Advances in Therapy最新文献

{"title":"Real-World Prophylaxis Outcomes with rIX-FP and rFIXFc for Males with Hemophilia B: Pooled Analysis of Medical Chart Data from Germany and Italy","authors":"Johannes Oldenburg,&nbsp;Martin Olivieri,&nbsp;Songkai Yan,&nbsp;Ying Yang,&nbsp;Radovan Tomic,&nbsp;Xiang Zhang,&nbsp;Douglass Drelich,&nbsp;Natalie Jakobs,&nbsp;Mariasanta Napolitano","doi":"10.1007/s12325-025-03303-7","DOIUrl":"10.1007/s12325-025-03303-7","url":null,"abstract":"<div><h3>Introduction</h3><p>The current standard of care for people with severe hemophilia B is prophylaxis with factor IX (FIX) products. This analysis assessed the effectiveness of prophylaxis for people with hemophilia B (PwHB) receiving rIX-FP or rFIXFc prophylaxis in Germany and Italy. </p><h3>Methods</h3><p>A retrospective, de-identified chart review included PwHB ≥ 12 years with severe/moderate hemophilia B from Germany or Italy, receiving prophylaxis with rIX-FP or rFIXFc for ≥ 12 months. The primary outcome was FIX consumption; the secondary outcomes were dosing interval, annualized bleeding rate (ABR), annualized spontaneous bleeding rate (AsBR), and annualized joint bleeding rate (AjBR). These outcomes were also explored in PwHB with pre- and post-rIX-FP switch data.</p><h3>Results</h3><p>Of 194 PwHB, 107 and 87 received rIX-FP and rFIXFc prophylaxis, respectively. The mean FIX consumption of rIX-FP was significantly lower compared to rFIXFc (42.4 vs. 65.2 IU/kg/week, <i>p</i> = 0.0001), with mean dosing intervals of 9.5 days (rIX-FP) and 7.9 days (rFIXFc). The mean bleeding rates for rIX-FP versus rFIXFc, respectively, were: ABR 0.7 versus 1.1 (<i>p</i> = 0.6704), AsBR 0.1 versus 0.3 (<i>p</i> = 0.3427), and AjBR 0.3 versus 0.4 (<i>p</i> = 0.5296). Subgroup analyses for PwHB with severe and moderate hemophilia B separately showed similar numerical patterns when comparing these outcomes. In the 18 patients with switch data, a significant reduction in FIX consumption was observed (median 51.7 to 33.3 IU/kg/week, <i>p</i> = 0.0069), and the mean dosing interval was extended (7.2–9.5 days). The ABR (median 1.6–0.0, <i>p</i> = 0.0172; <i>n</i> = 18) and AjBR (median 0.6–0.0, <i>p</i> = 0.0200; <i>n</i> = 14) decreased significantly, while the AsBR decreased but not significantly (median 0.2–0.0, <i>p</i> = 0.1460; <i>n</i> = 14).</p><h3>Conclusion</h3><p>rIX-FP prophylaxis was associated with reduced FIX consumption versus rFIXFc and offered equally effective or potentially improved bleed protection. Additionally, PwHB who switched to rIX-FP achieved significant decreases in FIX consumption, ABR, and AjBR compared with their prior FIX product.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4583 - 4596"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03303-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688595","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":"Evaluating the Compositional Quality of Probiotics Containing Bacillus clausii in India","authors":"Dhanasekhar Kesavelu,&nbsp;Sridhar Ganpathy,&nbsp;Pramod Jog,&nbsp;Bhaswati Acharya,&nbsp;Vivek Saxena,&nbsp;Nivedita Telang,&nbsp;Nilesh Gaikwad","doi":"10.1007/s12325-025-03289-2","DOIUrl":"10.1007/s12325-025-03289-2","url":null,"abstract":"<div><h3>Introduction</h3><p>The quality of probiotics is crucial for their effectiveness and safety. Many studies have found discrepancies between the claimed and the actual content of microorganisms in probiotics. However, only few studies have assessed the quality of these products in India. This study aimed to evaluate the quality of various probiotics containing <i>Bacillus clausii</i> in India.</p><h3>Methods</h3><p>Eleven commercially available probiotics containing <i>Bacillus clausii</i> were selected: Enterogermina® (reference product), Bifilac clausii™, Entromax®, Progermina™, Entroflora™, Novogermina™, Tufpro™, Gutgermina®, Eco-All™, Entero clausi™, and Medogermina®. Suspensions were cultured and subcultured in selective media to identify <i>Bacillus clausii</i> colonies. Purity, viable spore load, and antibiotic resistance were assessed.</p><h3>Results</h3><p>The assessed parameters varied significantly among the probiotics. Enterogermina® was contamination-free, with a spore count of 2 billion/5 mL and showed resistance to all tested antibiotics. Progermina™ and Eco-all™ had higher spore counts than claimed but were contaminated with <i>Bacillus cereus</i>. Contaminants were found in all products except Enterogermina® and Medogermina®. Most of the products showed no antibiotic resistance.</p><h3>Conclusion</h3><p>The study revealed significant differences in the quality of probiotics on the Indian market, highlighting concerns about their potency and safety. Stringent quality control is necessary to ensure consumer safety and help healthcare professionals make informed decisions.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4571 - 4582"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03289-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688592","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":"Correction to: Effectiveness and Safety of Tezepelumab in a Diverse Population of US Patients with Severe Asthma: Initial Results of the PASSAGE Study","authors":"Njira L. Lugogo,&nbsp;Praveen Akuthota,&nbsp;Kaharu Sumino,&nbsp;Sameer K. Mathur,&nbsp;Autumn F. Burnette,&nbsp;Andrew W. Lindsley,&nbsp;Jean-Pierre Llanos,&nbsp;Claudio Marchese,&nbsp;Christopher S. Ambrose,&nbsp;Benjamin Emmanuel","doi":"10.1007/s12325-025-03316-2","DOIUrl":"10.1007/s12325-025-03316-2","url":null,"abstract":"","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4724 - 4725"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03316-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688591","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":"Obstructive Sleep Apnea: An Evolving Therapeutic Landscape with an Emerging Role for Incretin-Based Therapies","authors":"Bolong Xu,&nbsp;Kaveh Gaynor-Sodeifi,&nbsp;Vaishnavi Kundel","doi":"10.1007/s12325-025-03312-6","DOIUrl":"10.1007/s12325-025-03312-6","url":null,"abstract":"<div><p>Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by repetitive collapse of the upper airway during sleep, resulting in intermittent hypoxemia and sleep fragmentation. OSA is a highly prevalent condition, strongly associated with obesity and linked to an increased risk of cardiovascular disease. While traditional therapies such as positive airway pressure (PAP) devices are effective in treating OSA and alleviating daytime symptoms, they are often not well tolerated and have limited impact on long-term cardiovascular outcomes. As our understanding of the heterogenous factors driving OSA advances, novel therapies targeting specific physiological traits—such as arousal threshold, ventilatory instability, and upper airway muscle responsiveness—are being actively explored, with a promise to expand our therapeutic arsenal. Notably, the recent approval of tirzepatide for the treatment of obesity-related OSA marks a significant milestone in this evolving therapeutic landscape. This incretin-based drug, previously approved for diabetes and obesity management, offers dual benefits, promoting weight loss and improving OSA severity and symptoms. Given this therapeutic evolution in the OSA landscape over the last decade, this review provides a comprehensive overview of the current and emerging treatment strategies for personalized OSA management, with a particular emphasis on the growing role and promise of incretin-based therapies.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4255 - 4269"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688594","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":"When Primary Ciliary Dyskinesia Is Diagnosed in Utero: Insights from Two Families","authors":"Israel Amirav,&nbsp;Moria Beer,&nbsp;Dorit Redlich Amirav,&nbsp;Moran Lavie","doi":"10.1007/s12325-025-03298-1","DOIUrl":"10.1007/s12325-025-03298-1","url":null,"abstract":"<div><h3>Introduction</h3><p>Primary ciliary dyskinesia (PCD) is a rare genetic disorder affecting ciliary function, leading to chronic respiratory ilness. Prenatal diagnosis remains uncommon, with most cases identified postnatally through clinical symptoms and genetic testing. However, advancements in prenatal screening have enabled earlier detection, presenting parents with complex medical and ethical dilemmas. This study explores parental decision-making following such a diagnosis, identifying key influencing factors and highlighting the role of healthcare providers in offering informed guidance.</p><h3>Methods</h3><p>A qualitative approach was used to analyze the experiences of two families facing a prenatal PCD diagnosis. Semi-structured interviews were conducted and analyzed using Braun &amp; Clarke’s thematic framework. Discussions with families focused on their concerns, reasoning, and ultimate choices.</p><h3>Results</h3><p>Five key themes emerged: (1) trust in doctors—parental decisions were strongly influenced by medical professionals’ guidance; (2) quality of life—families considered both the child’s well-being and the impact on existing family dynamics; (3) fertility concerns—reproductive opportunities influenced urgency in decision-making; (4) imagined future—parents weighed the long-term implications of raising a child with PCD; (5) spiritual resources—cultural and spiritual beliefs provided emotional support.</p><h3>Conclusion</h3><p>Parental decision-making following a prenatal PCD diagnosis is multifaceted, shaped by medical, emotional, and ethical considerations. Our findings underscore the need for healthcare providers to offer comprehensive, individualized counseling that balances clinical expertise with empathetic support, empowering parents to make informed choices.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4696 - 4705"},"PeriodicalIF":4.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03298-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688596","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":"Ixekizumab Improves Signs, Symptoms, and Quality of Life in Patients with Axial Spondyloarthritis Irrespective of Symptom Duration","authors":"Victoria Navarro-Compán,&nbsp;John D. Reveille,&nbsp;Proton Rahman,&nbsp;José A. Maldonado-Cocco,&nbsp;Marina Magrey,&nbsp;Rebecca Bolce,&nbsp;Tommaso Panni,&nbsp;Andris Kronbergs,&nbsp;Martin Rudwaleit","doi":"10.1007/s12325-025-03305-5","DOIUrl":"10.1007/s12325-025-03305-5","url":null,"abstract":"<div><h3>Introduction</h3><p>The objective of this study was to assess treatment response to ixekizumab, an interleukin-17A antagonist, by shorter versus longer symptom duration (&lt; 5 years vs. ≥ 5 years) in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) up to 52 weeks.</p><h3>Methods</h3><p>This post hoc analysis used data from three randomized, placebo-controlled trials including patients with r-axSpA from COAST-V [biologic disease-modifying anti-rheumatic drug (bDMARD)-naïve] and COAST-W (tumor necrosis factor inhibitor-experienced) and patients with nr-axSpA from COAST-X (bDMARD-naïve). Patients received ixekizumab (80 mg every 2 or 4 weeks) or placebo through Week 16 and ixekizumab to Week 52. Assessments included the Assessment in SpondyloArthritis international Society 40% improvement (ASAS40) and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity [LDA (&lt; 2.1)] and Bath Ankylosing Spondylitis Disease Activity Index 50% improvement (BASDAI50) response rates through Week 52 and change from baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) at Week 16.</p><h3>Results</h3><p>Fewer patients treated with ixekizumab (pooled dosing) had shorter versus longer symptom duration [<i>n</i> = 33 vs. <i>n</i> = 306 (r-axSpA); <i>n</i> = 73 vs. <i>n</i> = 111 (nr-axSpA)]. Ixekizumab-treated patients with shorter versus longer symptom duration had numerically higher response rates at Week 16/Week 52 for ASAS40 [51.5/60.6 vs. 36.9/40.5 (r-axSpA); 42.5/54.8 vs. 36.0/41.4 (nr-axSpA)], ASDAS LDA [39.4/48.5 vs. 27.5/35.6 (r-axSpA); 32.9/49.3 vs. 27.9/36.9 (nr-axSpA)], and BASDAI50 [42.4/54.5 vs. 31.4/36.6 (r-axSpA); 38.4/49.3 vs. 27.9/34.2 (nr-axSpA)]. However, relative risk ratios at Week 16 did not significantly favor the shorter duration subgroup. Findings were comparable for SF-36 PCS at Week 16. The present findings should be interpreted in the context of small numbers of patients in some shorter duration subgroups.</p><h3>Conclusion</h3><p>Ixekizumab was shown to be efficacious in both patients with shorter or longer symptom duration and in r-axSpA or nr-axSpA.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov Identifiers, NCT02696785; NCT02696798; NCT02757352.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4706 - 4716"},"PeriodicalIF":4.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03305-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688593","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":"Bleeding-Related Hospitalizations Among Direct Oral Anticoagulant Users and Nonusers in Medicare Fee-For-Service: Variation in Prevalence, Burden, and Characteristics","authors":"Carol M. Bazell,&nbsp;Maggie N. Alston,&nbsp;Latha G. Ganti,&nbsp;Raymond C. Chang,&nbsp;H. Andrew Wilsey,&nbsp;Stephanie A. Leary,&nbsp;Winston C. Fopalan,&nbsp;Christopher W. Baugh","doi":"10.1007/s12325-025-03287-4","DOIUrl":"10.1007/s12325-025-03287-4","url":null,"abstract":"<div><h3>Introduction</h3><p>Bleeding-related hospitalizations represent a major burden for patients and the US healthcare system. Anticoagulant therapies pose a greater risk for bleeding, especially among the older Medicare population. Direct oral anticoagulants (DOACs) have become the most common type of oral anticoagulant used in Medicare due to their clinical advantages. This descriptive study examines the burden of bleeding-related hospitalizations among DOAC users and nonusers (with no evidence of anticoagulant or antiplatelet use) in Medicare fee-for-service (FFS).</p><h3>Methods</h3><p>This was an observational retrospective cohort study of bleeding-related hospitalizations in Medicare FFS using the 2020–2022 Medicare 100% Research Identifiable Files. We used 2020–2021 pharmacy claims to classify beneficiaries into DOAC user and nonuser cohorts and 2021–2022 healthcare administrative claims to identify demographics, bleeding-related hospitalization characteristics, and outcomes.</p><h3>Results</h3><p>Of 18.4 million Medicare FFS beneficiaries who met the study’s enrollment requirements, 9.3% were assigned to the DOAC user cohort, 81.5% were assigned to the nonuser cohort, and 9.1% were excluded (non-DOAC anticoagulant-only or prescription antiplatelet-only users). The bleeding-related hospitalization rate was four times higher in the DOAC user cohort compared to the nonuser cohort (27.5 and 6.7 per 1000 beneficiaries, respectively). Gastrointestinal bleeding was the most common bleed type leading to hospitalization in both DOAC user and nonuser cohorts (64.6% and 55.4%, respectively), followed by intracerebral hemorrhage (21.3% and 34.5%, respectively), and other types of bleeding (14.2% and 10.1%, respectively). Characteristics and outcomes were similar between cohorts, with variation largely related to bleeding type.</p><h3>Conclusion</h3><p>This study demonstrated variations in use of DOACs and characteristics of bleeding-related hospitalizations and identified higher rates of bleeding-related hospitalizations among DOAC users compared to nonusers. Hospitalization characteristics and outcomes differed by bleeding type. These findings highlight the Medicare FFS burden of bleeding-related hospitalizations and opportunities for the improved detection and management of bleeding, particularly among DOAC users.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"4916 - 4932"},"PeriodicalIF":4.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03287-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688590","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":"Patient-Reported Psychosocial Burdens and Quality of Life and Work Productivity Impacts Among Patients with Clinically Distinct Alopecia Areata Severity Profiles","authors":"Kent A. Hanson,&nbsp;Jenny Austin,&nbsp;Nicola Clayton,&nbsp;Peter Anderson,&nbsp;Sergio Vano-Galvan,&nbsp;Simran Marwaha,&nbsp;Samantha K. Kurosky,&nbsp;Alexandre Lejeune,&nbsp;James Piercy,&nbsp;Ernest H. Law","doi":"10.1007/s12325-025-03302-8","DOIUrl":"10.1007/s12325-025-03302-8","url":null,"abstract":"<div><h3>Introduction</h3><p>Alopecia areata (AA) may negatively impact patient quality of life (QoL), disease perception, and work productivity. AA severity is not solely based on scalp hair loss; individuals with AA can experience psychosocial burdens, including emotional symptoms and activity limitations (ES/AL). Our objective was to identify discrete AA severity profiles and evaluate the association with patient-reported outcomes (PROs).</p><h3>Methods</h3><p>Dermatologist and patient surveys from the Alopecia Areata Disease Specific Programme in France, Germany, Italy, Spain, and the United Kingdom were analyzed. PRO instruments included the Alopecia Areata Patient Priority Outcomes (AAPPO), Work Productivity Activity Index—AA, Skindex-16 AA, Patient Satisfaction with Hair Growth (P-Sat), and Hospital Anxiety and Depression Scale (HADS). Latent class analysis identified distinct classes using the AAPPO hair loss, ES, and AL response options.</p><h3>Results</h3><p>A 5-class model was selected. Each class exhibited distinct profiles based on patient-reported hair loss and ES/AL burden: (1) very mild hair loss, very mild ES/AL (<i>n</i> = 175); (2) mild hair loss, mild ES/AL (<i>n</i> = 165); (3) moderate hair loss, very severe ES/AL (<i>n</i> = 111); (4) severe hair loss, moderate ES/AL (<i>n</i> = 52); and (5) very severe hair loss, severe ES/AL (<i>n</i> = 33). Class 3 reported significantly more overall work impairment [<i>β</i> = 16.3 (95% CI, 7.8–24.7)] than class 1. Overall Skindex-16 AA scores were highest for class 3 [<i>β</i> = 38.7 (95% CI, 33.3–44.2)]. Class 3 reported significantly more HADS anxiety [<i>β</i> = 6.0 (95% CI, 4.9–7.0)] and depression [<i>β</i> = 5.7 (95% CI, 4.6–6.9)] than class 1. Across all P-Sat domains, class 5 reported the least satisfaction with therapy.</p><h3>Conclusion</h3><p>Generally, patients with more severe patient-reported hair loss and ES/AL had decreased QoL and satisfaction with care and greater work productivity impairment. Although class 3 had moderate patient-reported hair loss, patients experienced the most severe ES/AL burden, suggesting that AA impacts well-being and daily activities in patients with less extensive hair loss.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4556 - 4570"},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03302-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673737","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":"Pharmacokinetics and Safety of Ripretinib in Participants with Hepatic Impairment: A Phase 1 Study","authors":"Anna Papinska,&nbsp;Lakshmi Viswanathan,&nbsp;Qiang Lu,&nbsp;Farida Abane,&nbsp;Charles Psoinos,&nbsp;Rodrigo Ruiz-Soto","doi":"10.1007/s12325-025-03307-3","DOIUrl":"10.1007/s12325-025-03307-3","url":null,"abstract":"<div><h3>Introduction</h3><p>Ripretinib, an oral switch-control inhibitor of KIT tyrosine kinase and platelet-derived growth factor receptor alpha kinase, is approved for adults with advanced gastrointestinal stromal tumor who received prior treatment with three or more kinase inhibitors, including imatinib. Ripretinib is metabolized into the equally active major metabolite DP-5439, a prominent component of total drug exposure in humans after oral administration. Ripretinib and DP-5439 undergo hepatic metabolism mainly via cytochrome P450 3A4. Therefore, exposure to ripretinib and/or DP-5439 may be affected in patients with hepatic impairment.</p><h3>Methods</h3><p>This is a phase 1, open-label study evaluating the pharmacokinetics and safety of ripretinib and DP-5439 in participants with varying degrees of hepatic impairment compared with matched healthy participants after a single oral 50-mg ripretinib dose.</p><h3>Results</h3><p>Mild hepatic impairment did not affect exposure to ripretinib and DP-5439. In participants with moderate and severe hepatic impairment, ripretinib exposure (area under the concentration–time curve) was 99% and 163% greater, respectively, compared with matched healthy participants, whereas DP-5439 exposure was approximately 20% greater in moderate and 44% lower in severe hepatic impairment. Exposure to combined ripretinib + DP-5439 was higher by approximately 51% and 37% in participants with moderate and severe hepatic impairment, respectively. No safety signals were identified.</p><h3>Conclusion</h3><p>On the basis of the known safety profile of ripretinib, these increased ripretinib and combined ripretinib + DP-5439 exposures in participants with hepatic impairment are unlikely to be clinically relevant. Therefore, no dose adjustments are recommended for patients with gastrointestinal stromal tumor and hepatic impairment.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4540 - 4555"},"PeriodicalIF":4.0,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03307-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666726","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":"Use of Patient-Reported Outcome Measures in Patients with Rheumatoid Arthritis in Spain and Barriers to Implementation: A Delphi Study","authors":"Esteban Rubio,&nbsp;Mª. José Moreno,&nbsp;Adela Gallego,&nbsp;Isabel Castrejón,&nbsp;Amelia Cobo,&nbsp;Sebastián Moyano,&nbsp;Marta Comellas","doi":"10.1007/s12325-025-03300-w","DOIUrl":"10.1007/s12325-025-03300-w","url":null,"abstract":"<div><h3>Introduction</h3><p>This study aimed to investigate the pattern of use and barriers for implementation of patient-reported outcomes measures (PROMs) in patients with rheumatoid arthritis (RA) in Spain. </p><h3>Methods</h3><p>Two-round Delphi study targeted at rheumatologists attending a PROMs training program and guided by a Scientific Committee composed of four expert rheumatologists was conducted. The survey assessed the current use, appropriateness, and feasibility of 7 PROMs proposed by the International Consortium for Health Outcomes Measurements (ICHOM). Barriers to implement PROMs in routine care were also explored. A 7-point Likert scale was used ranging from 1 (strongly disagree) to 7 (strongly agree). Consensus was established when &gt; 75% reached agreement (rated 6–7 = agreement, or 1–2 = disagreement).</p><h3>Results</h3><p>A total of 39 rheumatologists of 120 (32%) participated {61.5% women; mean age 50.3 [standard deviation (SD) 11.0] years; mean 18.1 (9.6) years of experience; 23.1% running a RA clinic}. Although 82.1% of rheumatologists agreed on involving patients in shared decision-making (SDM), only 56.4% adopted SDM strategies in treatment decisions. A higher percentage (79.4%) agreed on the importance of incorporating PROMs, but only 28.2% recognized to use them in routine care, being the most frequently used pain on a visual analogue scale (VAS) (89.8%), the Health Assessment Questionnaire (HAQ) (71.7%), and a VAS-fatigue (66.7%). The remaining proposed PROMs by ICHOM did not reach a consensus on either appropriateness or feasibility. The main barriers found included lack of time in consultation (84.6%) and the unavailability of PROMs platforms incorporated in the electronic medical records (87.9%). </p><h3>Conclusion</h3><p>Spanish rheumatologists consider PROMs useful to guide SDM in routine care being the most frequently used pain, fatigue, and physical function. However, other domains proposed by ICHOM as health-related quality of life (HRQoL) or work/school productivity are not commonly used. Promoting the use of PROMs strategies, including optimizing consultation time and incorporating PROMs into electronic medical records, is necessary.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"4904 - 4915"},"PeriodicalIF":4.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03300-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658136","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}