Advances in Therapy最新文献

{"title":"A Randomized Phase I Trial Evaluating Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eclitasertib, a RIPK1 Inhibitor, in Healthy Participants.","authors":"Christine Farenc, Pierre-Francois Clot, Salvatore Badalamenti, Annie J Kruger, Robert J Pomponio, Tillmann Krahnke, Heribert Staudinger, Yong Lin","doi":"10.1007/s12325-025-03255-y","DOIUrl":"https://doi.org/10.1007/s12325-025-03255-y","url":null,"abstract":"<p><strong>Introduction: </strong>Receptor-interacting protein kinase 1 (RIPK1) is a master regulator of inflammation and necroptotic cell death and is implicated in the pathogenesis of several inflammatory and neurodegenerative diseases. This first-in-human study assessed the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of eclitasertib, a selective, peripherally-restricted, oral inhibitor of RIPK1.</p><p><strong>Methods: </strong>This 2-part Phase I trial enrolled healthy participants aged 18-55 years. Part 1 consisted of 2 sub-parts. Part 1a was a double-blind, randomized, single ascending dose (SAD) study with 6 cohorts of 8 participants each randomized 3:1 to single oral dose of eclitasertib (10 mg, 30 mg, 100 mg, 200 mg, 400 mg, or 800 mg) or placebo. Part 1b was an open-label, randomized, three-sequence, cross-over design study to evaluate the relative bioavailability of the prototype formulation versus the drug substance and the effect of food in an independent cohort of 10 participants. Part 2 was a double-blind, randomized, multiple ascending dose study (MAD) with 4 cohorts of 10 participants each randomized 4:1 to receive eclitasertib (50 mg, 100 mg, 200 mg, or 600 mg once daily) or placebo orally for 14 days. Incidence of adverse events (AEs; primary outcome), PK (secondary outcome), and PD properties (exploratory outcome; assessed by reduction in levels of S166 phosphorylated RIPK1) were evaluated.</p><p><strong>Results: </strong>Single and multiple oral doses of eclitasertib were well tolerated, with no study drug-related severe or serious AEs reported. Medical device-site reactions (includes AEs classified as device-site reaction, vessel puncture-site hematoma/pain, catheter-site pain/hematoma and catheter-site-related reactions) and headache were the most commonly reported AEs in both parts. Overall, the median T_max ranged from 3 to 4 h. C_max and AUC increased sub-dose proportionally. Administration of eclitasertib 100 mg following a high-fat meal did not significantly impact its bioavailability. At doses of 100 mg and above, > 90% inhibition of RIPK1 phosphorylation in human peripheral blood mononuclear cells was observed with eclitasertib at 12 h post-dose in both SAD and MAD studies.</p><p><strong>Conclusions: </strong>Single and repeated doses of eclitasertib were well tolerated in healthy participants and potently inhibited RIPK1 activation.</p><p><strong>Trial registration: </strong>EudraCT 2019-001350-25.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324157","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":"Obesity and Schizophrenia: Results of a Feasibility Study with Semaglutide to Assist Weight Loss.","authors":"Adrian H Heald, Gavin Reynolds, Isabel Nash, Onagh Boyle, Chris Daly, Damien Longson, Donal O'Shea, Joseph Ingram, Richard Holt, Joseph Firth, Mike Stedman, Akheel Syed, Marc de Hert","doi":"10.1007/s12325-025-03261-0","DOIUrl":"https://doi.org/10.1007/s12325-025-03261-0","url":null,"abstract":"<p><strong>Introduction: </strong>Weight gain has come to define the life experience of many individuals with schizophrenia and other severe enduring mental illnesses (SMI). In this clinical intervention study, we aimed to determine whether weekly treatment with the glucagon-like peptide-1 (GLP-1) agonist, semaglutide, as part of usual care, is feasible and acceptable to individuals in a psychiatric inpatient setting.</p><p><strong>Methods: </strong>Fifteen inpatients (11 men/4 women) in a secure care environment, diagnosed with schizophrenia or schizoaffective disorder and with body mass index (BMI) of at least 30 kg/m² were commenced on weekly subcutaneous semaglutide as per standard of care. BMI and glycated haemoglobin (HbA1c) were measured at baseline and monthly follow-up to 6 months, and quality of life (QOL) was surveyed at baseline and 6 months. Analysis was based on intention-to-treat.</p><p><strong>Results: </strong>Mean age of patients was 37 years (range 23-63). Time since diagnosis varied from 2 to 25 years. Mean initial BMI was 48.7 kg/m² for women and 37.2 kg/m² for men. Duration of semaglutide treatment ranged from 2-6 months. EuroQol 5-Dimensional Questionnaire, 5-Level Version Visual Analogue Scale (EQ5D5L QOL VAS) showed a mean improvement of + 7.5 (from 60 to 67.5) points. Improvement in QOL was overall significantly greater in those who remained on semaglutide (+ 9.5) than those who discontinued. Six patients discontinued semaglutide before the study end, including two who were discharged and no longer able to receive the intervention, and four who withdrew due to medical concerns. Individual percentage weight change varied from + 1 to - 12% (median 5%), and weight reduction was seen in all except two patients. All but one patient demonstrated a reduction in HbA1c levels. Mean HbA1c fell significantly from 41 (range 34-47) mmol/mol to 35.3 (31-45) mmol/mol. Importantly, all patients with baseline HbA1c in the non-diabetic hyperglycaemia range (42-47 mmol/mol) demonstrated a reduction of HbA1c to below 42 mmol/mol by 3 months. Prior to initiation of semaglutide, mean blood pressure was 127 (range 117-145) mmHg systolic and 82 (62-99) mmHg diastolic. At last assessment, average blood pressure was reduced to 121 (107-136) mmHg systolic and 79 (65-96) mmHg diastolic.</p><p><strong>Conclusion: </strong>In this feasibility study, weekly semaglutide treatment was associated with improvement in self-rated overall QOL and reductions in BMI, HbA1c and blood pressure at up to 6 months follow-up. Even in patients who discontinued treatment before 6 months, initial benefits of weight reduction and improved QOL were still demonstrated. Further evaluation, including health economic assessment and longer-term follow up, may support the expanded use of GLP-1 agonists in improving the cardiometabolic profile and longitudinal health outcomes in individuals with SMI.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324160","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":"Renin-Angiotensin-Aldosterone System Inhibitor Dosing After Initiation of Outpatient Sodium Zirconium Cyclosilicate Therapy: The GALVANIZE RAASi Real-World Evidence Study.","authors":"Abiy Agiro, Ali Greatsinger, Fan Mu, Erin E Cook, Jingyi Chen, Manasvi Sundar, Angela Zhao, Ellen Colman, Arun Malhotra","doi":"10.1007/s12325-025-03254-z","DOIUrl":"https://doi.org/10.1007/s12325-025-03254-z","url":null,"abstract":"<p><strong>Introduction: </strong>The use of renin-angiotensin-aldosterone system inhibitors (RAASi), including mineralocorticoid receptor antagonists (MRAs), can cause or exacerbate hyperkalemia, especially in patients with chronic kidney disease (CKD) and heart failure (HF). Prior research has demonstrated that sodium zirconium cyclosilicate (SZC) can enable continued RAASi use in patients with hyperkalemia. This study, GALVANIZE RAASi, sought to describe the proportion of patients with hyperkalemia who had an optimized or maximized RAASi dose after the initiation of outpatient SZC therapy.</p><p><strong>Methods: </strong>Using data from a large US insurance claims database from July 2018-December 2022, adults initiating SZC in the outpatient setting (index) while using a RAASi (≥ 7 day overlap with index and ≥ 1 RAASi fill in the 6-month follow-up period) were selected. Sub-studies included patients with baseline diagnosis codes for CKD or HF and patients with ≥ 1 MRA prescription during follow-up. The proportion of patients with an optimized (≥ 50% of target dose) or maximized (≥ 100% of target dose) RAASi dose during follow-up was described.</p><p><strong>Results: </strong>Of the 2973 patients meeting study inclusion criteria who were included in the overall sample, 2549 were included in the CKD sub-study, 879 in the HF sub-study and 395 in the MRA sub-study. In the overall sample, 63.7% of patients had an optimized RAASi dose and 27.2% of patients had a maximized RAASi dose during follow-up, and the results were similar across sub-studies (optimized RAASi dose: 62.9-72.6%; maximized RAASi dose: 26.9-36.1%).</p><p><strong>Conclusion: </strong>In this real-world study of patients with RAASi use after SZC initiation, about two-thirds of patients had an optimized RAASi dose and more than a quarter of patients had a maximized RAASi dose within 6 months of starting SZC. Findings were consistent across sub-studies of patients with CKD, HF and treatment with MRA. SZC may support the maintenance of optimal RAASi therapy; however, further comparative analyses are warranted. Graphical abstract available for this article.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324161","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":"Modelled Weight Loss in an English Population Eligible for Bariatric Surgery: A Retrospective Open Cohort Study.","authors":"Dimitri J Pournaras, João Diogo da Rocha Fernandes, Sara Holloway, Alistair Marsland, Abd A Tahrani, Silvia Capucci","doi":"10.1007/s12325-025-03267-8","DOIUrl":"https://doi.org/10.1007/s12325-025-03267-8","url":null,"abstract":"<p><strong>Introduction: </strong>In this study, we aimed to quantify the economic consequences of limited access to obesity treatment and estimate the effect of modelled weight loss in a population who were eligible for bariatric surgery.</p><p><strong>Methods: </strong>This was a retrospective open cohort study using data from the Discover database (1 January 2010-31 December 2019). Index was the first day that individuals were aged ≥ 18 years and eligible for bariatric surgery [body mass index (BMI) ≥ 40.0 kg/m² (obesity class III), or 35.0-39.9 kg/m² (obesity class II) and an obesity-related complication]. Time to surgery, healthcare costs and the impact of modelled weight loss over 2 years on estimated healthcare costs were assessed.</p><p><strong>Results: </strong>In total, 137,184 individuals were eligible for bariatric surgery, of whom 3241 (2.4%) ultimately received surgery during follow-up. Individuals who received surgery were slightly younger, and were more likely to be women and white, than the population eligible for surgery. Overall, 36.6% of individuals underwent surgery ≥ 4 years after they became eligible. Mean annual per-person healthcare costs increased 75% between year 1 and year 8 of the period before surgery in this group [from 1150 British pound sterling (GBP) to 2013 GBP]. Modelled weight loss of 10% would result in 58.3% of eligible individuals transitioning to obesity class I after 2 years, with only 12.2% remaining in obesity class III, resulting in a 14.3% reduction in healthcare costs. Greater degrees of weight loss were associated with greater estimated reductions in BMI and cost.</p><p><strong>Conclusion: </strong>Delays to prompt weight management support appear to be associated with increasing healthcare costs, which could be mitigated by improving access to weight management.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324159","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":"Risk of Cardiovascular Events, Infections, and Renal Complications in Postsurgical Chronic Hypoparathyroidism: A US Medicare Claims Retrospective Analysis.","authors":"Wahidullah Noori, Christopher T Sibley, Viktor V Chirikov, Kyle Roney, Alden R Smith","doi":"10.1007/s12325-025-03264-x","DOIUrl":"https://doi.org/10.1007/s12325-025-03264-x","url":null,"abstract":"<p><strong>Introduction: </strong>Hypoparathyroidism (HypoPT) is an endocrine disease caused by insufficient levels of parathyroid hormone and is associated with impaired health-related quality of life. This study assessed the clinical burden among individuals with postsurgical chronic HypoPT in Medicare Fee-For-Service.</p><p><strong>Methods: </strong>Adults (aged ≥ 18 years) with newly diagnosed HypoPT (N = 1166) were identified from the Medicare 100% Limited Data Set between July 1, 2017, and March 31, 2020. All had a confirmed diagnosis within 6-12 months after index diagnosis and were required to be continuously enrolled for ≥ 6 months pre index and ≥ 12 months post index. A random sample of non-HypoPT controls (N = 11,258) was synthetically assigned an index date of diagnosis to ensure similar baseline and follow-up periods as individuals with postsurgical chronic HypoPT. The two cohorts were compared before and after matching with respect to the risk of cardiovascular (CV) events, renal complications, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and mortality.</p><p><strong>Results: </strong>Individuals with postsurgical chronic HypoPT were older than non-HypoPT controls (mean age 69 vs. 64 years), more were female (76% vs. 57%), had higher Charlson Comorbidity Index scores (3.24 vs. 0.73), and a higher prevalence of moderate-to-severe renal disease (28.8% vs. 5.6%), nephrocalcinosis (59.9% vs. 0.6%), and nephrolithiasis (8.3% vs. 1.0%). They also had significantly greater mortality (hazard ratio [HR]  2.75). The incident risks of composite CV events (HR 1.35), renal complications (HR 4.92), UTIs (HR 2.09), and URTIs (HR 1.46) were greater in subcohorts without those conditions prior to index. After matching for baseline characteristics, the elevated risk of renal complications, UTIs, and URTIs remained while there was no difference in the risk of CV events or death between individuals with postsurgical chronic HypoPT and controls.</p><p><strong>Conclusion: </strong>The substantial clinical burden of postsurgical chronic HypoPT in Medicare patients highlights the treatment gaps associated with current therapy and the need for parathyroid hormone replacement therapies.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324162","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":"Economic Burden of Postsurgical Chronic Hypoparathyroidism: A US Medicare Claims Retrospective Analysis.","authors":"Wahidullah Noori, Christopher T Sibley, Viktor V Chirikov, Kyle Roney, Alden R Smith","doi":"10.1007/s12325-025-03265-w","DOIUrl":"https://doi.org/10.1007/s12325-025-03265-w","url":null,"abstract":"<p><strong>Introduction: </strong>Approximately 75% of hypoparathyroidism (HypoPT) cases result from removal of or injury to parathyroid glands during anterior neck surgery. HypoPT persisting 6 months following surgery carries a significant economic burden. This study aims to describe the economic burden of postsurgical chronic HypoPT in the Medicare population.</p><p><strong>Methods: </strong>Data from the Medicare 100% Limited Data Set between July 1, 2017, and March 31, 2020, were utilized to identify newly diagnosed adults with a confirmed HypoPT diagnosis (n = 1,166) after surgery (index) and their healthcare resource utilization (HCRU) and costs compared with those of control patients who were non-HypoPT (n = 11,258). Continuous enrollment for ≥ 6 months pre- and ≥ 12 months post-index was required. Individuals with postsurgical chronic HypoPT were matched 1:2 to controls on age, gender, race, region, Charlson Comorbidity Index score, and index year. Three economic burden definitions for HCRU and costs were evaluated in unmatched and matched groups: all-cause, direct HypoPT, and HypoPT plus related long-term complications.</p><p><strong>Results: </strong>Compared with matched controls (n = 1,107), individuals with postsurgical chronic HypoPT (n = 607) had significant differences in baseline number of hospitalizations (0.53 vs. 0.14), outpatient visits (11.40 vs. 1.51), and total medical costs (US$160,899 vs. $21,288). Over a median of 31 months of follow-up, mean all-cause total medical costs per patient per year (PPPY) were significantly higher among individuals with postsurgical chronic HypoPT ($227,036 vs. $109,306; P < 0.001), largely attributable to higher all-cause medical utilization among the postsurgical chronic HypoPT group (0.72 vs. 0.37 hospitalizations PPPY; 14.4 vs. 7.44 outpatient visits PPPY). Multivariable regression analysis showed that all-cause cost burden among patients with postsurgical chronic HypoPT was 1.57-3.00 times higher, depending on adjustment for baseline renal comorbidities, compared with controls.</p><p><strong>Conclusion: </strong>The economic burden of postsurgical chronic HypoPT in patients who use Medicare is substantial, highlighting the need for innovative treatments to improve outcomes and quality of life.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324158","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":"Patient Preferences for Treatment Attributes in Inflammatory Bowel Disease: A Discrete Choice Experiment Among Patients in Five Non-Western Countries.","authors":"Marjorie Argollo, Yoon K An, Nahla Azzam, Domingo C Balderramo, Olga Fadeeva, Chia-Jung Kuo, Julie Laurent, Elenore Uy","doi":"10.1007/s12325-025-03249-w","DOIUrl":"https://doi.org/10.1007/s12325-025-03249-w","url":null,"abstract":"<p><strong>Introduction: </strong>Understanding patient preferences is important for facilitating informed decision-making in managing patients with inflammatory bowel disease (IBD). This study explored the preferences of patients with Crohn's disease (CD) and ulcerative colitis (UC) regarding advanced therapy treatment attributes in five non-Western countries: Argentina, Australia, Brazil, Saudi Arabia and Taiwan.</p><p><strong>Methods: </strong>Adult patients with self-reported CD or UC treated for ≥ 6 months participated in this cross-sectional online survey. A discrete choice experiment assessed the relative importance of treatment attributes using conditional logit models. The primary objective was to estimate partworth utilities across the five countries (overall population).</p><p><strong>Results: </strong>Overall, 706 patients with CD and UC (n = 353 each) completed the survey (mean age 36.8 and 37.7 years; female 47.9% and 47.6%; mean disease duration 4.5 and 4.6 years, respectively). For patients with CD, the rate of long-term remission on maintenance therapy (LTREM) was the most preferred treatment attribute (32.5%), followed by the rate of 1-year remission (25.7%), routes of administration (RoAs; 24.6%) and risk of serious adverse events (AEs) (11.5%) and mild AEs (5.8%). For patients with UC, the rate of corticosteroid-free remission after 1 year was the most important attribute (30.8%), followed by RoAs (27.4%), rate of mucosal healing after 1 year (16.1%), LTREM (14.9%) and risk of serious AEs (10.0%) and mild AEs (0.8%). Patients in both groups considered abdominal pain as the symptom most impacting their quality of life. Approximately half of the patients (CD 49.3%; UC 50.5%) exposed to advanced therapy indicated that they would have preferred to start advanced therapy earlier.</p><p><strong>Conclusion: </strong>Patients with IBD from non-Western countries prioritised advanced treatment attributes such as efficacy outcomes and RoAs, although treatment preferences varied between patients with CD and UC. Shared decision-making between patients and physicians regarding advanced therapy choice and timing should occur throughout the treatment journey.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315760","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":"Long-Term Mortality and Morbidity Impact on Patients with Pulmonary Arterial Hypertension (PAH) If Access to Sotatercept Is Delayed: A Simulation Model.","authors":"Adnan Alsumali, Vallerie McLaughlin, Jestinah Chevure, Rogier Klok, Wenjie Zhang, Eliana C Martinez, Christine Pausch, Janethe De Oliveira Pena, Gijs van de Wetering, Murvin Jootun, Dominik Lautsch, Marius M Hoeper","doi":"10.1007/s12325-025-03241-4","DOIUrl":"https://doi.org/10.1007/s12325-025-03241-4","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT, where BGT included mono-, double-, or triple-PAH targeted therapy. Building on the trial's findings, a population health model was recently published assessing the long-term clinical impact of sotatercept. This analysis expands on this model and compares the clinical outcomes of immediate treatment initiation with sotatercept plus BGT against delayed treatment initiation with sotatercept plus BGT using a six-state Markov-type model and over a lifetime horizon.</p><p><strong>Methods: </strong>State-transition probabilities were obtained from STELLAR, while mortality rates adjusted for risk strata and probabilities of lung/heart-lung transplants were derived from COMPERA PAH registry data and literature.</p><p><strong>Results: </strong>In the base case, a 2-year delay in treatment with sotatercept plus BGT resulted in an average of 12.4 years life expectancy, whereas immediate initiation of sotatercept led to an average of 16.5 years, a difference of 4.1 years. Immediate treatment with sotatercept plus BGT was also associated with a gain in infused prostacyclin-free life-years and resulted in 210 PAH hospitalizations avoided and 5 lung/heart-lung transplant avoided per 1000 patients.</p><p><strong>Conclusions: </strong>This research suggests that early addition of sotatercept to BGT has the potential to increase life expectancy among patients with PAH and to reduce PAH hospitalizations, prostacyclin-use, and lung/heart-lung transplants needs. Real-world data are needed to confirm these findings, guiding clinicians and healthcare decision-makers in optimizing PAH treatment strategies.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT04576988 (STELLAR).</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315759","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":"Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer.","authors":"Mehmet A Bilen, Sabree Burbage, Carmine Rossi, Ibrahim Khilfeh, Lilian Diaz, Yuxi Wang, Dominic Pilon, Gordon Brown, Neal Shore, Benjamin Lowentritt, Daniel W Lin","doi":"10.1007/s12325-025-03270-z","DOIUrl":"https://doi.org/10.1007/s12325-025-03270-z","url":null,"abstract":"<p><strong>Introduction: </strong>This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous recombination repair-negative (HRR-) metastatic castration-sensitive prostate cancer (mCSPC).</p><p><strong>Methods: </strong>Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017-12/31/2022). Outcomes were compared between patients with ≥ 1 positive BRCA test (BRCA+) and those without detected HRR mutations (HRR-) using weighted Kaplan-Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.</p><p><strong>Results: </strong>In total, 149 patients with BRCA+ and 1066 with HRR- mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR) = 1.45 (95% confidence interval (CI) 1.10, 1.92), p = 0.009]; median TTNT was shorter in the BRCA+ than the HRR- cohort (10.9 vs. 18.7 months). By 24 months, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to castration resistance [72.2% vs. 61.4%; HR = 1.46 (95% CI 1.16, 1.84), p = 0.001]; median TTCR was shorter in the BRCA+ than HRR- cohort (12.9 vs. 16.9 months). Numerically fewer patients in the BRCA+ than the HRR- cohort survived 24 months after PC diagnosis [80.6% vs. 85.4%; HR = 1.46 (95% CI 0.99, 2.14), p = 0.054].</p><p><strong>Conclusion: </strong>Findings demonstrate worse outcomes for patients with BRCA+ mCSPC treated with available advanced therapies, supporting the need for effective genetically targeted therapies in this population.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315758","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":"Systematic Review of the Use of the WHO-5 Well-Being Index Across Different Disease Areas.","authors":"Arnau Domenech, Ismail Kasujee, Volker Koscielny, Christopher E M Griffiths","doi":"10.1007/s12325-025-03266-9","DOIUrl":"https://doi.org/10.1007/s12325-025-03266-9","url":null,"abstract":"<p><strong>Background: </strong>Since its first publication in 1998, the 5-item World Health Organization Well-being index, WHO-5, has become one of the most widely used questionnaires to assess subjective psychological well-being.</p><p><strong>Aims: </strong>To perform a systematic review of the WHO-5 questionnaire, with a focus on its use across various disease areas and patient populations.</p><p><strong>Methods: </strong>Studies reporting the use of the WHO-5 were searched on the PubMed and PsycINFO databases (search December 2024). The classification of the different diseases or disorders was used following the 11th version of the International Classification of Diseases.</p><p><strong>Results: </strong>A total of 552 studies met the predefined criteria for inclusion in the review. We provide an overview of the WHO-5 use in all different disease areas, the psychological burden of the patients, and if available, the impact of the treatments on their well-being. The groups with the most publications refer to the Coronavirus disease (COVID)-19 pandemic (n = 161, 29.2%) followed by the group of mental, behavioral, or neurodevelopmental disorders (n = 141, 25.6%), and the group of endocrine, nutritional, and metabolic diseases (n = 120, 21.7%).</p><p><strong>Conclusions: </strong>The WHO-5 is a short questionnaire consisting of 5 positively formulated questions, which successfully detect when a disease impacts a person's subjective well-being. The scale proved to detect changes in well-being across various diseases around the world, and it should be considered in clinical practice and research.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281958","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}