Advances in Therapy最新文献

{"title":"Comparative Effectiveness of Fluticasone Furoate/Umeclidinium/Vilanterol and Budesonide/Glycopyrrolate/Formoterol Fumarate among US Patients with Chronic Obstructive Pulmonary Disease","authors":"David Mannino,&nbsp;Stephen Weng,&nbsp;Guillaume Germain,&nbsp;Julien Boudreau,&nbsp;Anabelle Tardif-Samson,&nbsp;Sergio Forero-Schwanhaeuser,&nbsp;François Laliberté,&nbsp;Patrick Gravelle,&nbsp;Chris H. Compton,&nbsp;Stephen G. Noorduyn,&nbsp;Rosirene Paczkowski","doi":"10.1007/s12325-024-03088-1","DOIUrl":"10.1007/s12325-024-03088-1","url":null,"abstract":"<div><h3>Introduction</h3><p>Chronic obstructive pulmonary disease (COPD) is associated with exacerbations which can reduce quality of life and increase mortality. Single-inhaler triple therapy (SITT) is recommended for maintenance treatment of COPD among patients experiencing exacerbations despite dual-therapy use. This real-world comparative effectiveness study compared the impact of SITTs, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM), on COPD exacerbations and mortality.</p><h3>Methods</h3><p>Medicare Fee-for-Service (FFS) patients with COPD initiated on FF/UMEC/VI or BUD/GLY/FORM were identified from the Komodo Research healthcare claims dataset (01/01/2016–12/31/2023). Overlap weighting based on high-dimensional propensity scores evaluated from patient characteristics was used to adjust for baseline confounding. Primary outcome was annualized rate of moderate–severe COPD exacerbations (per patient-year; PPY) compared using rate ratios (RRs) with 95% confidence intervals (CIs) from weighted Poisson regression models. Secondary and exploratory outcomes were risk of moderate–severe COPD exacerbations and all-cause mortality, respectively, evaluated using Kaplan–Meier analysis and hazard ratios (HR) with 95% CIs from Cox proportional hazard models. A secondary analysis was conducted among a mutually exclusive population with Medicare Advantage, Medicaid, or commercial insurance.</p><h3>Results</h3><p>Overall, 32,312 FF/UMEC/VI and 12,230 BUD/GLY/FORM Medicare FFS patients were included. After weighting, median follow-up was 9 months. Compared with BUD/GLY/FORM, FF/UMEC/VI users had a 12% lower rate of annualized moderate–severe COPD exacerbations [0.80 and 0.91 PPY; RR (95% CI): 0.88 (0.85–0.92); <i>P</i> &lt; 0.001] and a 10% lower risk of moderate–severe exacerbations at 12 months post-initiation [HR (95% CI): 0.90 (0.87–0.93); <i>P</i> &lt; 0.001], driven by moderate exacerbations. FF/UMEC/VI compared with BUD/GLY/FORM users had 11% lower risk of all-cause mortality at 12 months post-initiation [5.6% vs. 6.4%; HR (95% CI): 0.89 (0.80–0.98); <i>P</i> = 0.020]. Results were consistent among patients with Medicare Advantage, Medicaid, or commercial insurance.</p><h3>Conclusions</h3><p>In this real-world comparative effectiveness study, FF/UMEC/VI was associated with significantly lower rate and risk of COPD exacerbations than BUD/GLY/FORM.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1131 - 1146"},"PeriodicalIF":3.4,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03088-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891354","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":"Simplified Approach to Managing Newly Diagnosed Patients with Mild-to-Moderate Hypertension in Routine Clinical Practice","authors":"Stella S. Daskalopoulou,&nbsp;Helena Papacostas-Quintanilla,&nbsp;Romualda Brzozowska-Villatte,&nbsp;on behalf of the Study Investigators","doi":"10.1007/s12325-024-03091-6","DOIUrl":"10.1007/s12325-024-03091-6","url":null,"abstract":"<div><h3>Introduction</h3><p>The aim of the observational SIMPLE study was to assess real-life effectiveness and safety of a single-pill combination (SPC) of perindopril arginine/amlodipine in a broad range of subjects with newly diagnosed mild-to-moderate hypertension treated in Canadian general practice.</p><h3>Methods</h3><p>Treatment-naïve participants aged 18–65 years with mild-to-moderate hypertension, whose physicians decided to initiate the perindopril/amlodipine SPC, were recruited from Canadian clinical practice from October 2017 to February 2019. Participants were followed at 3- (M3) and 6-month (M6) visits after treatment initiation. The recommended starting dose of 3.5 mg/2.5 mg once daily was up-titrated, at the discretion of the treating physician, if blood pressure (BP) remained above target at subsequent visits. The primary endpoint was change in mean office systolic BP (SBP) and diastolic BP (DBP) at M6.</p><h3>Results</h3><p>The full analysis set included 1179 participants with a mean age of 51.5 ± 8.7 years; 61% were male. Mean SBP/DBP at baseline was 153.4 ± 11.5/94.8 ± 7.7 mmHg. Treatment was initiated at 3.5 mg/2.5 mg in 76.0% participants. Over the 6-month treatment period, significant (<i>P</i> &lt; 0.001) decreases from baseline were observed for SBP (− 22.9 ± 14.5 mmHg) and DBP (− 13.4 ± 9.1 mmHg), with 70.2% of participants achieving their BP target. Across all perindopril/amlodipine SPC dose groups, 61.4% of participants achieved BP targets at M3; mean SBP was reduced by 20.8 ± 14.7 mmHg and DBP by 11.7 ± 9.2 mmHg (both <i>P</i> &lt; 0.001). Analysis by baseline subgroup revealed significant BP reductions across age groups, sex, hypertension grades, and diabetes status. Participants with Grade 2 hypertension had a significantly greater decrease than those with Grade 1 (<i>P</i> &lt; 0.001). Treatment with the SPC was well tolerated, and in the 6.1% with treatment-related adverse events, the majority were mild to moderate. High (99%) self-reported adherence (&lt; 20 missed doses) in the 49.4% with available data and high physician satisfaction with treatment (82%) were reported.</p><h3>Conclusion</h3><p>Data from routine Canadian clinical practice indicate that a perindopril/amlodipine SPC is associated with significant BP reductions from baseline in a broad range of participants with different cardiovascular risk factors and may represent an appropriate first-line treatment for subjects with newly diagnosed hypertension.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1108 - 1130"},"PeriodicalIF":3.4,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03091-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891355","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":"Clinical Features and Current Pharmacotherapy of OAB in Practice: Ideal and Reality","authors":"Kazuna Tsubouchi,&nbsp;Hisatomi Arima,&nbsp;Taiki Emoto,&nbsp;Hiroshi Nakazawa,&nbsp;Takahiro Kitano,&nbsp;Masashi Mikami,&nbsp;Chikao Aoyagi,&nbsp;Hiroshi Matsuzaki,&nbsp;Kosuke Tominaga,&nbsp;Naotaka Gunge,&nbsp;Takeshi Miyazaki,&nbsp;Yu Okabe,&nbsp;Nobuyuki Nakamura,&nbsp;Yuichiro Fukuhara,&nbsp;Masahiro Tachibana,&nbsp;Chizuru Nakagawa,&nbsp;Fumihiro Yamazaki,&nbsp;Nobuhiro Haga","doi":"10.1007/s12325-024-03070-x","DOIUrl":"10.1007/s12325-024-03070-x","url":null,"abstract":"<div><h3>Introduction</h3><p>The present study aimed to investigate the prescribing patterns of anticholinergics (anti-AChR) or β3-adrenergic agonists (β₃A) in the pharmacotherapy of overactive bladder (OAB) and to evaluate the differences in the frequency of adverse events (AEs) between the two types of drugs using a large-scale medical claims database.</p><h3>Methods</h3><p>This cohort study was conducted using the JMDC claims database between May 2015 and April 2023. Patient characteristics, prescription and treatment patterns of anti-AChR and β₃A, and the incidence of AEs have been described.</p><h3>Results</h3><p>Overall, 70,936 patients were analyzed [mean age, 53.6 (standard deviation: 12.3) years]. Among women (48.5%; 34,439), 21.4% initially received anti-AChR and 27.2% received β₃A; among men (51.5%; 36,497), 17.1% initially received anti-AChR and 34.3% received β₃A. Most patients (79.6%; women, 83.5%; men, 75.8%) visited clinics. About 10% of patients had a treatment change: 5.6% switched the drug type (change from anti-AChR to β₃A or vice versa), and 4.0% had an add-on of another drug type. The incidence rate of treatment change per 100 patient-years was higher with β₃A in both women (12.39) and men (13.65). In the multivariable analysis, initial prescription with anti-AChR compared with β₃A did not show any association with the risk of AEs.</p><h3>Conclusion</h3><p>This large-scale database study revealed that treatment for OAB is often initiated with β₃A and prescribed mainly at clinics. Changes or additions to initial prescriptions were as low as about 5%, indicating that raising awareness among physicians treating OAB is particularly important to improve the quality of life of patients with OAB. Our study also showed that the incidence of AEs was not associated with the initially prescribed drug type. Continued exploration is warranted to further clarify the risk of AEs with each prescription.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1094 - 1107"},"PeriodicalIF":3.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03070-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885214","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":"Real-World Safety, Tolerability and Effectiveness of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis: Final Report of Post-marketing Surveillance in Japan","authors":"Yoshikazu Inoue,&nbsp;Takashi Ogura,&nbsp;Arata Azuma,&nbsp;Yasuhiro Kondoh,&nbsp;Sakae Homma,&nbsp;Kenya Muraishi,&nbsp;Rie Ikeda,&nbsp;Kaori Ochiai,&nbsp;Yukihiko Sugiyama,&nbsp;Toshihiro Nukiwa","doi":"10.1007/s12325-024-03079-2","DOIUrl":"10.1007/s12325-024-03079-2","url":null,"abstract":"<div><h3>Introduction</h3><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia, which is characterised by progressive worsening of dyspnoea and lung function. Nintedanib treatment is recommended to slow IPF disease progression. The aim of this post-marketing surveillance (PMS) study was to evaluate the safety and effectiveness of nintedanib over 24 months in patients with IPF in a real-world setting in Japan.</p><h3>Methods</h3><p>This prospective, non-interventional, all-case PMS study of nintedanib included Japanese patients with IPF who started nintedanib between 7 October 2015 and 2 May 2023. The primary outcome was to determine the proportion of patients with adverse drug reactions (ADRs), and the secondary outcome was the adjusted absolute change from baseline in forced vital capacity (FVC) at 24 months.</p><h3>Results</h3><p>In total, 5717 patients from 1013 institutions were included in the safety analysis (mean ± standard deviation age 71.7 ± 8.1 years, 78.1% male, 70.8% current or former smokers). Most patients (83.9%) had initiated nintedanib at a dose of 150 mg capsules twice daily. At 24 months, 2841 patients (64.8%) had discontinued nintedanib, mainly due to adverse events (44.0%), ADRs (24.1%) or insufficient effectiveness (5.7%). The most common ADRs were diarrhoea (35.5%), hepatic function abnormal (14.4%), decreased appetite (9.9%), liver disorders (7.8%) and nausea (5.8%). The adjusted absolute mean change in FVC from baseline to 24 months was − 212.3 mL (95% confidence interval − 235.3, − 189.3).</p><h3>Conclusion</h3><p>This is the largest prospective study to investigate patients with IPF who were treated with nintedanib. The safety and effectiveness of nintedanib treatment in this real-world setting of Japanese patients with IPF was similar to that reported in previous studies. Nintedanib effectively slowed the progression of IPF. No new safety concerns were identified, and the need for appropriate management of hepatic disorders and diarrhoea (as per the approved product information) was confirmed.</p><h3>Study Registration</h3><p>ClinicalTrials.gov (NCT02607722)/European Union electronic register of Post-Authorisation Studies (EUPAS10891).</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1075 - 1093"},"PeriodicalIF":3.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03079-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875971","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":"Medicare Advantage Population in the United States: Outcomes of Patients with Asthma Treated with ICS/LABA Before and After Initiation with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)","authors":"Alan P. Baptist,&nbsp;Guillaume Germain,&nbsp;Jacob Klimek,&nbsp;François Laliberté,&nbsp;Robert C. Schell,&nbsp;Sergio Forero-Schwanhaeuser,&nbsp;Alison Moore,&nbsp;Stephen G. Noorduyn,&nbsp;Rosirene Paczkowski","doi":"10.1007/s12325-024-03083-6","DOIUrl":"10.1007/s12325-024-03083-6","url":null,"abstract":"<div><h3>Introduction</h3><p>The clinical benefits of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) have been demonstrated in clinical trials. There is limited evidence regarding the effectiveness and economic outcomes associated with FF/UMEC/VI use in US clinical practice. This real-world study assessed asthma-related exacerbations, healthcare resource utilization (HRU), and healthcare costs among a Medicare Advantage-insured population before and after initiation of FF/UMEC/VI in patients with asthma previously treated with an inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA).</p><h3>Methods</h3><p>De-identified data were obtained from the Komodo Health database (01/01/2016–12/31/2023) for adults with asthma who received prior ICS/LABA treatment and had ≥ 12 months of continuous Medicare Advantage coverage both pre- and post-FF/UMEC/VI initiation (index date). Rates of asthma-related exacerbations and HRU were compared using rate ratios (RR) from Poisson regressions. Healthcare costs were calculated per patient per year (PPPY) and compared using mean cost differences from generalized linear models.</p><h3>Results</h3><p>In total, 2598 Medicare Advantage-insured patients who initiated FF/UMEC/VI for asthma were included. The mean ± SD age was 67.9 ± 12.3 years; 75.5% were female. The rate of overall asthma-related exacerbations was 31% lower in the post- versus pre-initiation period (RR 0.69; 95% CI 0.65, 0.73; <i>p</i> &lt; 0.001) and included a 24% lower rate of inpatient/emergency department (IP/ED)-defined exacerbations (RR 0.76; 95% CI 0.68, 0.85; <i>p</i> &lt; 0.001) and a 34% lower rate of systemic corticosteroid (SCS)-defined exacerbations (RR 0.66; 95% CI 0.61, 0.71; <i>p</i> &lt; 0.001). Asthma-related ED visits (RR 0.69; 95% CI 0.60, 0.80; <i>p</i> &lt; 0.001) and asthma-related outpatient (OP) visits (RR 0.77; 95% CI 0.71, 0.84; <i>p</i> &lt; 0.001) were both lower, and the mean reduction in cost was $411 PPPY (95% CI $575, $248; <i>p</i> &lt; 0.001), after FF/UMEC/VI initiation.</p><h3>Conclusions</h3><p>Initiation of FF/UMEC/VI after ICS/LABA treatment among Medicare Advantage-insured patients with asthma was associated with reduced rates of asthma-related exacerbations, ED and OP visits, and healthcare costs, highlighting the benefits of therapy escalation among this patient population.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1061 - 1074"},"PeriodicalIF":3.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03083-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875961","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":"An Access-Focused Patient-Centric Value Assessment Framework for Medication Formulary Decision-Making in Immune-Mediated Inflammatory Diseases","authors":"Min Yang,&nbsp;Manish Mittal,&nbsp;A. Mark Fendrick,&nbsp;Diana Brixner,&nbsp;Bruce W. Sherman,&nbsp;Yifei Liu,&nbsp;Pankaj Patel,&nbsp;Jerry Clewell,&nbsp;Qing Liu,&nbsp;Louis P. Garrison Jr.","doi":"10.1007/s12325-024-03076-5","DOIUrl":"10.1007/s12325-024-03076-5","url":null,"abstract":"<div><p>The healthcare system in the United States (US) is complex and often fragmented across national and regional health plans which exhibit substantial variability in benefit design and formulary policies for accessing medications. We propose an access-focused value assessment framework for formulary decision-making for medications to manage immune-mediated inflammatory diseases (IMIDs), where patients are at the center of this framework. Formulary decision-making for IMID medications can be a challenging, even daunting, task with continuously evolving and enhanced treat-to-target goals. Given the complexity of the US healthcare system, patients and their caregivers need assurance from formulary decision-makers that rapid, predictable, and sustained access to both well-established treatments and innovative therapies will be a priority, with a particular emphasis on continuity of effective care. This <u>a</u>ccess-focused <u>pa</u>tient-<u>c</u>entric (APAC) value assessment approach encompasses three “value components”—higher therapeutic goals, better health-related quality of life, and improved work productivity—the monetization of which can be derived using data from clinical trials when real-world data are yet to become available. Measures and assessment approaches are outlined to serve as a pragmatic tool for decision-makers in the US to ensure timely delivery and sustained access of clinically indicated therapies aimed to improve patient outcomes, enhance equity, and increase efficiency.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"568 - 578"},"PeriodicalIF":3.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03076-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863162","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":"Population Pharmacokinetics of Trofinetide in a Pediatric Population Aged 2–4 Years with Rett Syndrome","authors":"Mona Darwish,&nbsp;Julie Passarell,&nbsp;Kelly Maxwell,&nbsp;Heather Bradley,&nbsp;Kathie M. Bishop,&nbsp;James M. Youakim","doi":"10.1007/s12325-024-03058-7","DOIUrl":"10.1007/s12325-024-03058-7","url":null,"abstract":"<div><h3>Introduction</h3><p>Weight-banded trofinetide dosing improved physician- and caregiver-rated efficacy measures and had acceptable tolerability in patients aged 2‒4 years (DAFFODIL study) and 5‒20 years (LAVENDER study) with Rett syndrome (RTT). Selection of weight-banded dosing regimens for these studies was based on population pharmacokinetic (popPK) modeling and exposure simulations. This study applied an updated popPK model to confirm steady-state trofinetide exposures achieved in DAFFODIL patients were within target range.</p><h3>Methods</h3><p>A popPK model was developed using data from 14 clinical studies of trofinetide in healthy volunteers and pediatric and adult patients, including the LAVENDER and DAFFODIL studies. Individual exposure measures (area under concentration–time curve over 0–12 h [AUC_0–12] were generated via integration of the predicted concentration–time profile for each DAFFODIL study participant based on the popPK model and individual empiric Bayesian pharmacokinetic parameter estimates. Distributions of steady-state AUC_0–12 values for each body-weight group were compared against target exposure (AUC_0–12 = 800‒1200 µg·h/mL).</p><h3>Results</h3><p>Distribution and box plots of simulated steady-state AUC_0–12 values achieved with the weight-banded DAFFODIL dosing regimen used in younger individuals aged 2–4 years with RTT (twice daily trofinetide 5 g [≥ 9 to &lt; 12 kg] or 6 g [≥ 12 to &lt; 20 kg]) indicated good overlap with the target exposure range. Median steady-state AUC_0–12 values for both body-weight bands fell within the target exposure range.</p><h3>Conclusions</h3><p>PopPK model-based simulations confirm that the weight-banded dosing regimen used in DAFFODIL is adequate to achieve target trofinetide exposure in 2- to 4-year-olds with RTT.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1009 - 1025"},"PeriodicalIF":3.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03058-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845589","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":"Population Pharmacokinetic Modeling to Support Trofinetide Dosing for the Treatment of Rett Syndrome","authors":"Mona Darwish,&nbsp;Julie Passarell,&nbsp;Kelly Maxwell,&nbsp;James M. Youakim,&nbsp;Heather Bradley,&nbsp;Kathie M. Bishop","doi":"10.1007/s12325-024-03056-9","DOIUrl":"10.1007/s12325-024-03056-9","url":null,"abstract":"<div><h3>Introduction</h3><p>Oral trofinetide administered using a body weight-banded dosing regimen was approved in the US for the treatment of Rett syndrome (RTT) in patients aged ≥ 2 years. This approval was principally based on efficacy and safety findings of the phase 3 LAVENDER study in girls and women aged 5–20 years with RTT and extended to younger children aged 2–4 years with supporting data from the DAFFODIL study. Weight-banded dosing regimens were selected based on early clinical population pharmacokinetic (popPK) modeling and different scenario simulations. We report the development and application of an updated popPK model to confirm that steady-state trofinetide exposures achieved in individual patients in the LAVENDER study were within target exposure range.</p><h3>Methods</h3><p>A previously developed popPK model using data from nine clinical studies was updated based on 13 clinical studies of trofinetide in healthy volunteers and pediatric and adult patients, including the LAVENDER study. PopPK model and empiric individual Bayesian pharmacokinetic parameter estimates were used to generate trofinetide exposures. Covariate data from the pharmacokinetic dataset from LAVENDER study subjects (<i>n</i> = 92) were used to estimate individual steady-state trofinetide exposure (area under concentration–time curve over 0–12 h [AUC_0–12]). Steady-state exposures in individual patients in the LAVENDER study were used to confirm that the dosing regimens resulted in exposures within the target range.</p><h3>Results</h3><p>Among 5- to 20-year-olds receiving the LAVENDER BID dosing regimen [trofinetide 6 g (12‒20 kg), 8 g (&gt; 20‒35 kg), 10 g (&gt; 35‒50 kg), and 12 g (&gt; 50 kg)], simulated AUC_0-12 values overlapped with the target exposure range; median AUC_0–12 values were within target exposure range for all weight bands.</p><h3>Conclusions</h3><p>PopPK model-based simulations confirm that weight-banded trofinetide dosing used in LAVENDER in girls and women aged 5–20 years with RTT achieved target exposure.</p><p>Graphical abstract available for this article.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1026 - 1043"},"PeriodicalIF":3.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03056-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845588","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":"The Urgency Numeric Rating Scale: Psychometric Evaluation in Adults with Crohn’s Disease","authors":"Marla Dubinsky,&nbsp;Aisha Vadhariya,&nbsp;Sylvia Su,&nbsp;Xian Zhou,&nbsp;Frederick Durand,&nbsp;Claudine Clucas,&nbsp;Larissa Stassek,&nbsp;Ariane K. Kawata,&nbsp;Simon Travis","doi":"10.1007/s12325-024-03081-8","DOIUrl":"10.1007/s12325-024-03081-8","url":null,"abstract":"<div><h3>Introduction</h3><p>Bowel urgency has recently been recognized as a Crohn’s disease (CD) symptom that substantially impacts patients’ quality of life. The Urgency NRS is a single-item patient-reported outcome measure assessing bowel urgency severity in the past 24 h (0–10 scale). We aimed to evaluate the psychometric properties of the Urgency Numeric Rating Scale (NRS) in adults with moderately to severely active CD and to estimate thresholds for meaningful improvement and bowel urgency remission.</p><h3>Methods</h3><p>Psychometric analyses used pooled data from the Phase 3 VIVID-1 study of mirikizumab, where participants with CD completed the Urgency NRS and other assessments. The Patient Global Rating of Severity (PGRS) and Patient Global Impression of Change (PGIC) were used as primary anchors to estimate Urgency NRS thresholds representing meaningful improvement and remission.</p><h3>Results</h3><p>The Urgency NRS showed good test–retest reliability in participants who were stable based on PGRS and PGIC. It was moderately correlated with similar assessments and weakly correlated with endoscopic/laboratory assessments. It differentiated between participant subgroups varying in disease severity and quality of life based on PGRS and other assessments. It was sensitive to change, as Urgency NRS improvements during the trial differed between most PGRS change and PGIC categories. A 3–5-point reduction on the Urgency NRS represented meaningful improvement and a score of ≤ 2 represented remission.</p><h3>Conclusion</h3><p>The Urgency NRS demonstrated strong psychometric properties in the VIVID-1 population of moderately to severely active CD. Analyses also suggested meaningful improvement and remission thresholds.</p><h3>Trial Registration</h3><p>Clinicaltrials.gov, NCT03926130. Registered 23 April 2019, https://clinicaltrials.gov/study/NCT03926130.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"1044 - 1060"},"PeriodicalIF":3.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03081-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845591","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":"Cost-Effectiveness Analysis of Finerenone for Treatment of Chronic Kidney Disease in Patients with Type 2 Diabetes from Japanese Payer Perspective","authors":"Ataru Igarashi,&nbsp;Kenichi Ohara,&nbsp;Hiroyuki Matsuda,&nbsp;Junko Morii,&nbsp;Suchitra Jagannathan,&nbsp;Ronald Filomeno","doi":"10.1007/s12325-024-03084-5","DOIUrl":"10.1007/s12325-024-03084-5","url":null,"abstract":"<div><h3>Introduction</h3><p>Type 2 diabetes (T2D) is a major cause of chronic kidney disease (CKD) in Japan, and there is an increasing treatment need for first- and second-line care in these patients. The addition of finerenone to current treatment modalities lowers the risk of CKD progression and cardiovascular events in patients with CKD and T2D from the Japanese payer perspective. This study investigated the cost-effectiveness analysis of adding finerenone to standard of care (SoC) versus SoC alone for the treatment of CKD in patients with T2D.</p><h3>Methods</h3><p>The FINE-CKD model validated to estimate the cost-effectiveness of finerenone uses the Markov model to simulate the disease pathway of patients over a lifetime horizon. The model was adapted to reflect the Japanese payer perspective and estimated incremental costs, utilities, and incremental cost-effectiveness ratios (ICERs). Sensitivity and scenario analyses were performed to evaluate the effect of the uncertainty of each parameter using a robust model.</p><h3>Results</h3><p>The quality-adjusted life years (QALYs) for finerenone and SoC were estimated at 9.39 and 9.25, respectively, with an incremental QALY for finerenone for SoC of 0.14. The total cost of finerenone was estimated at ¥ 8,912,601, at an incremental cost of ¥ 274,052, leading to an ICER of ¥ 1,959,516 per QALY gained compared with SoC alone.</p><h3>Conclusion</h3><p>Finerenone in conjunction with SoC is a more cost-effective treatment alternative to SoC alone for adult patients with CKD and T2D from a Japanese healthcare payer perspective.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 2","pages":"995 - 1008"},"PeriodicalIF":3.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-03084-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833301","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}