Advances in Therapy最新文献

{"title":"A Review of the Utilization of Relative Dose Intensity and Dose Delay Factor in Health Technology Appraisals of Oncology Drugs in Solid Tumors.","authors":"Anandaroop Dasgupta, Ankita Kaushik, Shubhram Pandey, Sumeet Attri, Paul Miller, Keith Tolley","doi":"10.1007/s12325-025-03358-6","DOIUrl":"https://doi.org/10.1007/s12325-025-03358-6","url":null,"abstract":"<p><strong>Introduction: </strong>Relative dose intensity (RDI) and dose delay factor (DDF) are important variables in cost-effectiveness analyses of oncology drugs that impact incremental cost-effectiveness ratios (ICERs). However, there is little published evidence on how RDI and DDF affect ICERs and how the calculation and application of these measures vary across health technology appraisals (HTAs). To understand this further, we analyzed National Institute for Health and Care Excellence (NICE) HTAs.</p><p><strong>Methods: </strong>The NICE website was manually searched for HTAs (submissions, Evidence Review Group appraisals, and company responses) of treatments in solid tumors from date of inception to March 31, 2024. Data were extracted on RDI/DDF calculation methods, application in economic models, HTA body feedback, and impact on ICERs.</p><p><strong>Results: </strong>Of 265 HTAs sourced, 63 were identified for further review based on inclusion of RDI/DDF variables. Seven HTAs for solid tumors and 12 breast cancer HTAs were analyzed; breast cancer was chosen as a model as it is a leading cause of cancer mortality. RDI ranged from 85% to 100% across all HTAs. Approaches to calculating and applying RDI varied widely in these models, with some distinguishing between dose reductions, delays, and missed doses, while others used a single RDI metric. For combination therapies, RDI was sometimes applied differently across components. The NICE appraisal committees frequently raised concerns about lack of transparency in RDI calculations and assumptions around delayed/missed doses and wastage. Excluding RDI adjustments generally increased ICERs by 5%-10%.</p><p><strong>Conclusions: </strong>There is heterogeneity in how RDI and dose modifications are handled in UK oncology HTAs. Areas for improvement that can support more informed HTA decision making include developing standardized methods for handling RDI/DDF that better reflect clinical practice, providing clearer regulatory guidance, conducting real-world dose-intensity studies, improving data collection, and creating tools to consistently incorporate dose data into economic models.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991096","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":"Real-World Outcomes with Orelabrutinib in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Retrospective Study.","authors":"Zi Wang, Congwei Jia, Xuan Wang, Yan Zhang, Daobin Zhou, Wei Zhang","doi":"10.1007/s12325-025-03344-y","DOIUrl":"10.1007/s12325-025-03344-y","url":null,"abstract":"<p><strong>Introduction: </strong>Orelabrutinib is a novel Bruton's tyrosine kinase inhibitor with high selectivity and a favorable safety profile. Despite substantial benefits in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with orelabrutinib, real-world data remain scarce. This study aimed to evaluate the efficacy and safety of orelabrutinib regimens for CLL/SLL in a real-world setting.</p><p><strong>Methods: </strong>Between June 1, 2018, and September 30, 2024, a total of 63 patients with CLL/SLL who received an orelabrutinib-based regimen were included in this retrospective study. Data on demographics and characteristics, treatment, outcomes, and safety were retrospectively collected and analyzed. Outcomes included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Of the 63 included patients, 18 (28.6%) patients received orelabrutinib-based regimen as first-line therapy, 33 (52.4%) as second-line therapy, and 12 (19.0%) as third-line therapy. The ORR and DCR were 90.5% (57/63, 95% CI 80.4-96.4) and 96.8% (61/63, 95% CI: 89.0-99.6), respectively. Regarding different treatment lines, ORR was 94.4% (17/18) for first-line therapy, 93.9% (31/33) for second-line therapy, and 75.0% (9/12) for third-line therapy. At a median follow-up of 72.0 months (range: 24.0-216.0), the median PFS and OS were not reached. The 36-month PFS rate was 80.7% (95% CI 61.4-100.0) and the 36-month OS rate was 85.5% (95% CI 67.4-100.0). Thirty-eight (60.3%) patients experienced at least one adverse event (AE) of any grade during orelabrutinib therapy, with no treatment-related deaths observed. Among the 31 patients previously treated with ibrutinib/zanubrutinib, AEs reported during prior therapy mostly resolved or improved in severity after switching to orelabrutinib.</p><p><strong>Conclusion: </strong>Orelabrutinib was effective and well tolerated for patients with CLL/SLL, providing evidence of clinical benefit in real-world settings.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938795","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":"Pharmacokinetic Bridging Between an Autoinjector and a Prefilled Syringe Following Subcutaneous Administration of Mirikizumab in Healthy Participants.","authors":"Xin Zhang, Yuki Otani, Christopher D Payne, Nathan J Morris, Laiyi Chua, Rodrigo Escobar, Sihe Wang, Galen Shi","doi":"10.1007/s12325-025-03335-z","DOIUrl":"10.1007/s12325-025-03335-z","url":null,"abstract":"<p><strong>Introduction: </strong>Mirikizumab, a humanized anti-interleukin-23p19 monoclonal antibody, is approved for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). Two phase 1, open-label, two-arm, randomized studies compared pharmacokinetics and safety of mirikizumab (200 mg, Study AMBW; 300 mg, Study AMBX) to establish bioequivalence. Mirikizumab was administered subcutaneously using an autoinjector or a prefilled syringe (PFS) as a single dose in healthy participants.</p><p><strong>Methods: </strong>Participants (male and female) were randomized 1:1 to mirikizumab by a PFS (reference) and an autoinjector (test). Participants were sub-randomized (1:1:1) to one of three injection sites (abdomen, arm, thigh) and stratified into one of three weight groups. Primary endpoints were maximum observed drug concentration (C_max), and area under concentration versus time curves (time zero to infinity [AUC_0-∞]; time to last time point with measurable concentration [AUC_0-tlast]). Secondary objectives were safety and immunogenicity.</p><p><strong>Results: </strong>In Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for C_max, AUC_0-∞, and AUC_0-tlast were within prespecified bioequivalence limits (0.80-1.25). Similar results were observed in Study AMBX, after administration of mirikizumab 300 mg, with bioequivalence achieved for AUC_0-tlast and AUC_0-∞, while the upper bound of the 90% CI of the geometric least squares mean ratio for C_max was slightly above the bioequivalence upper threshold. Overall safety of mirikizumab was similar between devices in both studies. Immunogenicity was similar overall in Study AMBW, but slightly higher (autoinjector versus PFS) in Study AMBX.</p><p><strong>Conclusion: </strong>Mirikizumab administered by autoinjector or PFS was considered bioequivalent at the 200-mg UC maintenance dose and the 300-mg CD maintenance dose. Safety and immunogenicity profiles were comparable between autoinjector and PFS. Availability of an autoinjector option may be preferred by some patients and may help improve patient adherence to treatment.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov NCT04607733; NCT05069896.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938793","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":"Emerging Concepts in Diagnosis, Pathologic Features, and Treatment of Limbic-Predominant Amnestic Neurodegenerative Syndrome (LANS): A Narrative Review.","authors":"Macie A Serio, Drew R Dethloff, Grant C Curry, Maya L Beesley, Sahar Shekoohi, Alan D Kaye","doi":"10.1007/s12325-025-03337-x","DOIUrl":"https://doi.org/10.1007/s12325-025-03337-x","url":null,"abstract":"<p><strong>Introduction: </strong>Neurodegenerative disorders (NDs) are characterized by progressive loss of function and destruction of the central and peripheral nervous systems. These disorders result in devastating irreversible cognitive decline and affect millions of people worldwide. Alzheimer's disease (AD) is a common cause of dementia that increases in incidence with increasing age. Limbic-predominant amnestic neurodegenerative syndrome (LANS) is another common etiology of amnestic symptoms and often affects the \"oldest-old\" of the population. The two disorders share many similarities yet are clearly pathologically distinct. Establishing robust classifications to distinguish these two disorders is key to future management and care of an aging population. The present investigation explored the pathophysiology of neurodegenerative disorders (NDs), specifically Alzheimer's disease (AD), limbic-predominant amnestic neurodegenerative syndrome (LANS), and limbic-predominant age-related TDP-43 encephalopathy (LATE).</p><p><strong>Methods: </strong>We performed a comprehensive narrative review of the literature, covering studies from database inception through November 2024. We searched PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and Google Scholar for relevant publications. We also reviewed reference lists of key articles. Two authors independently screened titles/abstracts for relevance and extracted data on study design, patient population, neuropathologic findings, imaging/biomarker methods, and clinical features. Discrepancies were resolved by discussion. This review synthesized findings on the need for LANS criteria and compared LANS to AD and LATE across clinical, imaging, pathologic, and biomarker domains.</p><p><strong>Results: </strong>A comprehensive analysis of the key pathologic features and distinctions among selected neurodegenerative syndromes was carried out using peer-reviewed literature.</p><p><strong>Conclusions: </strong>Recently proposed clinical criteria for LANS are a milestone in the characterization and further treatment of neurodegenerative disease. Understanding the minute differences in pathophysiology among various NDs allows for pioneering more targeted disease-modifying treatments. This narrative review provides concise reflection between AD and other NDs involving LATE-NC changes.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938785","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":"Effectiveness of Mepolizumab in Patients with OCS-Dependent Severe Asthma: A Real-World Study.","authors":"Sevim Bavbek, Mona Al-Ahmad, Hala Samaha, Pooran Chand Kathuria, Patricia Fernandez, Nasser Al Busaidi, Tayseer Ibrahim, Bassam Mahboub, Seema Haider, Saeed Noibi, Gur Levy, Riyad Omar Al-Lehebi","doi":"10.1007/s12325-025-03338-w","DOIUrl":"https://doi.org/10.1007/s12325-025-03338-w","url":null,"abstract":"<p><strong>Introduction: </strong>Before the availability of biologic therapies, the main treatment for patients with severe asthma in Asia, Latin America, and the Middle East was oral corticosteroids (OCS), despite long-term use causing serious adverse effects. This post hoc analysis of the NUCALA Effectiveness Study (NEST) evaluated the effectiveness of mepolizumab, an anti-interleukin-5 monoclonal antibody, in patients with severe asthma and OCS dependence from regions with limited representation in real-world studies.</p><p><strong>Methods: </strong>NEST was a multicountry, observational cohort study in adults with severe asthma from Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Patients received ≥ 1 dose of 100 mg mepolizumab. OCS dependence was defined as receiving maintenance OCS at mepolizumab initiation or for ≥ 26 weeks during the 12 months prior. Data were collected 12 months pre- and post-initiation. Outcomes included OCS use, rate of clinically significant exacerbations (CSEs), and level of asthma symptom control.</p><p><strong>Results: </strong>Of 524 patients with OCS use data, 58.4% (n = 306) had OCS dependence pre-initiation. Mean (standard deviation) age was 49.2 (13.4) years; 73.9% (n = 226) were women. Of 251 patients with available data, 87.6% (n = 220) received lower OCS doses post-initiation and 68.9% (n = 173) stopped OCS use altogether. CSEs were reduced by 76.9% post-initiation. Of 222 patients with available data, 72.5% (n = 161) had improvements in Asthma Control Test scores post-initiation.</p><p><strong>Conclusion: </strong>In patients with severe asthma and OCS dependence from the countries studied, mepolizumab reduced OCS use and dose, asthma exacerbations, and improved symptom control.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938838","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 and Physician Preferences for Maintenance Treatment in Advanced Non-Small Cell Lung Cancer: Insights into Treatment Selection.","authors":"Manasee V Shah, Caitlyn T Solem, Anne Liao, Kelly F Bell, Yao Wang, Hongbo Yang, Yan Meng, Mingchen Ye, Umit Tapan","doi":"10.1007/s12325-025-03347-9","DOIUrl":"https://doi.org/10.1007/s12325-025-03347-9","url":null,"abstract":"<p><strong>Introduction: </strong>Advanced/metastatic non-small cell lung cancer (a/mNSCLC) is associated with a poor prognosis. Although maintenance therapy after first-line (1L) induction treatment can extend survival, it may also present with drawbacks like risk of certain adverse events (AEs), underscoring the need for shared decision-making between patients and their treating physicians. This study aimed to quantify the extent to which maintenance treatment attributes impact the preferences of patients and physicians after 1L induction therapy for a/mNSCLC.</p><p><strong>Methods: </strong>Eligible patients (aged ≥ 18 years in the UK and US) were diagnosed with a/mNSCLC and had stable disease with or responded to 1L induction therapy. Eligible physicians were licensed oncologists with ≥ 5 years' experience in a/mNSCLC treatment who had treated ≥ 20 such patients in the past year. Surveys assessed the patients' and physicians' perspectives regarding the current treatment landscape of a/mNSCLC, and a discrete choice experiment assessed their preferences regarding treatment characteristics. Data were collected using choice cards, designed to capture treatment attribute preferences including efficacy (progression-free survival [PFS] and overall survival [OS]), chance (risk) of new brain metastasis (BM), and selected AEs.</p><p><strong>Results: </strong>Among 34 UK and 48 US patients, the three most important treatment attributes (in order) were chance of new BM, OS, and risk of severe neutropenia. Among 51 UK and 50 US treating physicians, the 3 most important treatment attributes (in order) were OS, chance of new BM, and PFS.</p><p><strong>Conclusion: </strong>In this real-world survey, OS and chance of new BM were the two most important maintenance treatment attributes for patients with a/mNSCLC and treating physicians. However, the risk of severe neutropenia carried greater relative importance, while PFS carried lesser relative importance, for patients than physicians. These results highlight the differing emphasis placed on attributes by patients and physicians when selecting maintenance treatment.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938846","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":"Real-World Weight Loss Observed With Semaglutide and Tirzepatide in Patients with Overweight or Obesity and Without Type 2 Diabetes (SHAPE).","authors":"Carmen D Ng, Victoria Divino, Julia Wang, Joshua C Toliver, Marcio Buss","doi":"10.1007/s12325-025-03340-2","DOIUrl":"https://doi.org/10.1007/s12325-025-03340-2","url":null,"abstract":"<p><strong>Introduction: </strong>Semaglutide 2.4 mg injection (Wegovy^®), a glucagon-like peptide-1 (GLP-1) receptor agonist, was approved by the US Food and Drug Administration for weight management in June 2021. Tirzepatide, a glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, was approved for type 2 diabetes mellitus (T2DM; Mounjaro^®) in May 2022 and weight management (Zepbound^®) in November 2023. Due to limited data on the long-term effectiveness of these medications, this study assessed real-world weight loss with semaglutide 2.4 mg or tirzepatide after 1 year in patients with overweight or obesity and without T2DM.</p><p><strong>Methods: </strong>This retrospective cohort study included adults with overweight or obesity and ≥ 1 pharmacy claim for semaglutide 2.4 mg or tirzepatide in the US Komodo Health database between June 4, 2021, and December 15, 2023. Patients had continuous enrollment for 1 year before (baseline period) and 1 year after (follow-up period) the index date (date of treatment initiation) and persistence on therapy (no gap of > 30 days' supply) during follow-up. Patients with T2DM at baseline were excluded. Weight change from index to 1 year was descriptively assessed.</p><p><strong>Results: </strong>Overall, 9916 patients were included (semaglutide 2.4 mg, n = 6794; tirzepatide, n = 3122). Baseline characteristics were descriptively similar for semaglutide 2.4 mg and tirzepatide: mean age was 47.8 and 49.5 years, 79.8% and 77.9% were female, and mean index weight was 104.5 and 104.9 kg, respectively. After 1 year of follow-up, the mean weight loss from baseline with semaglutide 2.4 mg and tirzepatide was - 14.6 and - 17.2 kg, respectively, with percent weight loss of - 14.1% and - 16.5%. Most (83.5%) patients treated with semaglutide 2.4 mg reached the maximum dose (2.4 mg), while 25.9% of patients treated with tirzepatide reached the maximum dose (15 mg).</p><p><strong>Conclusion: </strong>Findings suggest semaglutide 2.4 mg and tirzepatide are used in descriptively similar populations and both resulted in clinically meaningful weight loss after 1 year of treatment.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938848","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 Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease","authors":"Gerd R. Burmester,&nbsp;Atul Deodhar,&nbsp;Alan D. Irvine,&nbsp;Remo Panaccione,&nbsp;Kevin L. Winthrop,&nbsp;Ruth Ann Vleugels,&nbsp;Gweneth Levy,&nbsp;Smitha Suravaram,&nbsp;Hannah Palac,&nbsp;Lani Wegrzyn,&nbsp;Sharanya Ford,&nbsp;Sebastian Meerwein,&nbsp;Emma Guttman-Yassky","doi":"10.1007/s12325-025-03328-y","DOIUrl":"10.1007/s12325-025-03328-y","url":null,"abstract":"<div><h3>Introduction</h3><p>We report the long-term safety of upadacitinib (oral, selective, and reversible Janus kinase inhibitor) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), atopic dermatitis (AD), Crohn’s disease (CD), and ulcerative colitis (UC).</p><h3>Methods</h3><p>Data were analyzed from 16 studies (data cutoff August 15, 2024). Each treatment group was pooled across studies within each indication. Active comparator arms included adalimumab (RA/PsA) and methotrexate (RA). Treatment-emergent adverse events (TEAEs) were reported as exposure-adjusted incidence rates per 100 patient-years (<i>n</i>/100 PY).</p><h3>Results</h3><p>This analysis included 8632 (RA, <i>n</i> = 3209; PsA, <i>n</i> = 907; AS, <i>n</i> = 596; nr-axSpA, <i>n</i> = 286; AD, <i>n</i> = 2683; CD, <i>n</i> = 450; UC, <i>n</i> = 501) upadacitinib-treated patients over 27,164.2 patient-years (range 199.4–12,315.8 PY across indications). Rates (<i>n</i>/100 PY) of any TEAEs ranged from 112.0 (AS) to 401.1 (RA). Most frequently reported TEAEs included COVID-19, upper respiratory tract infection, nasopharyngitis, herpes zoster, urinary tract infection, and acne (primarily patients with AD). Serious TEAEs ranged from 4.5 (AD) to 11.0 (UC), and those leading to discontinuation ranged from 2.9 (AS) to 8.3 (UC). TEAEs leading to death ranged from 0 (nr-axSpA, UC) to 0.7 (RA). Among upadacitinib-treated patients across indications, rates of adverse events of special interest ranged from 1.3 to 4.6 (serious infection), 2.4–6.6 (herpes zoster), 0.2–0.9 (malignancy excluding nonmelanoma skin cancer [NMSC]), 0–1.4 (NMSC), 0–0.5 (major adverse cardiovascular event [MACE]), 0–0.9 (venous thromboembolism [VTE]), and 0–9.2 (elevated creatine kinase). In RA and PsA, herpes zoster, NMSC, and elevated creatine kinase rates were numerically higher with upadacitinib vs active comparators. Serious infection, herpes zoster, malignancy (excluding NMSC), NMSC, MACE, and VTE rates remained stable over time.</p><h3>Conclusion</h3><p>This descriptive analysis indicates a long-term safety profile of upadacitinib consistent with previous reports, further supporting long-term treatment of chronic diseases with upadacitinib. Variations in TEAE rates across indications likely reflected differences in populations and underlying comorbidities.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov identifiers NCT02675426, NCT02706951, NCT02706847, NCT02629159, NCT02706873, NCT03086343, NCT03104374, NCT03104400, NCT03178487, NCT04169373, NCT03569293, NCT03568318, NCT03607422, NCT03345823, NCT02819635.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"5215 - 5237"},"PeriodicalIF":4.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03328-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938804","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":"A New Ashwagandha Formulation (Zenroot™) Alleviates Stress and Anxiety Symptoms While Improving Mood and Sleep Quality: A Randomized, Double-Blind, Placebo-Controlled Clinical Study","authors":"Manasvi Mahadevan,&nbsp;Kumarpillai Gopukumar,&nbsp;Ruchi Gupta,&nbsp;Abhijeet Morde,&nbsp;Paras Patni,&nbsp;Sahitya Sarvamangala Srinivas,&nbsp;Arun Bhuvanendran,&nbsp;Abhijith Phanindra","doi":"10.1007/s12325-025-03327-z","DOIUrl":"10.1007/s12325-025-03327-z","url":null,"abstract":"<div><h3>Introduction</h3><p>Prolonged exposure to stress may lead to low mood, anxiety, depression, insomnia, and metabolic disorders. Ashwagandha, an established adaptogen, is known to combat stress. We studied the safety and efficacy of Ashwagandha formulation, Zenroot™ (ZEN), containing 1.5% total withanolides on stress, anxiety, mood, and sleep quality in human subjects with non-chronic mild to moderate stress.</p><h3>Methods</h3><p>This was a prospective, randomized, double-blind, parallel, placebo-controlled, clinical interventional study with supplementation duration of 84 days. Ninety subjects were randomly assigned in a 1:1 ratio to receive 125 mg of ZEN or placebo. We measured stress using the Perceived Stress Scale (PSS) score as a primary endpoint. Various secondary endpoints included Mindfield eSense Skin Response (SCR) and Mindfield eSense PULSE Heart Rate Variability (HRV)–Root Mean Square of Successive Differences (RMSSD), and standard deviation of normal NN interval (SDNN), Beck Anxiety Inventory (BAI), Profile of Mood States (POMS), Pittsburgh Sleep Quality Index (PSQI), stress biomarkers of serum cortisol, and salivary alpha amylase (sAA) levels and safety parameters. The study assessments were performed on days 0, 14, 28, 56, and 84.</p><h3>Results</h3><p>All 90 randomized subjects completed the study. Mean ± standard error (SE) age of subjects in the ZEN group was 35.5 ± 1.3 years and in the placebo group was 34.5 ± 1.2 years. ZEN 125 mg showed significant (<i>p</i> &lt; 0.05) improvements in PSS, BAI, and PSQI scores on days 28, 56, and 84; SCR on days 14, 28, and 84 and trend (<i>p</i> &lt; 0.1) on day 56; HRV-RMSSD and SDNN on day 14; and POMS on days 56 and 84. No significant differences were observed between the two groups for serum cortisol and sAA. The study product was well tolerated without any safety concerns.</p><h3>Conclusion</h3><p>We observed significant reductions in both subjective and objective measures of stress with improvement in mood, sleep quality, and occasional anxiety symptoms. ZEN was well tolerated without any related adverse events. Future clinical studies are warranted to evaluate the effect of ZEN on chronically stressed adults.</p><p>Clinical Trial Registration Number: http://ctri.nic.in/Identifier:CTRI/2024/03/063786.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"5238 - 5254"},"PeriodicalIF":4.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03327-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938822","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 Evaluation and Budget Impact Analysis of Indocyanine Green Test for Preoperative Liver Function in Patients with Major Hepatectomy in Thailand","authors":"Unchalee Permsuwan,&nbsp;Pajaree Sriuttha,&nbsp;Chutwichai Tovikkai,&nbsp;Anon Chotirosniramit,&nbsp;Asara Thepbunchonchai,&nbsp;Sunhawit Junrungsee,&nbsp;Worakitti Lapisatepun,&nbsp;Kittipong Chaiyabutr,&nbsp;Tharatip Srisuk,&nbsp;Piyameth Dilokthornsakul","doi":"10.1007/s12325-025-03341-1","DOIUrl":"10.1007/s12325-025-03341-1","url":null,"abstract":"<div><h3>Introduction</h3><p>Post-hepatectomy liver failure (PHLF) remains a significant cause of morbidity and mortality following liver resections. Indocyanine green (ICG) clearance testing provides quantitative liver function assessment to improve perioperative risk stratification. However, its cost poses a concern in resource-limited settings like Thailand. This study aimed to evaluate the cost-utility and budget impact of adding ICG testing to standard diagnosis compared to standard diagnosis alone in patients undergoing first major hepatectomy.</p><h3>Methods</h3><p>A hybrid model combining a decision tree and Markov model was developed from a societal perspective over a lifetime horizon. Clinical data and cancer treatment costs were derived from 400 real-world patients admitted to four university hospitals. PHLF costs were sourced from the National Health Security Office and utility values were directly collected from patients admitted for major hepatectomy. Primary outcomes included total costs, life years, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied. A variety of sensitivity analyses were conducted to test parameter uncertainty. A 5-year budget impact analysis was also performed from a payer’s perspective, calculating the net budget impact (NBI) between both strategies.</p><h3>Results</h3><p>Compared to standard diagnosis alone, adding ICG testing increased costs by 3600 Thai baht (THB) [102 US dollars ($)] and gained 0.001 QALYs, yielding an ICER of 2,763,973 THB/QALY ($78,321). The probability of cost-effectiveness at the ceiling threshold of 160,000 THB/QALY ($4,534) was 6.3%. The ICER would fall below this threshold if PHLF risk exceeded 10.1% or if ICG test cost decreased by at least 88%. The 5-year NBI was 39.5 million THB ($1.1 million), reduced by 47.3% with dose-sharing.</p><h3>Conclusion</h3><p>Although not cost-effective at current thresholds, ICG reduces PHLF-related costs and maintains an acceptable NBI per year.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"5202 - 5214"},"PeriodicalIF":4.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03341-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938820","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}