Advances in Therapy最新文献

{"title":"Onset and Long-Term Maintenance of Optimal Itch Response in Adult Patients with Moderate-to-Severe Atopic Dermatitis Treated with Dupilumab: Post Hoc Analysis from Two Phase 3 Trials.","authors":"Sonja Ständer, Gil Yosipovitch, Eric L Simpson, Brian S Kim, Kenji Kabashima, Diamant Thaçi, Martin Metz, Zhen Chen, Sandra Hagen, Mike Bastian","doi":"10.1007/s12325-025-03124-8","DOIUrl":"https://doi.org/10.1007/s12325-025-03124-8","url":null,"abstract":"<p><strong>Introduction: </strong>The treat-to-target concept established goals to guide treatment with systemic therapies in atopic dermatitis (AD), including goals for itch improvement, reported as the most burdensome symptom. The aim of this study is to assess optimal itch response onset and long-term maintenance using treat-to-target criteria in dupilumab-treated patients.</p><p><strong>Methods: </strong>This post hoc analysis assessed patients ≥ 18 years with moderate-to-severe AD in two phase 3, randomized, double-blind, placebo-controlled studies. Patients received dupilumab 300 mg every 2 weeks or placebo with concomitant topical corticosteroids (TCS) for 52 weeks (CHRONOS); or dupilumab monotherapy 300 mg every week/every 2 weeks/every 4 weeks/every 8 weeks or placebo for 36 weeks after achieving Eczema Area and Severity Index improvement of 75% or Investigator's Global Assessment 0/1 with dupilumab in SOLO1/2 (SOLO-CONTINUE). Optimal itch response was defined as Peak Pruritus Numeric Rating Scale ≤ 4.</p><p><strong>Results: </strong>Patients receiving dupilumab + TCS achieved optimal itch response faster and in higher proportion than those receiving placebo + TCS (P < 0.0001) and maintained optimal response longer (median [Q1-Q3] 40 [11-50] vs 3 [0-23] weeks; P < 0.0001). Patients achieving optimal itch response with dupilumab monotherapy who continued treatment maintained response longer compared with those transitioned to placebo, although duration decreased with less frequent dosing (P < 0.0001 for all dupilumab regimens vs placebo).</p><p><strong>Conclusion: </strong>Optimal itch response was achieved rapidly and maintained long term in adult patients treated with dupilumab with or without concomitant TCS therapy.</p><p><strong>Trial registration: </strong>NCT02395133 and NCT02260986.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447875","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":"LymphoTEC: a Retrospective Real-World Study on Lymphocyte Reconstitution After Lymphopenia in Patients with Multiple Sclerosis Treated with Dimethyl Fumarate in France.","authors":"Jérôme de Sèze, Pierre Labauge, Roland Liblau, Mikel Martinez, Thibault Moreau, Laurent Suchet, Patrick Vermersch, Sandra Vukusic, Guillaume Mathey, Laure Michel, Jonathan Ciron, Aurelie Ruet, Elisabeth Maillart, Helene Zephir, Caroline Papeix, Gilles Defer, Mikael Cohen, David Axel Laplaud, Eric Berger, Pierre Clavelou, Eric Thouvenot, Olivier Heinzlef, Jean Pelletier, Claire Giannesini, Olivier Casez, Bertrand Bourre, Abir Wahab, Laurent Magy, Jean-Philippe Camdessanché, Inès Doghri, Céline Labeyrie, Karolina Hankiewicz, Jean-Philippe Neau, Corinne Pottier, Pamela Dobay, Hanyue Li, Seth Levin, Marilyn Gros, Marta Ruiz, Fabien Rollot","doi":"10.1007/s12325-024-03092-5","DOIUrl":"https://doi.org/10.1007/s12325-024-03092-5","url":null,"abstract":"<p><strong>Introduction: </strong>Dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Some patients may develop lymphopenia on DMF; therefore, LymphoTEC evaluated absolute lymphocyte count (ALC) reconstitution after DMF discontinuation.</p><p><strong>Methods: </strong>LymphoTEC was a retrospective, multicenter study of patients with RRMS in the Observatoire Français de la Sclérose en Plaques registry. Times to ALC reconstitution and lymphopenia were estimated by the Kaplan-Meier method. Univariate and multivariate analyses evaluated factors associated with ALC reconstitution after DMF discontinuation or lymphopenia after DMF initiation. Patients treated with DMF for ≥ 3 months with ≥ 1 ALC in the 6 months before/close to DMF initiation and ≥ 1 ALC during treatment were included.</p><p><strong>Results: </strong>Overall, 1429 RRMS patients were included; 356 patients developed lymphopenia, of whom 183 discontinued DMF. Overall, ALC decreased by 33% over the first year and plateaued thereafter. The probability of developing lymphopenia was 18.2% after 1 year. In patients with lymphopenia, median times to ALC reconstitution after DMF discontinuation were 3.8 months overall, 4.0 months for Grade 1 lymphopenia, 3.0 months for Grade 2, and 9.7 months for Grade 3. At 12 months, 83.0% had reconstituted ALC. In DMF discontinuers, median time to discontinuation was 1.2 years. There was no increased risk of serious or opportunistic infections in patients with lymphopenia. No cases of progressive multifocal leukoencephalopathy were reported. First ALC reconstitution after DMF discontinuation was associated with diabetes, DMF duration, DMF duration before lymphopenia, and DMF duration after lymphopenia; first lymphopenia after DMF initiation was associated with age and ALC at DMF initiation.</p><p><strong>Conclusion: </strong>LymphoTEC confirms previous reports on DMF-induced lymphopenia; the benefit-risk profile of DMF remains favorable. Most cases of lymphopenia were not severe and ALC reconstitution typically occurred within 4 months of DMF discontinuation. Patients with shorter and milder lymphopenia had faster ALC reconstitution.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT04756687.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447938","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 Following Biologic Initiation in US Patients with Chronic Rhinosinusitis with Nasal Polyps.","authors":"Anju Peters, Xiaohui Zhao, Aimee M Near, Joseph Han, Joseph D Spahn, Sze-Jung S Wu, Andrew W Lindsley, Tham T Le, Elizabeth J Wang, Rifat Tuly, Inyoung Lee, Christopher S Ambrose","doi":"10.1007/s12325-025-03120-y","DOIUrl":"https://doi.org/10.1007/s12325-025-03120-y","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic rhinosinusitis with nasal polyposis (CRSwNP) is often associated with persistent symptoms and impaired quality of life despite treatment with intranasal corticosteroids. Biologics (dupilumab, mepolizumab, omalizumab) have been recently approved for CRSwNP. This study aims to characterize biologic use and real-world outcomes, including medication use and nasal polyps (NP) surgeries, following biologic treatment in US patients with CRSwNP.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed linked data from IQVIA longitudinal prescription and medical claims databases (July 2018-June 2023). Patients evaluated included those with ≥ 2 diagnoses of CRSwNP and ≥ 12 months of baseline data (overall cohort, index = first observed CRSwNP diagnosis) as well as patients with CRSwNP who received ≥ 2 consecutive biologic doses and had ≥ 24 months of follow-up data (biologic cohort, index = first biologic).</p><p><strong>Results: </strong>Of 74,480 patients with CRSwNP, 8716 (12.0%) received a biologic and 2208 met all inclusion criteria. Dupilumab was the most frequently received biologic (89.8%; mepolizumab, 5.3%; omalizumab, 4.8%). Relative to the overall cohort, the biologic cohort was younger (mean age: 52.6 vs. 57.6 years), had more women (54.0% vs. 46.1%) and had a higher baseline prevalence of asthma (72.4% vs. 30.9%), allergic rhinitis (70.6% vs. 37.4%), NP surgery (15.8% vs. 5.8%), oral corticosteroid (OCS) use (84.0% vs. 51.8%), and antibiotic use (84.2% vs. 68.7%). During the 24 months after biologic initiation, 65.6% of patients had ≥ 1 OCS use (≥ 2 OCS uses during months 1-12, 27.0%; during months 13-24, 27.0%) and 77.9% had ≥ 1 antibiotic use; and 7.1% of patients without NP surgery before biologic initiation had ≥ 1 NP surgery during follow-up. Almost half of patients (49.3%) discontinued (≥ 90 days without receipt) their initial biologic during follow-up.</p><p><strong>Conclusion: </strong>Biologic use was relatively low among US patients with CRSwNP. OCS and antibiotic usage among patients with CRSwNP remained substantial despite use of currently approved biologics, indicating an unmet need for improved treatment options.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447990","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":"Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD): Back to the Future.","authors":"Giordano Fiorentù, Nicol Bernardinello, Giacomo Giulianelli, Elisabetta Cocconcelli, Elisabetta Balestro, Paolo Spagnolo","doi":"10.1007/s12325-025-03129-3","DOIUrl":"https://doi.org/10.1007/s12325-025-03129-3","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a progressive syndrome characterized by increased pulmonary artery pressure. PH often complicates chronic lung diseases, thus contributing to a substantial disease burden and poor prognosis. The WHO Group 3 Pulmonary Hypertension has many subcategories, including sleep-hypoventilation PH, high altitude-PH, chronic obstructive pulmonary disease (COPD)-PH, and interstitial lung disease (PH-ILD), the latter carrying the worst prognosis. ILD is a heterogeneous group of disorders characterized by cough and shortness of breath and, in progressive forms, irreversible loss of function and respiratory failure. The development of PH in patients with ILD worsens exercise capacity and exertional dyspnea and impairs quality of life. Thus, suspicion and early detection of PH following thorough cardiologic evaluation (i.e., echocardiography, pro-BNP, and right heart catheterization) is paramount for appropriate patient management. For PH secondary to chronic respiratory diseases, current guidelines recommend optimizing the treatment of the underlying respiratory condition and offering long-term oxygen therapy. In recent years, several clinical trials have failed to identify drugs beneficial for group 3 PH. Conversely, the INCREASE trial of inhaled treprostinil has recently provided hope for treating PH-ILD. In this review, we summarize and critically discuss the present and future of the pharmacological management of PH-ILD.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447989","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":"Motor Function and Safety of Nusinersen and Risdiplam in Asian Patients with Types 2-4 Spinal Muscular Atrophy (SMA): A Systematic Review and Meta-Analysis.","authors":"Xinran Zhao, Yihan Liao, Jingyu Zhao, Lin Zhu, Jun Liu, Min Zhang, Wei Li","doi":"10.1007/s12325-024-03101-7","DOIUrl":"https://doi.org/10.1007/s12325-024-03101-7","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to systematically appraise and synthesize real-world data of motor function and safety in Asian patients with spinal muscular atrophy (SMA) treated with nusinersen or risdiplam.</p><p><strong>Methods: </strong>This study systematically searched PubMed, Cochrane, Embase, CNKI, and Wanfang databases for real-world studies (RWS) published from January 2017 to January 2024. Based on the prespecified study selection and eligibility criteria, RWS evaluating motor function and/or safety outcomes in patients with types 2-4 SMA treated with nusinersen or risdiplam were included, while studies without Asian populations were excluded. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias, and a meta-analysis was conducted for each motor function endpoint based on the extracted data.</p><p><strong>Results: </strong>A total of 26 RWS were included in this review, of which 17 reporting main motor function outcomes were included in the meta-analyses. Intervention in all 17 studies was nusinersen; none included risdiplam. Statistically significant improvement was observed in Revised Upper Limb Module (RULM) [Mean difference (MD) = 2.27 (0.84, 3.71)], Hammersmith Functional Motor Scale Expanded (HFMSE) [MD = 2.62 (1.79, 3.45)] and six-minute walk test (6MWT) [MD = 18.29 (9.12, 27.45)] when treated with nusinersen ≤ 6 months and > 6 months (HFMSE [MD = 4.34 (3.54, 5.14)]; 6MWT [MD = 45.59 (12.92, 78.27)]). Clinically meaningful responses of motor milestones were also observed when treating nusinersen over 6 months: 54.4% (0.305, 0.772) for RULM, 53.0% (0.273, 0.779) for HFMSE and 97.1% (0.819, 1.000) for 6MWT. A total of 19 studies addressed safety outcomes. Reported adverse events were consistent with the expected safety profile for nusinersen.</p><p><strong>Conclusion: </strong>Our study suggests that nusinersen is associated with a statistically significant and clinically meaningful motor function improvement in Asian patients with types 2-4 SMA in the real-world setting. No unexpected safety concern was observed for nusinersen. Motor function and safety outcomes after risdiplam could not be evaluated in this patient population under real-world settings due to limited studies.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439518","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":"Surgical Outcomes of Baerveldt Glaucoma Implant Versus Ahmed Glaucoma Valve in Neovascular Glaucoma: A Retrospective Multicenter Study.","authors":"Kentaro Iwasaki, Sachi Kojima, Ryotaro Wajima, Akira Matsuda, Koki Yoshida, Aika Tsutsui, Michihiro Kono, Miho Nozaki, Koji Namiguchi, Keisuke Nitta, Yusaku Miura, Toshihiro Inoue, Tomomi Higashide, Kyoko Ishida, Masaki Tanito, Masaru Inatani","doi":"10.1007/s12325-025-03128-4","DOIUrl":"https://doi.org/10.1007/s12325-025-03128-4","url":null,"abstract":"<p><strong>Introduction: </strong>This multicenter retrospective study compared the surgical outcomes of Baerveldt glaucoma implant (BGI) surgery with those of Ahmed glaucoma valve (AGV) surgery in patients with neovascular glaucoma (NVG).</p><p><strong>Methods: </strong>The study included patients with NVG aged ≥ 20 years who had undergone BGI (223 eyes) or AGV (146 eyes) surgery between April 1, 2012 and December 31, 2021 across 10 clinical centers in Japan. Surgical success or failure was the primary outcome measure of this study. We defined surgical failure as a reduction of < 20% in the pre-operative intraocular pressure (IOP) or criterion A (IOP > 21 mmHg), criterion B (IOP > 17 mmHg), or criterion C (IOP > 14 mmHg). In addition, we considered a requirement for re-operation, loss of light perception, and hypotony as surgical failure.</p><p><strong>Results: </strong>The surgical success rate of the BGI surgery group was significantly higher than that of the AGV group for criteria A (P = 0.01) and B (P = 0.01). Multivariate analysis revealed that AGV surgery showed significant associations with surgical failure for criteria A (hazard ratio, 1.74), B (hazard ratio, 1.72), and C (hazard ratio, 1.34). The overall incidence of postoperative complications was comparable between the two groups. The requirement for re-operation in the AGV surgery group was significantly higher than that in the BGI surgery group (12.3% vs. 5.8%, P = 0.03).</p><p><strong>Conclusions: </strong>BGI surgery yielded a higher success rate than AGV surgery in patients with NVG for a target IOP of < 21 or < 17 mmHg. No significant differences were observed between the two procedures in terms of the incidence of postoperative complications. Additional glaucoma surgery was required more frequently following AGV surgery. Therefore, BGI surgery may be a more suitable and efficacious option for the management of IOP in patients with neovascular glaucoma compared with AGV surgery.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439521","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":"Liver-Kidney-Metabolic Health, Sex, and Menopause Impact Total Scores and Monovessel vs. Multivessel Coronary Artery Calcification.","authors":"Kamran Bagheri Lankarani, Mohamad Jamalinia, Fatemeh Zare, Seyed Taghi Heydari, Ali Ardekani, Amedeo Lonardo","doi":"10.1007/s12325-025-03121-x","DOIUrl":"https://doi.org/10.1007/s12325-025-03121-x","url":null,"abstract":"<p><strong>Introduction: </strong>Liver-kidney-metabolic health (LKMH) depends on complex interactions between metabolic dysfunction-associated steatotic liver disease (MASLD), chronic kidney disease (CKD), sex, and reproductive status. This study evaluates in a holistic manner how LKMH, sex, and menopause influence coronary artery calcification (CAC) burden.</p><p><strong>Methods: </strong>Patients without previous cardiovascular disease were prospectively recruited. Liver fat was assessed via ultrasonography and categorized as mild or moderate-to-severe. CKD was classified using estimated glomerular filtration rate (eGFR). CAC burden was quantified as 0, 1-299, ≥ 300, single-vessel, or multivessel with coronary computed tomography. Stepwise backward multinomial logistic regression was applied for analysis.</p><p><strong>Results: </strong>A total of 446 patients (59.2% female, average age 52.9 years) were included. Moderate-to-severe MASLD was independently associated with an increased risk of CAC 1-299 [OR 2.30 (1.21-4.36)], CAC ≥ 300 [OR 4.93 (1.46-16.59)], and single-vessel CAC [OR 2.03 (1.03-4.00)]. Mild MASLD [OR 2.47 (1.20-4.21)], moderate-to-severe MASLD [OR 3.74 (1.76-7.93)], and CKD stage 2 [OR 2.27 (1.26-4.08)] were independently associated with increased multivessel CAC risk. Liver fat content showed a dose-response association with CAC burden. Subgroup analysis revealed that MASLD and CKD increased CAC risk in male but not female patients, with menopause significantly modifying LKMH's effect.</p><p><strong>Conclusion: </strong>LKMH's impact on CAC burden is significantly influenced by liver fat content, eGFR, sex, and menopause, suggesting that MASLD, CKD, sex, and reproductive status should be integrated into CAC risk prediction models.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412870","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":"No-Transcatheter Aortic Valve Replacement (TAVR) Zones and Their Effect on Access to Care for Medicare Beneficiaries with Aortic Stenosis.","authors":"Guy David, Andrew J Epstein, Jay Giri, Ashwin Nathan, Soumya G Chikermane, Michael Ryan, Christin Thompson, Seth Clancy, Candace Gunnarsson","doi":"10.1007/s12325-025-03116-8","DOIUrl":"https://doi.org/10.1007/s12325-025-03116-8","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the impact of geographic and socioeconomic barriers on access to transcatheter aortic valve replacement (TAVR).</p><p><strong>Methods: </strong>Utilizing Medicare data from the US Centers for Medicare and Medicaid Services, this study analyzed TAVR and surgical aortic valve replacement (SAVR) procedures among beneficiaries from 2017 to 2022. Geographic units were defined by 5-digit zip codes, categorized on the basis of TAVR/SAVR volume into four categories: (1) no TAVR or SAVR, (2) no-TAVR zone (SAVR present, no TAVR), (3) low-TAVR zone (TAVR/SAVR ratio ≤ 0.5), and (4) TAVR accessible (TAVR/SAVR ratio > 0.5). The differential distance index (DDI) was developed to measure travel hurdles, calculated as the difference in miles from a patient's zip code center to the treatment hospital (TAVR versus SAVR, CABG (coronary artery bypass grafting), and PCI (percutaneous coronary intervention) comparators). This study maintained a continuous access variable to model outcomes such as the ratio or volume of TAVR/SAVR and the percentage share of TAVR/AVR within each zip code over biennial periods (2017-2018, 2019-2020, 2021-2022). Covariates in the model included population density, area deprivation index (ADI), and calendar time, with an exploration of the interaction between DDI and ADI.</p><p><strong>Results: </strong>The analysis revealed significant geographic disparities in TAVR access across the USA, with no-TAVR zone and low-TAVR zone areas often featuring lower population densities, higher ADIs, and more rural settings. Increased travel distance (DDI) significantly correlated with lower TAVR utilization, emphasizing distance as a critical barrier. Furthermore, both ADI and DDI emerged as significant predictors of TAVR volume and share, underlining the compound effect of socioeconomic status and geographic distance on healthcare access.</p><p><strong>Conclusions: </strong>This study highlights the critical role of geographic and socioeconomic barriers in accessing advanced medical treatments like TAVR. Addressing these barriers may ensure equitable healthcare distribution, guiding policymakers and providers towards more accessible healthcare solutions for all populations.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405404","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":"Phase I Study to Evaluate the Effect of Hepatic Impairment on Pharmacokinetics and Safety of Tegoprazan, a Potassium Competitive Acid Blocker","authors":"Anhye Kim,&nbsp;Dongseong Shin,&nbsp;Youlim Seo,&nbsp;Deborah Kang,&nbsp;Yang Won Min,&nbsp;In Hee Kim,&nbsp;Jungryul Kim","doi":"10.1007/s12325-025-03127-5","DOIUrl":"10.1007/s12325-025-03127-5","url":null,"abstract":"<div><h3>Introduction</h3><p>Tegoprazan is a potassium-competitive acid blocker, and its systemic exposure is presumably affected by hepatic clearance and bioavailability. This study aimed to investigate the effect of hepatic impairment (HI) on the safety and pharmacokinetics of tegoprazan and metabolite.</p><h3>Methods</h3><p>An open-label, multicenter, parallel-group study was conducted in patients with mild (<i>n</i> = 8), moderate (<i>n</i> = 8) and severe (<i>n</i> = 1) HI according to the Child–Pugh classification as well as controls. Healthy subjects (<i>n</i> = 8) were matched to patients with the moderate category based on age, body mass index and sex. Blood and urine samples were obtained to evaluate the concentrations of tegoprazan and metabolite (M1) until 48 h after a single oral administration of 50 mg of tegoprazan.</p><h3>Results</h3><p>The geometric mean ratio with a 90% confidence interval of maximum plasma concentration and area under the plasma concentration–time curve for tegoprazan in patients with impaired hepatic function compared to controls were 0.8228 (0.4997–1.3550) and 1.2264 (0.7447–2.0197) in the mild category, 1.0332 (0.6274–1.7015) and 1.7676 (1.0733–2.9109) in the moderate category, and 1.0699 (0.3713–3.0823) and 1.9567 (0.6792–5.6377) in the severe category. The half-life, apparent clearance, renal clearance, and fraction unbound to plasma protein were comparable across study groups. The plasma concentration of M1 increased and decreased faster in the normal group. Tegoprazan was generally well tolerated in patients with HI.</p><h3>Conclusions</h3><p>Systemic exposure to tegoprazan tended to be increased in subjects with HI. The difference between patients with mild HI and the controls was deemed not to require dose adjustment for tegoprazan.</p><h3>Clinical Trial Registration</h3><p>ClinicalTrials.gov identifiers: NCT04494269 (31 Jul 2020).</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 3","pages":"1570 - 1581"},"PeriodicalIF":3.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389867","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":"Repeated Switching Between CT-P17 and EU Reference Adalimumab in Patients with Moderate-to-Severe Chronic Plaque Psoriasis: A Randomized, Double-Blind, Active-Controlled, Phase 3, Interchangeability Study","authors":"Mark G. Lebwohl,&nbsp;John Y. Koo,&nbsp;Janusz Jaworski,&nbsp;Jakub Trefler,&nbsp;Stefan Daniluk,&nbsp;Anna Dudek,&nbsp;Wojciech Baran,&nbsp;Witold Owczarek,&nbsp;Joanna Kolinek,&nbsp;Paweł Brzewski,&nbsp;Mariusz Sikora,&nbsp;Marek Krogulec,&nbsp;SungHyun Kim,&nbsp;YunJu Bae,&nbsp;DaBee Jeon,&nbsp;EunJin Choi,&nbsp;JungBin Cha,&nbsp;HyunJin Lee,&nbsp;SuJin Choi,&nbsp;David M. Pariser","doi":"10.1007/s12325-024-03100-8","DOIUrl":"10.1007/s12325-024-03100-8","url":null,"abstract":"<div><h3>Introduction</h3><p>This study aimed to demonstrate the interchangeability of biosimilar CT-P17 and European Union reference adalimumab (EU-adalimumab) in a repeated-switch scenario.</p><h3>Methods</h3><p>In this ongoing, randomized, double-blind, active-controlled, phase 3 study, adults with moderate-to-severe plaque psoriasis received 80 mg EU-adalimumab on day 1, then 40 mg 1 week later and every other week until week 11. At week 13, patients were randomized (1:1, via an interactive web response system) to continue EU-adalimumab (“continuous” group) or undergo repeated switches between CT-P17 and EU-adalimumab (“switching” group). Dosing was via subcutaneous administration. The primary endpoints were area under the concentration–time curve and maximum serum concentration between weeks 25 and 27 (AUC_tau,W25–27 and <i>C</i>_max,W25–27, respectively). Secondary endpoints comprised additional pharmacokinetic (PK) parameters, efficacy, safety, and immunogenicity. Week 27 findings are presented.</p><h3>Results</h3><p>The first patient provided signed informed consent on November 7, 2022. Week 27 visits were completed by August 14, 2023. Of 367 patients enrolled, 346 were randomized (switching group, <i>n</i> = 172; continuous group, <i>n</i> = 174). The ratios of least squares means between groups and associated 90% confidence intervals (CIs) for AUC_tau,W25–27 and <i>C</i>_max,W25–27 were 99.45% (94.11–105.08%) and 100.45% (95.03–106.17%), respectively. For both endpoints, 90% CIs fell within the predefined equivalence margin of 80–125% and criteria were greater than calculated <i>t</i> values, satisfying bioequivalence. Additional PK endpoints and efficacy, safety, and immunogenicity findings were similar between groups. Safety profiles were in line with those previously reported.</p><h3>Conclusions</h3><p>Week 27 primary PK results demonstrated bioequivalence, and the overall study results supported the interchangeability of CT-P17 and EU-adalimumab.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov, NCT05495568.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 3","pages":"1582 - 1599"},"PeriodicalIF":3.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03100-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389869","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}