight loss versus 3.8% receiving placebo (4/105; NT1, n = 3; NT2, n = 1; <em>P</em> = 0.001). At week 13, least squares mean (SE) body mass index change from baseline was ‒0.51 (0.13) kg/m² with ON-SXB and 0.08 (0.13) kg/m² with placebo (least squares mean difference [95% CI], −0.59 [−0.95 to −0.23] kg/m²; <em>P</em> = 0.001). Excessive daytime sleepiness improved for both groups with ON-SXB, the ≥5% weight-loss subgroup exhibited larger improvement in the Maintenance of Wakefulness Test and Epworth Sleepiness Scale versus the other subgroup (weight loss &lt;5%, no change, or weight gain) (Maintenance of Wakefulness Test, <em>P</em> = 0.019; Epworth Sleepiness Scale score, <em>P</em> &lt; 0.001).</div></div><div><h3>Implications</h3><div>Narcolepsy is often associated with obesity, which may increase cardiometabolic risks. ON-SXB, an effective treatment for excessive daytime sleepiness and cataplexy, may be preferred in overweight or obese individuals to provide a more tailored treatment approach.</div></div><div><h3>ClinicalTrials.gov identifier</h3><div>NCT02720744.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995477","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":"Effect of Raloxifene Treatment on Apolipoproteins and Lipoprotein(a) Concentrations in Postmenopausal Women: A Meta-Analysis of Randomized Controlled Trials","authors":"Xinyi Liao ,&nbsp;Jian Deng ,&nbsp;Lei Du ,&nbsp;Benjamin Hernández-Wolters ,&nbsp;Kousalya Prabahar ,&nbsp;Hamed Kord-Varkaneh","doi":"10.1016/j.clinthera.2024.07.008","DOIUrl":"10.1016/j.clinthera.2024.07.008","url":null,"abstract":"<div><h3>Background and Aim</h3><div>Although various randomized controlled trials (RCTs) have evaluated the effect of raloxifene on apolipoproteins and lipoprotein(a) concentrations in postmenopausal women, the results have been inconsistent and inconclusive. Therefore, we conducted this meta-analysis of RCTs to investigate the effect of raloxifene administration on apolipoproteins and lipoprotein(a) [Lp(a)] concentrations in postmenopausal women.</div></div><div><h3>Methods</h3><div>Two independent researchers systematically searched the scientific literature (including PubMed/Medline, Scopus, Web of Science, and EMBASE) for English-language randomized controlled trials (RCTs) published up to June 2024. We included RCTs reporting the impact of raloxifene on apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and Lp(a) levels in postmenopausal women. The primary outcome of interest was change in Lp(a), and the secondary outcomes were changes in ApoA-I and ApoB.</div></div><div><h3>Findings</h3><div>The present meta-analysis incorporated 12 publications with 14 RCT arms. The comprehensive outcomes derived from the random-effects model revealed a statistically significant increase in ApoA-I (WMD: 6.06 mg/dL, 95% CI: 4.38, 7.75, <em>P</em> &lt; 0.001) and decrease in ApoB concentrations (WMD: -8.48 mg/dL, 95% CI: -10.60, -6.36, <em>P</em> &lt; 0.001) and Lp(a) (WMD: -3.02 mg/dL, 95% CI: -4.83, -1.21, <em>P</em> &lt; 0.001) following the administration of raloxifene in postmenopausal women. In the subgroup analyses, the increase in ApoA-I and the decrease in ApoB and Lp(a) levels were greater in RCTs with a mean participant age of ≥60 years and a duration of ≤12 weeks.</div></div><div><h3>Implications</h3><div>The current meta-analysis of RCTs demonstrates that treatment with raloxifene reduces ApoB and Lp(a) levels while increasing ApoA-I levels in postmenopausal women. Since these effects on lipid components are associated with a reduced risk of cardiovascular disease (CVD), raloxifene could be a suitable therapy for postmenopausal women who are at an increased risk of CVD and have other medical indications for raloxifene administration.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055163","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}