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Quality of Life Evaluation in Patients with Follicular Cell Lymphoma: A Real-World Study in Europe and the United States 滤泡细胞淋巴瘤患者的生活质量评估:欧美真实世界研究》。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-08 DOI: 10.1007/s12325-024-02882-1
Patrick Connor Johnson, Abigail Bailey, Qiufei Ma, Neil Milloy, Emilia Biondi, Ruben G. W. Quek, Sarah Weatherby, Sophie Barlow

Introduction

Follicular lymphoma (FL) is an indolent subtype of non-Hodgkin's lymphoma (NHL), characterized by a long natural course of remissions/relapses. We aimed to evaluate real-world quality of life (QoL) in patients with FL, by line of therapy (LOT), and across countries.

Methods

Data were drawn from the Adelphi FL Disease Specific Programme™, a cross-sectional survey of physicians and their patients in Europe [France, Germany, Italy, Spain, the United Kingdom (UK)], and the United States (US) from June 2021 to January 2022. Patients provided demographics and patient-reported outcomes via the European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30). Bivariate analysis assessed QoL versus NHL, across LOT [first line (1L), second line (2L), third line or later (3L+)] and country.

Results

Patients (n = 401) had a mean [standard deviation (SD)] age of 66.0 (9.24) years, 58.1% were male, and 41.9%/22.9% were Ann Arbor stage III/IV. Patients with FL mean EORTC global health status (GHS)/QoL, nausea/vomiting, pain, dyspnea, appetite loss, and diarrhea scores were statistically significantly worse (p < 0.05) versus the NHL reference values. Mean (SD) GHS/QoL worsened from 1L [56.5 (22.21)] to 3L+ [50.4 (20.11)]. Physical and role functioning, fatigue, pain, dyspnea, and diarrhea scores also significantly worsened across later LOTs (p < 0.05). Across all functional domains, mean scores were significantly lower (p < 0.05) and almost all symptom scores (excluding diarrhea) were significantly higher (p < 0.05) for European versus US patients.

Conclusions

Patients with FL at later LOTs had significantly worse scores in most QoL aspects than earlier LOTs. European patients had significantly lower functioning and higher symptom burden than in the US. These real-world findings highlight the need for novel FL therapies that alleviate patient burden, positively impacting QoL.

简介滤泡性淋巴瘤(FL)是非霍奇金淋巴瘤(NHL)的一种隐匿性亚型,其特点是缓解/复发的自然病程较长。我们的目的是评估FL患者在现实世界中的生活质量(QoL),按治疗方案(LOT)和国家进行评估:数据来自阿德尔菲 FL 特定疾病计划(Adelphi FL Disease Specific Programme™),这是一项于 2021 年 6 月至 2022 年 1 月对欧洲(法国、德国、意大利、西班牙、英国)和美国的医生及其患者进行的横断面调查。患者通过欧洲癌症研究和治疗组织 QoL 问卷(EORTC QLQ-C30)提供人口统计数据和患者报告结果。双变量分析评估了QoL与NHL、LOT[一线(1L)、二线(2L)、三线或三线以上(3L+)]和国家的关系:患者(n = 401)的平均[标准差(SD)]年龄为 66.0 (9.24)岁,58.1%为男性,41.9%/22.9%为Ann Arbor III/IV期。FL患者的平均EORTC总体健康状况(GHS)/生活质量(QoL)、恶心/呕吐、疼痛、呼吸困难、食欲不振和腹泻评分在统计学上明显降低(P晚期 LOT 的 FL 患者在大多数 QoL 方面的得分明显低于早期 LOT 患者。与美国相比,欧洲患者的功能明显较低,症状负担较重。这些真实世界的研究结果凸显了对新型 FL 疗法的需求,这种疗法可减轻患者的负担,并对 QoL 产生积极影响。
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引用次数: 0
Usability of the SB11 Pre-filled Syringe (PFS) in Patients with Retinal Diseases SB11 预灌封注射器 (PFS) 在视网膜疾病患者中的可用性。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-08 DOI: 10.1007/s12325-024-02937-3
Yujin Lee, Dominik Zalewski, Piotr Oleksy, Edward Wylęgała, Michał Orski, Jiwon Lee, Sunji Kim

Introduction

SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis®; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO).

Methods

This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product.

Results

A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study.

Conclusions

This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease.

Trial Registration

ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12.

简介SB11 (Byooviz™; Samsung Bioepis Co., Ltd.)是一种针对血管内皮生长因子A的雷尼珠单抗(Lucentis®; Genentech, Inc.)生物仿制药,用于治疗视网膜疾病。SB11的预灌封注射器(PFS)表现形式提供了一种替代小瓶给药的给药方法,具有提高安全性和注射器制备效率的潜力。本研究旨在评估医护人员(HCPs)按照使用说明配制和给视网膜静脉闭塞(RVO)继发新生血管性老年黄斑变性(nAMD)或黄斑水肿患者注射 SB11 PFS 玻璃体内注射剂的能力:本研究是一项开放标签、单臂、单剂量临床研究,旨在评估 SB11 PFS 在 nAMD 或继发于 RVO 的黄斑水肿患者中的可用性。四名高级保健人员为 34 名患者配制并注射 0.5 毫克 SB11 PFS IVT。产品使用任务(共 12 项任务)的完成情况由独立观察员进行评估。安全性评估持续到注射研究产品后 7 天:共有 34 名患者注册并完成了研究。34名患者(100%)成功完成了全部12项任务,没有出现与使用相关的失败。大多数患者(32 人,94.1%)未出现不良事件(AEs),2 人(5.9%)出现了 3 次治疗突发不良事件(TEAEs),严重程度为轻度至中度。研究期间未报告严重或重度TEAE:这项研究表明,HCPs 能够通过静脉注射成功配制和使用 SB11 PFS。没有发现意外的安全性问题。SB11 PFS是视网膜疾病患者使用SB11进行治疗的一种很有前景的选择:试验注册:ClinicalTrials.gov 识别码 NCT06176963;EudraCT 编号 2021-003566-12。
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引用次数: 0
Impacts of X-linked Retinitis Pigmentosa and Patient Pathways in European Countries: Results from the Cross-sectional EXPLORE XLRP-1 Physician Survey 欧洲国家 X 连锁视网膜色素变性的影响和患者途径:横断面 EXPLORE XLRP-1 医生调查的结果。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-08 DOI: 10.1007/s12325-024-02935-5
Katalin Pungor, Jennifer Lee, Tom Denee, Yerkebulan Kambarov, Riikka Nissinen, Kevin Ampeh, Marco Pellegrini, Francesco Parmeggiani

Introduction

X-linked retinitis pigmentosa (XLRP) is a rare, incurable, vision-threatening, genetic disease. In this study, we aimed to reveal the real-world burden of this disease from the viewpoint of retina specialists and geneticists involved directly in XLRP care and to identify unique insights that may not otherwise be available through typical clinical studies or health economic research.

Methods

In this exploratory, cross-sectional study (EXPLORE XLRP-1), retina specialists (n = 20) and geneticists (n = 5) in France, Germany, Italy, Spain, and the UK provided anonymized insights on their experiences managing patients with XLRP (n = 80) via an online survey and 60-min telephone interview.

Results

Survey respondents reported that patient independence decreased over time, where 37% of patients were considered “completely autonomous” at diagnosis versus 23% at the last consultation. At their last visit, 45% of patients were active in the workforce; 67% (12/18) of “completely autonomous” patients had active working status compared with 13% (1/8) of “completely dependent” patients. The average time from onset of symptoms to diagnosis was 4 years and varied among countries. In 78% of patients, XLRP was confirmed by genetic testing, the rate of which varied among countries (range, 50–94%), taking up to 6 months to receive results. Specialists identified unmet needs in XLRP management including more standardized assessments of quality of life (QoL) as well as easier and earlier access to specialists, genetic testing, patient support programs, and effective treatment options.

Conclusions

The diagnosis, genetic testing, and management pathways among patients with XLRP can vary considerably. There is a need for more standardized diagnosis and management pathways, and QoL assessments, due to the major impact that XLRP has on patients’ lives.

简介X 连锁色素性视网膜炎(XLRP)是一种罕见的、无法治愈的、威胁视力的遗传性疾病。在这项研究中,我们旨在从直接参与 XLRP 治疗的视网膜专家和遗传学家的角度,揭示这种疾病在现实世界中的负担,并找出典型的临床研究或健康经济研究可能无法获得的独特见解:在这项探索性横断面研究(EXPLORE XLRP-1)中,法国、德国、意大利、西班牙和英国的视网膜专家(n = 20)和遗传学家(n = 5)通过在线调查和 60 分钟电话访谈,就他们管理 XLRP 患者(n = 80)的经验提供了匿名见解:调查对象称,随着时间的推移,患者的独立性有所下降,37%的患者在诊断时被认为 "完全自主",而在最后一次就诊时只有23%的患者被认为 "完全自主"。在最后一次就诊时,45%的患者积极参加工作;67%的 "完全自主 "患者(12/18)积极参加工作,而 "完全依赖 "患者仅为13%(1/8)。从出现症状到确诊的平均时间为 4 年,不同国家之间存在差异。78%的患者通过基因检测确诊了XLRP,检测率因国家而异(范围为50%-94%),最长需要6个月才能得到结果。专家们指出了XLRP管理中尚未满足的需求,包括对生活质量(QoL)进行更标准化的评估,以及更容易、更早地获得专家、基因检测、患者支持计划和有效的治疗方案:结论:XLRP 患者的诊断、基因检测和管理途径可能存在很大差异。结论:XLRP 患者的诊断、基因检测和管理途径可能存在很大差异。由于 XLRP 对患者的生活造成了重大影响,因此需要更加标准化的诊断和管理途径以及 QoL 评估。
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引用次数: 0
Effect of Hepatic Impairment on Trofinetide Exposures Using an In Silico Physiologically Based Pharmacokinetic Model 使用硅生理药代动力学模型分析肝功能损伤对曲菲内酯暴露量的影响
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-04 DOI: 10.1007/s12325-024-02926-6
Mona Darwish, Obinna N. Obianom, James M. Youakim, Inger Darling, Viera Lukacova, Heather Bradley

Introduction

Trofinetide is the first drug to be approved for the treatment of Rett syndrome. Hepatic impairment is not expected to affect the pharmacokinetic (PK) profile of trofinetide because of predominant renal excretion. This study was conducted to help understand the potential impact of any hepatic impairment on trofinetide PK.

Methods

This study used physiologically based PK modeling to estimate trofinetide exposure (maximum drug concentration and area under the concentration-time curve from time zero to infinity) in virtual patients with mild, moderate, and severe hepatic impairment (per Child-Pugh classification) compared with virtual healthy subjects following a 12 g oral trofinetide dose.

Results

In individual deterministic simulations for matched individuals and stochastic simulations at the population level (100 virtual individuals simulated per population), as anticipated, predicted plasma exposures were similar for healthy subjects and for patients with mild, moderate, and severe hepatic impairment. However, predicted blood concentration exposures slightly increased with increasing severity of hepatic impairment because of change in hematocrit levels.

Conclusion

This study indicates that hepatic impairment is not expected to have a clinically relevant effect on exposure to trofinetide.

Graphical Abstract

简介特罗非肽是首个获准用于治疗雷特综合征的药物。由于特罗非肽主要通过肾脏排泄,因此肝功能损害预计不会影响特罗非肽的药代动力学(PK)特征。本研究旨在帮助了解肝功能损害对特罗芬肽药代动力学的潜在影响:本研究采用基于生理学的 PK 模型来估算轻度、中度和重度肝功能损害(根据 Child-Pugh 分级)虚拟患者与虚拟健康受试者在口服 12 克特罗非肽后的特罗非肽暴露量(从零时到无穷大的最大药物浓度和浓度-时间曲线下面积):在对匹配个体进行的个体确定性模拟和群体水平的随机模拟(每个群体模拟 100 个虚拟个体)中,正如预期的那样,健康受试者与轻度、中度和重度肝功能损害患者的预测血浆暴露量相似。然而,由于血细胞比容水平的变化,预测的血药浓度暴露量随着肝功能损害严重程度的增加而略有增加:本研究表明,肝功能损害预计不会对特罗非肽的暴露量产生临床相关影响。
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引用次数: 0
Differential Adherence to Free and Single-Pill Combination of Rosuvastatin/Ezetimibe: Findings from a Real-World Analysis in Italy 瑞舒伐他汀/依折麦布免费和单药组合的不同依从性:意大利真实世界分析结果。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-04 DOI: 10.1007/s12325-024-02916-8
Leopoldo Perez de Isla, Evangelos Liberopoulos, Melania Dovizio, Chiara Veronesi, Luca Degli Esposti, Alberto Zambon

Introduction

Adherence to cardiovascular drug treatment can significantly benefit from a reduced pill burden, but data on this matter derived from real-life settings are currently scanty. This analysis assessed the possible changes in adherence in patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free multi-pill combination who switched to ROS/EZE as single-pill combination in the setting of real clinical practice in Italy.

Methods

A retrospective analysis was conducted on the administrative databases for a catchment area of about seven million health-assisted residents. Adults receiving ROS/EZE as a single-pill combination from January 2010 to June 2020 (followed up to 2021) were identified. The date of the first prescription of single-pill combination of ROS/EZE was considered as the index date. The analysis included the users of ROS/EZE as a free combination during the year before the index date. Baseline demographic and clinical characteristics were collected during the period of data availability prior to the index date. Adherence to therapy was evaluated as proportion of days covered (PDC), namely the percentage of days during which a patient had access to medication, in the 12-month interval preceding or following the index date (PDC < 25% non-adherence; PDC = 25–75% partial adherence; PDC > 75% adherence).

Results

A total of 1219 patients (61.1% male, aged 66.2 ± 10.4 years) were included. Cardiovascular comorbidities were found in 83.3% of them, diabetes in 26.4%, and a combination of both in 16.2%. Single-pill combination of ROS/EZE was associated with a higher proportion of adherent patients compared to free-pill combination (75.2% vs 51.8%, p < 0.001).

Conclusions

This real-world analysis suggested that switching from a regimen based on separate pills to one based on a single-pill combination resulted in improved adherence to ROS/EZE therapy.

导言:减轻药片负担可显著提高心血管药物治疗的依从性,但目前从现实生活中获得的相关数据还很少。这项分析评估了在意大利实际临床实践中,使用罗伐他汀和依折麦布(ROS/EZE)免费多药组合治疗的患者转为使用罗伐他汀和依折麦布(ROS/EZE)单药组合治疗后在依从性方面可能发生的变化:我们对一个拥有约 700 万保健辅助居民的集水区的行政数据库进行了回顾性分析。研究确定了 2010 年 1 月至 2020 年 6 月(随访至 2021 年)期间接受 ROS/EZE 单药组合治疗的成年人。首次开具 ROS/EZE 单药组合处方的日期被视为指标日期。分析对象包括指数日期前一年内使用 ROS/EZE 免费复方制剂的患者。基线人口统计学特征和临床特征是在指数日期之前的数据可用期间收集的。治疗依从性以覆盖天数比例(PDC)进行评估,即在指数日期前后的 12 个月间隔内,患者可获得药物治疗的天数比例(PDC 75% 依从性):共纳入 1219 名患者(61.1% 为男性,年龄为 66.2 ± 10.4 岁)。其中 83.3% 的患者合并有心血管疾病,26.4% 的患者合并有糖尿病,16.2% 的患者合并有这两种疾病。与自由丸联合用药相比,ROS/EZE 单丸联合用药的患者坚持用药的比例更高(75.2% vs 51.8%,p 结论:ROS/EZE 单丸联合用药的患者坚持用药的比例更高(75.2% vs 51.8%,p):这项真实世界分析表明,从基于单独药片的治疗方案转变为基于单药片组合的治疗方案可提高 ROS/EZE 治疗的依从性。
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引用次数: 0
Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort eGFR 快速或非快速下降的 CKD 患者的临床疗效:来自 DISCOVER CKD 回顾性队列的报告。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-03 DOI: 10.1007/s12325-024-02913-x
Hiddo Heerspink, Stephen Nolan, Juan-Jesus Carrero, Matthew Arnold, Roberto Pecoits-Filho, Juan José García Sánchez, Eric Wittbrodt, Claudia Cabrera, Carolyn S. P. Lam, Hungta Chen, Eiichiro Kanda, Mitja Lainscak, Carol Pollock, David C. Wheeler

Introduction

This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992).

Methods

Data (2008–2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m2 recorded 90–730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events—including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)—and all-cause hospitalization.

Results

Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between − 6.21 and − 6.86 mL/min/1.73 m2 in patients with rapid eGFR decline versus between − 0.11 and − 0.77 mL/min/1.73 m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01–0.05).

Conclusion

Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes.

Trial Registration

ClinicalTrials.gov identifier, NCT04034992.

简介这项分析利用DISCOVER CKD(ClinicalTrials.gov,NCT04034992)的回顾性数据,研究了慢性肾脏病(CKD)患者的基线特征和临床结局,以及快速或非快速估计肾小球滤过率(eGFR)下降的情况:从英国临床实践研究数据链(UK Clinical Practice Research Datalink)、美国 TriNetX、美国有限索赔和电子健康记录数据集(US Limited Claims and Electronic Health Record Dataset)以及日本医疗数据视野(Japan Medical Data Vision)中提取数据(2008-2020 年)。纳入的患者均为慢性肾脏病患者(两次连续的 eGFR 测量结果相隔 90-730 天)。eGFR快速下降的定义是指数发布后2年的年下降率> 4 mL/min/1.73 m2;eGFR非快速下降的定义是年下降率≤ 4 mL/min/1.73 m2。评估的临床结果包括全因死亡率、肾脏结果(肾衰竭[进展到CKD 5期]或eGFR下降>50%和单纯肾衰竭的复合风险)、心血管事件(包括主要不良心血管事件(MACE;非致死性心肌梗死/脑卒中和心血管死亡))和全因住院:在所有数据库中,804 237 名符合条件的患者中有 13.7% 出现了 eGFR 快速下降。eGFR快速下降患者的年平均eGFR下降幅度在-6.21至-6.86 mL/min/1.73 m2之间,而eGFR非快速下降患者的年平均eGFR下降幅度在-0.11至-0.77 mL/min/1.73 m2之间。eGFR 快速下降与合并症负担和药物处方增加有关。在所有数据库中,eGFR 快速下降的患者发生肾衰竭或 eGFR 下降>50% 的复合风险明显高于 eGFR 非快速下降的患者(P 结论:eGFR 快速下降的患者发生肾衰竭或 eGFR 下降>50% 的复合风险明显高于 eGFR 非快速下降的患者:了解与慢性肾功能衰竭患者 eGFR 快速下降相关的患者因素,有助于确定哪些患者可从积极的管理中获益,从而将不良后果的风险降至最低:试验注册:ClinicalTrials.gov标识符,NCT04034992。
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引用次数: 0
Cost Offset of Dapagliflozin in the US Medicare Population with Cardio-Kidney Metabolic Syndrome 达帕格列净在患有心肾代谢综合征的美国医疗保险人群中的成本抵消。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-03 DOI: 10.1007/s12325-024-02919-5
Raymond C. Chang, Ryan L. Miller, Katherine W. Kwon, Joanna C. Huang

Introduction

Cardiovascular-kidney-metabolic (CKM) syndrome is highly prevalent in the US Medicare population and is projected to increase further. Sodium-glucose co-transporter 2 inhibitors have indications in chronic kidney disease (CKD), heart failure (HF), and type 2 diabetes (T2D), providing protective efficacy across conditions within CKM syndrome. The objective of this study was to develop a model to extrapolate key outcomes observed in pivotal clinical trials to the US Medicare population, and to assess the potential direct cost offsets associated with dapagliflozin therapy.

Methods

All US 2022 Medicare beneficiaries (≥ 65 years of age) eligible to receive dapagliflozin were estimated according to drug label indication and Medicare enrollment and claims data. Incidence of key outcomes from the dapagliflozin clinical program were modelled over a 4-year time horizon based on patient-level data with CKD, HF, and T2D. Published cost data of relevant clinical outcomes were used to calculate direct medical care cost-offset associated with treatment with dapagliflozin.

Results

In a population of 13.1 million patients with CKM syndrome, treatment with dapagliflozin in addition to historical standard of care (hSoC) versus hSoC alone led to fewer incidents of HF-related events (hospitalization for HF, 613,545; urgent HF visit, 98,896), renal events (kidney failure, 285,041; ≥ 50% sustained decline in kidney function, 375,137), and 450,355 fewer deaths (of which 225,346 and 13,206 incidences of cardiovascular and renal death were avoided). In total this led to medical care cost offsets of $99.3 billion versus treatment with hSoC only (dapagliflozin plus hSoC, $310.3 billion; hSoC, $211.0 billion).

Conclusion

By extrapolating data from trials across multiple indications within CKM syndrome, this broader perspective shows that considerable medical care cost offsets may result through attenuated incidence of clinical events in CKD, T2D, and HF populations if treated with dapagliflozin in addition to hSoC over a 4-year time horizon.

Graphical abstract available for this article.

Graphical Abstract

导言:心血管-肾脏-代谢(CKM)综合征在美国医疗保险人群中发病率很高,而且预计还会进一步增加。钠-葡萄糖协同转运体 2 抑制剂适用于慢性肾脏病 (CKD)、心力衰竭 (HF) 和 2 型糖尿病 (T2D),在 CKM 综合征的各种病症中具有保护作用。本研究的目的是建立一个模型,将关键临床试验中观察到的主要结果推断到美国医疗保险人群中,并评估与达帕格列净治疗相关的潜在直接成本抵消:根据药物标签上的适应症以及医疗保险的注册和理赔数据,估算了所有符合达帕格列净治疗条件的美国 2022 名医疗保险受益人(年龄≥ 65 岁)。根据患有 CKD、HF 和 T2D 的患者水平数据,对 4 年时间跨度内达帕格列净临床项目主要结果的发生率进行建模。已公布的相关临床结果的成本数据被用来计算与达帕格列净治疗相关的直接医疗成本抵消:结果:在 13.结果表明:在 1,300,000 名 CKM 综合征患者中,在使用传统标准疗法 (hSoC) 的同时使用达帕格列净治疗与仅使用 hSoC 相比,可减少心房颤动相关事件的发生(因心房颤动住院,613,545 人次;因心房颤动急诊,98,845 人次);肾衰竭,285,041 例;肾功能持续下降≥ 50%,375,137 例),死亡人数减少 450,355 例(其中避免了 225,346 例心血管死亡和 13,206 例肾脏死亡)。与仅使用 hSoC 相比,总计可抵消医疗成本 993 亿美元(达帕利氟嗪加 hSoC,3103 亿美元;hSoC,2110 亿美元):通过对 CKM 综合征中多个适应症的试验数据进行推断,这一更广阔的视角表明,在 4 年的时间跨度内,如果在使用 hSoC 的同时使用达帕格列净治疗 CKD、T2D 和 HF 患者,由于临床事件的发生率降低,可能会产生可观的医疗成本补偿。本文有图表摘要。
{"title":"Cost Offset of Dapagliflozin in the US Medicare Population with Cardio-Kidney Metabolic Syndrome","authors":"Raymond C. Chang,&nbsp;Ryan L. Miller,&nbsp;Katherine W. Kwon,&nbsp;Joanna C. Huang","doi":"10.1007/s12325-024-02919-5","DOIUrl":"10.1007/s12325-024-02919-5","url":null,"abstract":"<div><h3>Introduction</h3><p>Cardiovascular-kidney-metabolic (CKM) syndrome is highly prevalent in the US Medicare population and is projected to increase further. Sodium-glucose co-transporter 2 inhibitors have indications in chronic kidney disease (CKD), heart failure (HF), and type 2 diabetes (T2D), providing protective efficacy across conditions within CKM syndrome. The objective of this study was to develop a model to extrapolate key outcomes observed in pivotal clinical trials to the US Medicare population, and to assess the potential direct cost offsets associated with dapagliflozin therapy.</p><h3>Methods</h3><p>All US 2022 Medicare beneficiaries (≥ 65 years of age) eligible to receive dapagliflozin were estimated according to drug label indication and Medicare enrollment and claims data. Incidence of key outcomes from the dapagliflozin clinical program were modelled over a 4-year time horizon based on patient-level data with CKD, HF, and T2D. Published cost data of relevant clinical outcomes were used to calculate direct medical care cost-offset associated with treatment with dapagliflozin.</p><h3>Results</h3><p>In a population of 13.1 million patients with CKM syndrome, treatment with dapagliflozin in addition to historical standard of care (hSoC) versus hSoC alone led to fewer incidents of HF-related events (hospitalization for HF, 613,545; urgent HF visit, 98,896), renal events (kidney failure, 285,041; ≥ 50% sustained decline in kidney function, 375,137), and 450,355 fewer deaths (of which 225,346 and 13,206 incidences of cardiovascular and renal death were avoided). In total this led to medical care cost offsets of $99.3 billion versus treatment with hSoC only (dapagliflozin plus hSoC, $310.3 billion; hSoC, $211.0 billion).</p><h3>Conclusion</h3><p>By extrapolating data from trials across multiple indications within CKM syndrome, this broader perspective shows that considerable medical care cost offsets may result through attenuated incidence of clinical events in CKD, T2D, and HF populations if treated with dapagliflozin in addition to hSoC over a 4-year time horizon.</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":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490525","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}
引用次数: 0
Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy 曾接受奥希替尼和铂类化疗的转移性或不可切除的表皮生长因子受体突变非小细胞肺癌患者的实际治疗模式和临床疗效。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-03 DOI: 10.1007/s12325-024-02936-4
Jyoti Patel, Jie Meng, Hoa Le, Yoko Tanaka, Sudarshan Phani, Maribel Salas, Chuntao Wu, David Sternberg, Stephen Esker, Jeffrey P. Anderson, Aaron Crowley, Summera Q. Zhou, Camryn Lieb, Haiyan Sun, Quan V. Doan, Anu Santhanagopal, Karen L. Reckamp

Introduction

For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3‑DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population.

Methods

This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart).

Results

In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%.

Conclusion

The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

简介:表皮生长因子受体突变(EGFRm)局部晚期/转移性非小细胞肺癌(mNSCLC)患者在接受奥希替尼和铂类化疗(PBC)后病情出现进展,目前尚无统一的公认治疗标准。此外,标准疗法的疗效有限,表明医疗需求尚未得到满足,目前正在进行的临床研究正在解决这一问题,包括帕妥珠单抗德鲁司康(HER3-DXd)的 HERTHENA-Lung01 (NCT04619004)研究。然而,由于有关此类患者实际临床结果的信息有限,研究性疗法的早期试验缺乏足够的比较背景。本研究描述了EGFRm mNSCLC患者在既往接受过奥希替尼和PBC治疗后开始接受新疗法的真实世界临床特征、治疗和预后,包括与HERTHENA-Lung01人群相匹配的子集:这项回顾性分析使用了美国的一个数据库,该数据库来源于去标识化的电子健康记录。参考队列包括在2015年11月13日至2021年6月30日期间开始接受新疗法的表皮生长因子受体mNSCLC患者,这些患者之前曾接受过奥希替尼和PBC治疗。然后从参考队列中抽取与HERTHENA-Lung01人群相似的患者子集;使用倾向评分(PS)加权法对该匹配子集进行优化。终点为实际总生存期(rwOS)和实际无进展生存期(rwPFS)。对于有反应价值的患者亚组(间隔≥28天进行2次反应评估),计算确认的真实世界客观反应率(rwORR;≥28天后确认的部分/完全反应):在参考队列(N = 273)中,使用了多种治疗方案,但没有一种方案占主导地位。中位rwPFS和rwOS分别为3.3个月和8.6个月;确认的rwORR(可评估反应,n = 123)为13.0%。在匹配子集中(n = 126),经过 PS 加权后,中位 rwPFS 和 rwOS 分别为 4.2 个月和 9.1 个月;确证 rwORR(可评估反应,n = 57)为 14.1%:结论:EGFRm mNSCLC 患者中接受过大量预处理的人群的治疗情况较为分散,没有公认的统一治疗标准。对于能显著改善临床疗效的治疗方案,仍有大量需求未得到满足。
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引用次数: 0
Eteplirsen Treatment for Duchenne Muscular Dystrophy: A Qualitative Patient Experience Study 依替普利森治疗杜兴氏肌肉萎缩症:患者体验定性研究。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-03 DOI: 10.1007/s12325-024-02915-9
Joel Iff, Chloe Carmichael, Stephanie McKee, Ihor Sehinovych, Carolyn McNeill, Carolina Tesi-Rocha, Erik Henricson, Francesco Muntoni, Helen Kitchen

Introduction

Duchenne muscular dystrophy (DMD) is characterized by rapid functional decline. Current available treatment options aim to delay disease progression or stabilize physical function. To aid in healthcare providers’ understanding of the symptoms of disease that impact patients’ experience, this study explored children’s physical functioning, activities of daily living (ADLs), and health-related quality of life (HRQoL) after receiving eteplirsen, a weekly infusion indicated for individuals with DMD with exon 51 skip-amenable mutations.

Methods

Fifteen caregivers of male individuals with DMD participated in a 60-min, semi-structured interview. Open-ended questioning explored changes in the children’s condition or maintenance in abilities since eteplirsen initiation.

Results

Children with DMD (age 7–15 years [mean 10.9]; steroid treatment at interview, n = 8; time since eteplirsen initiation 3–24 months [mean 14.9]) were described by caregivers as ambulatory (n = 9) and non-ambulatory (n = 6). Caregivers of ambulatory children reported improvements or maintenance of walking ability (n = 7/9), running (n = 6/9), and using stairs (n = 4/9). Continued decline in using stairs was reported by two caregivers. In upper-limb functioning, improvements or maintenances in fine-motor movements were reported by nearly half of all caregivers (n = 7/15), with one caregiver noting a continued decline. Subsequent improvements or maintenances in ADLs were described. Improvements or maintenances in fatigue (n = 9/15), muscle weakness (n = 7/15), and pain (n = 6/15) were reported, although some caregivers described a continued decline (n = 3/15 fatigue, n = 1/15 muscle weakness, n = 2/15 pain). Importantly, most caregivers who reported maintenances in ability perceived this as a positive outcome (n = 6/9).

Conclusion

This exploratory study indicated that most caregivers perceived improvements or maintenances in aspects of their child’s physical functioning, ADLs, and HRQoL since eteplirsen initiation, which they perceived to be a positive outcome.

简介杜兴氏肌营养不良症(DMD)的特点是功能迅速衰退。目前可用的治疗方案旨在延缓疾病进展或稳定身体功能。为了帮助医疗服务提供者了解影响患者体验的疾病症状,本研究探讨了儿童在接受依替普森治疗后的身体功能、日常生活活动(ADLs)和健康相关生活质量(HRQoL):15 名男性 DMD 患者的护理人员参加了 60 分钟的半结构式访谈。开放式提问探讨了自开始使用依替匹森以来儿童病情的变化或能力的维持情况:DMD患儿(年龄7-15岁[平均10.9岁];接受访谈时接受类固醇治疗的患儿为8人;开始使用依替普仑生的时间为3-24个月[平均14.9个月])的护理人员将其描述为可活动的患儿(9人)和不可活动的患儿(6人)。不活动儿童的护理人员报告称,步行能力(7/9)、跑步能力(6/9)和走楼梯能力(4/9)均有所改善或保持不变。有两名看护人表示,走楼梯的能力继续下降。在上肢功能方面,近一半的照护者(n=7/15)表示精细运动能力有所改善或得到维持,只有一名照护者表示功能继续下降。据介绍,患者的日常活动能力随后得到改善或维持。据报告,疲劳(n = 9/15)、肌肉无力(n = 7/15)和疼痛(n = 6/15)均有所改善或维持,但也有一些护理人员表示持续下降(n = 3/15疲劳,n = 1/15肌肉无力,n = 2/15疼痛)。重要的是,大多数报告能力保持不变的护理人员认为这是一个积极的结果(n = 6/9):这项探索性研究表明,自开始使用依替匹森以来,大多数护理人员认为患儿的身体机能、ADL和HRQoL得到了改善或维持,他们认为这是一个积极的结果。
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引用次数: 0
A Response to: Letter to the Editor Regarding “Cardiovascular Insights for the Appropriate Management of Chronic Venous Disease: A Narrative Review of Implications for the Use of Venoactive Drugs” 回应:致编辑的信,关于 "心血管对慢性静脉疾病适当管理的启示:静脉活性药物使用影响的叙述性综述 "的来信。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-03 DOI: 10.1007/s12325-024-02934-6
Sergio Gianesini
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引用次数: 0
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Advances in Therapy
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