Advances in Therapy最新文献

{"title":"The Correlation Between Body Mass Index and Health-Related Quality of Life: Data from Two Weight Loss Intervention Studies","authors":"Pavol Kral,&nbsp;Thomas Holst-Hansen,&nbsp;Anamaria V. Olivieri,&nbsp;Cristina Ivanescu,&nbsp;Mark Lamotte,&nbsp;Sara Larsen","doi":"10.1007/s12325-024-02932-8","DOIUrl":"10.1007/s12325-024-02932-8","url":null,"abstract":"<div><h3>Introduction</h3><p>The correlation between body mass index (BMI) and utility in participants with obesity was assessed using health-related quality-of-life data collected in two weight loss intervention studies, SCALE and STEP 1.</p><h3>Methods</h3><p>Short Form Health Survey 36-Item (SF-36) scores from SCALE and STEP 1 were mapped to EuroQoL-5 dimensions-3 levels (EQ-5D-3L) using an established algorithm to derive utilities for the UK. SF-36 scores from STEP 1 were converted into Short Form 6 dimension (SF-6D) utilities for Portugal using the tool developed by the University of Sheffield. The correlation between baseline BMI and utility was assessed by multiple linear regression analyses, controlling for demographic and clinical parameters.</p><h3>Results</h3><p>A higher baseline BMI correlated with lower EQ-5D-3L and SF-6D utilities, although the trend was non-significant. Assuming linearity between BMI ranges 30–40 kg/m², an additional unit of BMI correlated with 0.0041 and 0.0031 lower EQ-5D-3L scores in SCALE and 0.0039 and 0.0047 lower EQ-5D-3L and 0.0027 and 0.0020 lower SF-6D scores in STEP 1 for men and women, respectively.</p><h3>Conclusion</h3><p>In individuals with comparable demographic characteristics and weight-related comorbidities, a 1 unit change in BMI leads to a difference of up to 0.005 in utility indices.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov identifiers: SCALE (NCT01272219) and STEP 1 (NCT03548935).</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02932-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306947","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 Cost-Effectiveness Analysis of Axicabtagene Ciloleucel versus Tisagenlecleucel in the Treatment of Diffuse Large B-cell Lymphoma Based on a Real-World French Registry","authors":"Markqayne Ray,&nbsp;Jean-Gabriel Castaigne,&nbsp;Alexandra Zang,&nbsp;Anik Patel,&nbsp;Elizabeth Hancock,&nbsp;Nicholas Brighton,&nbsp;Emmanuel Bachy","doi":"10.1007/s12325-024-02971-1","DOIUrl":"10.1007/s12325-024-02971-1","url":null,"abstract":"<div><h3>Introduction</h3><p>Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor T-cell therapies that were evaluated in third and later line (3L+) relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the ZUMA-1 and JULIET trials, respectively. As of October 2021, the DESCAR-T registry included 729 French patients with 3L+ r/r DLBCL who received axi-cel or tisa-cel. Using these data, propensity score matching was used to conduct an adjusted comparison between axi-cel and tisa-cel. Axi-cel was associated with statistically significant improvements in overall survival (OS) and progression-free survival (PFS), and significantly more frequent Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS), compared with tisa-cel. There was no significant difference in Grade ≥ 3 cytokine release syndrome (CRS). The current analysis assessed the cost-effectiveness of axi-cel versus tisa-cel in the treatment of 3L+ r/r DLBCL using propensity score-matched data from the DESCAR-T registry.</p><h3>Methods</h3><p>A partitioned survival model was used to extrapolate costs and quality-adjusted life years (QALYs) over a lifetime. Survival curves for PFS and OS were based on independent mixture cure models fitted to digitized Kaplan–Meier data for the propensity score-matched DESCAR-T populations. Average duration of intensive care unit stays for each of axi-cel and tisa-cel in DESCAR-T were used to inform adverse event costs. Selected parametric survival distributions were based on clinical expert validation. Utility values were derived from ZUMA-1, and costs were obtained from French registries and published sources. List prices were used for both axi-cel and tisa-cel. Costs and outcomes were discounted at an annual rate of 2.5%.</p><h3>Results</h3><p>Axi-cel is associated with an incremental cost-effectiveness ratio of €15,520 per QALY compared with tisa-cel.</p><h3>Conclusion</h3><p>Based on explicit willingness-to-pay thresholds applied in Europe, axi-cel is expected to be a cost-effective use of healthcare resources in real-world clinical settings compared with tisa-cel in 3L+ r/r DLBCL.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306942","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":"Progression from Non-alcoholic Steatohepatitis to Advanced Liver Diseases and Mortality Among Medicare Patients","authors":"Yestle Kim,&nbsp;Joe Medicis,&nbsp;Matthew Davis,&nbsp;Dominic Nunag,&nbsp;Robert Gish","doi":"10.1007/s12325-024-02979-7","DOIUrl":"10.1007/s12325-024-02979-7","url":null,"abstract":"<div><h3>Introduction</h3><p>Non-alcoholic steatohepatitis (NASH) may progress to more advanced liver disease. This study aimed to characterize NASH progression and mortality in the Medicare population.</p><h3>Methods</h3><p>Patients with NASH in 100% Medicare fee-for-service claims accrued from 2015–2021 who were ≥ 66 years old at index diagnosis, continuously enrolled for ≥ 12 months prior to and ≥ 6 months following index (unless death), and had no evidence of other causes of liver disease were included. Diagnosis codes defined severity states: non-cirrhotic NASH, compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver transplant (LT). Survival analyses of disease progression and mortality were conducted for each state and by year of progression (Y1–5). Cox proportional hazards models assessed risk factors of worsening disease.</p><h3>Results</h3><p>Mean age and follow-up were 72.2 and 2.8 years in 14,806 unique patients (<i>n</i> = 12,990 NASH; 1899 CC; 997 DCC; 209 HCC; 140 LT). Progression rates were highest for patients with CC (11–37% for Y1–5), followed by DCC (3–18%), NASH (3–12%), and HCC (2–4%). Mortality rates were highest for patients with HCC (41–85% for Y1–5), followed by DCC (41–76%), LT (7–33%), CC (6–26%), and NASH (2–12%). Patients with any disease progression had a 5-year mortality rate more than double that of patients without progression (41% vs. 16%).</p><p>Delayed progression from NASH was associated with lower mortality risk; the 5-year mortality rate was 26% lower for patients with progression in Y2 vs. Y1 (32% vs. 43%) and further decreased for progression in Y3-Y5. Risk factors included age, nursing home use, congestive heart failure, coagulopathy, fluid/electrolyte disorders, and unexplained weight loss.</p><h3>Conclusion</h3><p>Medicare patients ≥ 66 years with NASH experience high risk of disease progression associated with increased mortality rates. Slower disease progression is associated with lower mortality rates, suggesting that therapies that can delay or prevent NASH progression may reduce morbidity and mortality.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02979-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306946","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":"PIONEER REAL UK: A Multi-Centre, Prospective, Real-World Study of Once-Daily Oral Semaglutide Use in Adults with Type 2 Diabetes","authors":"Ponnusamy Saravanan,&nbsp;Heather Bell,&nbsp;Uffe Christian Braae,&nbsp;Edward Collins,&nbsp;Alisa Deinega,&nbsp;Ketan Dhatariya,&nbsp;Alena Machell,&nbsp;Antonia Trent,&nbsp;Anna Strzelecka","doi":"10.1007/s12325-024-02973-z","DOIUrl":"10.1007/s12325-024-02973-z","url":null,"abstract":"<div><h3>Introduction</h3><p>Oral semaglutide provides an alternative to injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treatment of type 2 diabetes (T2D). The PIONEER REAL studies evaluate clinical outcomes of oral semaglutide treatment of T2D in a real-world setting. PIONEER REAL UK focused on adults living with T2D in the UK.</p><h3>Methods</h3><p>The multi-centre, prospective and non-interventional single-arm study enrolled 333 participants and followed them for 34–44 weeks. Participants were treated as part of routine clinical practice and had not been previously treated with injectable glucose-lowering medication. The primary endpoint was change in glycated haemoglobin (HbA_1C) from baseline to end of study (EOS). Secondary endpoints included change in body weight, proportion of participants with HbA_1C &lt; 7% (53 mmol/mol) at EOS and proportion of participants with ≥ 1%-point HbA_1C reduction and body weight reduction of ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ) status and change.</p><h3>Results</h3><p>Of 333 participants, 299 completed the study and 227 were on treatment at EOS. People treated with oral semaglutide experienced significantly reduced HbA_1C by an estimated change of – 1.1%-points (95% CI – 1.27 to – 0.96; <i>P</i> &lt; 0.0001) or – 12.2 mmol/mol (CI – 13.87 to – 10.47; <i>P</i> &lt; 0.0001). Estimated change in body weight was – 4.8 kg (CI – 5.47 to – 4.12; <i>P</i> &lt; 0.0001). At EOS, an HbA_1C level &lt; 7% (53 mmol/mol) was recorded in 46.3% of participants. A ≥ 1%-point reduction in HbA_1C combined with a ≥ 3% reduction in body weight was observed in 36.4% of participants, and 27.1% had a ≥ 1%-point reduction in HbA_1C and a ≥ 5% body weight reduction. Treatment satisfaction improved significantly during the study. No new safety concerns or cases of severe hypoglycaemia were reported.</p><h3>Conclusion</h3><p>People living with T2D in the UK experienced a meaningful decrease in HbA_1C and body weight after initiation of oral semaglutide treatment. No new safety issues were observed.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov: NCT04862923.</p><p>Graphical plain language summary available for this article.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02973-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306945","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":"Macitentan and Tadalafil Combination Therapy in Incident and Prevalent Pulmonary Arterial Hypertension: Real-World Evidence from the OPUS/OrPHeUS Studies","authors":"Kelly M. Chin,&nbsp;Richard Channick,&nbsp;Nick H. Kim,&nbsp;Gwen MacDonald,&nbsp;Rose Ong,&nbsp;Nicolas Martin,&nbsp;Assunta Senatore,&nbsp;Vallerie V. McLaughlin","doi":"10.1007/s12325-024-02964-0","DOIUrl":"10.1007/s12325-024-02964-0","url":null,"abstract":"<div><h3>Introduction</h3><p>Historically, patients recently (≤ 6 months) diagnosed with pulmonary arterial hypertension (PAH; incident) have had poorer survival than those with a longer (&gt; 6 months) time from PAH diagnosis (prevalent). Despite guideline recommendations for initial combination therapy for most patients with PAH, many are initiated and maintained on monotherapy. Real-world evidence to evaluate the benefit of early combination treatment in newly-diagnosed patients is lacking.</p><h3>Methods</h3><p>Patients with PAH initiating combination therapy with the endothelin receptor antagonist macitentan and the phosphodiesterase-5 inhibitor tadalafil (M+T) were identified from the combined dataset of the US, multicenter OPUS (prospective, observational drug registry; NCT02126943) and OrPHeUS (retrospective, medical chart review; NCT03197688) studies (2013–2020). Descriptive analyses were performed for the incident and prevalent cohorts, as well as the subcohort of incident patients who received M+T as first-line combination therapy (incident initial combination).</p><h3>Results</h3><p>In OPUS/OrPHeUS, 1336 patients with PAH received M+T during the observation period. For the incident [<i>n</i> = 453 (33.9%)], incident initial combination [<i>n</i> = 272 (20.4%)], and prevalent [<i>n</i> = 837 (62.6%)] cohorts: median (Q1, Q3) M+T exposure was 14.2 (4.2, 27.5), 12.2 (3.2, 25.5), and 14.7 (4.5, 28.0) months. 12-month Kaplan–Meier estimates (95% confidence limits) for survival were 91.2% (87.7, 93.7), 88.5% (83.2, 92.2), and 92.9% (90.6, 94.6), for patients free from hospitalization were 59.4% (54.1, 64.4), 56.3% (49.1, 62.9), and 62.3% (58.5, 65.9), and for patients persisting on combination therapy were 68.6% (63.9, 72.8), 65.0% (58.8, 70.6) and 66.9% (63.5, 70.0). Adverse events (OPUS only) were reported in 77.8%, 80.2%, and 80.3% of patients, respectively, with no unexpected adverse events observed.</p><h3>Conclusions</h3><p>Despite a historically worse prognosis, incident patients receiving M+T, including as initial combination therapy, had similar survival and hospitalization as prevalent patients. Safety profiles were similar across cohorts. Together, these data support the use of early combination therapy with macitentan and tadalafil.</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":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02964-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306944","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":"Key Challenges to Understanding the Burden of Respiratory Syncytial Virus in Older Adults in Southeast Asia, the Middle East, and North Africa: An Expert Perspective","authors":"Hakan Günen,&nbsp;Ashraf Alzaabi,&nbsp;Abdelaziz Bakhatar,&nbsp;Sana Al Mutairi,&nbsp;Kittipong Maneechotesuwan,&nbsp;Daniel Tan,&nbsp;Mohammed Zeitouni,&nbsp;Bhumika Aggarwal,&nbsp;Arnas Berzanskis,&nbsp;Otávio Cintra","doi":"10.1007/s12325-024-02954-2","DOIUrl":"10.1007/s12325-024-02954-2","url":null,"abstract":"<div><h3>Introduction</h3><p>Respiratory syncytial virus (RSV) is a common, highly contagious pathogen and a leading cause of serious illness among infants and older adults. While existing scientific evidence has predominantly focused on the epidemiology and disease burden of RSV in infants, data in older adults remain limited in some countries, including those in Southeast Asia (SEA) and the Middle East and North Africa (MENA) region. Here, we outline the key challenges for understanding the burden of RSV in older adults in SEA and the MENA region and we propose opportunities for improving understanding and eventually reducing the impact of RSV.</p><h3>Main Findings and Conclusions</h3><p>A key challenge identified by the expert group, particularly in older adults, is a lack of awareness (among healthcare professionals, policy makers, and the public) of RSV burden and the associated risks for severe outcomes. This is often confounded by the complexities of underdiagnosis, surveillance limitations, and comorbidities. To address these issues, we suggest medical education initiatives for physicians in SEA and the MENA region to better understand the need to protect older adults from RSV, and encourage more widespread routine testing to better understand the burden of RSV. We also recommend surveillance studies in these regions to provide comprehensive and accurate epidemiological data on RSV in older adults. Finally, in the absence of current surveillance data in these regions, we propose extrapolating existing global data and local pediatric data to inform the likely burden of RSV in older adults.</p><p>A graphical abstract is available with 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":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02954-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278964","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":"Summary of Research: Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan","authors":"Navdeep Tangri,&nbsp;Anjay Rastogi,&nbsp;Tadashi Sofue","doi":"10.1007/s12325-024-02961-3","DOIUrl":"10.1007/s12325-024-02961-3","url":null,"abstract":"<div><p>This is a summary of the original article ‘Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan’. The slowing down of kidney function decline is important for managing chronic kidney disease (CKD) and preventing its complications. Clinical trials of dapagliflozin, a sodium–glucose cotransporter-2 inhibitor (SGLT-2i), have shown reductions in disease progression and death in patients with CKD and elevated levels of albuminuria. This summary of research provides an overview of a previously published article that aimed to find out whether dapagliflozin is also effective in patients with lower levels of albuminuria [urinary albumin-to-creatinine ratio (UACR) below 200 mg/g]. Starting dapagliflozin was associated with slower kidney function decline in patients with CKD and UACR below 200 mg/g compared with not starting. This effect was also observed in a subgroup analysis of patients without type 2 diabetes. These results suggest that the established benefits of SGLT-2is may extend to patients with lower levels of albuminuria.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02961-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249094","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 Cost-Utility Analysis of Ferric Derisomaltose Versus Ferric Carboxymaltose in Patients with Iron Deficiency Anemia in China","authors":"Fengkui Zhang,&nbsp;Aizong Shen,&nbsp;Waqas Ahmed,&nbsp;Richard F. Pollock","doi":"10.1007/s12325-024-02987-7","DOIUrl":"10.1007/s12325-024-02987-7","url":null,"abstract":"<div><h3>Introduction</h3><p>Intravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) unresponsive to oral iron treatment, in whom oral iron is contraindicated, or where rapid iron replenishment is required. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost–utility of FDI versus FCM in a population of patients with IDA in China.</p><h3>Methods</h3><p>A previously-published patient-level simulation model was used to model the cost–utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with body weight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life were obtained from SF-36v2 data from the PHOSPHARE-IBD RCT.</p><h3>Results</h3><p>Over the 5-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 vs. 6.79). This resulted in iron procurement and administration cost savings of renminbi (RMB) 206 with FDI (RMB 3,519 vs. RMB 3,312). Reduced incidence of hypophosphatemia-related fatigue resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over 5 years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention.</p><h3>Conclusions</h3><p>The results showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02987-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249114","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":"Estimation of the Eligible Population For Resmetirom Among Adults in the United States for Treatment of Non-Cirrhotic NASH with Moderate-to-Advanced Liver Fibrosis","authors":"Jesse Fishman,&nbsp;Yestle Kim,&nbsp;Michael R. Charlton,&nbsp;Zachary J. Smith,&nbsp;Tom O’Connell,&nbsp;Eric M. Bercaw","doi":"10.1007/s12325-024-02989-5","DOIUrl":"10.1007/s12325-024-02989-5","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;As of March 2024, resmetirom is the first and only therapy approved in the United States (US) for the treatment of adults with non-cirrhotic nonalcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis (MALF) consistent with stages F2/F3 fibrosis. Estimates of the diagnosed, treatment-eligible NASH population are poorly understood due to diagnostic variability. This study provides a contemporary estimate of the size of the US resmetirom treatment-eligible population.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;A dynamic population calculator was developed combining literature, screening guidelines, resmetirom study criteria, and analyses of the NHANES 2017–March 2020 cycle. It computes NASH prevalence, proportion non-cirrhotic NASH with MALF, Year 1 diagnosis, and new diagnoses in Years 2 and 3. NASH prevalence was estimated by applying the American Association of Clinical Endocrinology screening algorithm and recommended NIT cut-offs in the NHANES dataset. The proportion of non-cirrhotic NASH with MALF was informed by analyses of the Forian US integrated medical claims database using NASH and cirrhosis-specific ICD-10-CM codes and FIB-4 scores. NASH diagnosis rates were obtained from published estimates and NHANES responses. Treatment-eligible population growth was projected using published incidence data. Estimates were compared to a NASH budget-impact-analysis (BIA) from the Institute for Clinical and Economic Review (ICER).&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;In the base case, a NASH prevalence of 4.6% was modeled (range 1.3–14.2%). This value was multiplied by the proportion estimated to have non-cirrhotic MALF (i.e., 35%). Published analyses suggest a diagnosis rate of ~ 10% (range 3.3–14.3%) and ~ 16% year-over-year growth in the treatment-eligible population. Assuming a 1-million commercial-member population, the resmetirom treatment-eligible population was estimated as 1255–1699 in Years 1–3 following approval. Sensitivity analyses were conducted and comparison to the ICER BIA was influenced by different diagnosis rates.&lt;/p&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Estimation of the treatment-eligible population for resmetirom depends importantly on NASH diagnosis rates, which are predicted to be &lt; 15% in the 3 years after drug approval.&lt;/p&gt;&lt;h3&gt;Plain Language Summary&lt;/h3&gt;&lt;p&gt;Nonalcoholic steatohepatitis (NASH) is an advanced form of nonalcoholic fatty liver disease. Previously there were no treatments for NASH in the United States (US), but as of March 2024, the US Food and Drug Administration (FDA) approved resmetirom (REZDIFFRA™), a once-daily, oral therapy, in conjunction with diet and exercise, under accelerated approval for the treatment of adults (aged 18 years or older) with non-cirrhotic NASH with moderate-to-advanced liver fibrosis (MALF), consistent with stages F2–F3. It is not well understood how many diagnosed patients with NASH would be eligible for treatment with resmetirom; thus, this study aimed to estimate the size of the US resm","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02989-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249095","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":"Efficacy and Safety of Iparomlimab, an Anti-PD-1 Antibody, in Patients with Advanced Solid Tumors: A Phase 1c Study","authors":"Jianping Xiong,&nbsp;Weiwei Ouyang,&nbsp;Mengxiang Yang,&nbsp;Zhenyuan Gao,&nbsp;Huan Zhou,&nbsp;Hanmei Lou,&nbsp;Yabing Guo,&nbsp;Zhongyuan Xu,&nbsp;Ling Zheng,&nbsp;Ying Liu,&nbsp;Zhongfeng Wang,&nbsp;Ping Sun,&nbsp;Huerxidan Niyazi,&nbsp;Jianhua Wang,&nbsp;Yan Chen,&nbsp;Baihui Zhang,&nbsp;Lingyan Li,&nbsp;Xiaoyan Kang,&nbsp;Weijian Guo","doi":"10.1007/s12325-024-02981-z","DOIUrl":"10.1007/s12325-024-02981-z","url":null,"abstract":"<div><h3>Introduction</h3><p>Iparomlimab (QL1604) is a humanized immunoglobulin G4 mAb against programmed cell death protein 1 (PD-1). Here, we report the preliminary efficacy, safety, pharmacokinetics, and immunogenicity of iparomlimab in patients with advanced solid tumors.</p><h3>Methods</h3><p>In this open-label, phase 1c study, patients with advanced or metastatic solid tumors, either failed or had no standard therapies available, were enrolled and received intravenous iparomlimab at 3 mg/kg once every 3 weeks. The primary efficacy endpoint was the objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</p><h3>Results</h3><p>Between July 20, 2020, and September 6, 2021, 71 patients were enrolled and received at least one dose of iparomlimab. The ORR was 9.9% (7/71) and disease control rate was 36.6% (26/71). Median duration of response of all responders was 10.7 months [95% confidence interval (CI), 1.4-not estimable]. Additionally, the median time to progression, progression-free survival, and overall survival were 1.4 months (95% CI, 1.4–2.8), 1.4 months (95% CI, 1.4–2.7), and 9.7 months (95% CI, 7.2–15.3), respectively. A total of 52 (73.2%) patients experienced treatment-related adverse events (TRAEs) (grade ≥ 3, 19.7%). The most common TRAE (≥ 10%) was anemia (18.3%). A total of 20 (28.2%) experienced immune-related adverse events (grade ≥ 3, 7.0%). TRAEs leading to discontinuation of study drug occurred in 4 (5.6%) patients, including immune-mediated myocarditis (2 patients), Guillain–Barré syndrome (1 patient), and diarrhea (1 patient).</p><h3>Conclusions</h3><p>Iparomlimab showed preliminary clinical activity and had a manageable safety profile in patients with advanced solid tumors. These results support further investigation of iparomlimab as monotherapy or in combination therapy in advanced solid tumors.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov identifier, NCT05801094. Retrospectively registered in 2023–03–24.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249117","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}