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Efficacy and Safety of Iparomlimab, an Anti-PD-1 Antibody, in Patients with Advanced Solid Tumors: A Phase 1c Study 抗 PD-1 抗体 Iparomlimab 对晚期实体瘤患者的疗效和安全性:1c期研究
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-14 DOI: 10.1007/s12325-024-02981-z
Jianping Xiong, Weiwei Ouyang, Mengxiang Yang, Zhenyuan Gao, Huan Zhou, Hanmei Lou, Yabing Guo, Zhongyuan Xu, Ling Zheng, Ying Liu, Zhongfeng Wang, Ping Sun, Huerxidan Niyazi, Jianhua Wang, Yan Chen, Baihui Zhang, Lingyan Li, Xiaoyan Kang, Weijian Guo

Introduction

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.

Methods

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.

Results

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).

Conclusions

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.

Trial Registration

ClinicalTrials.gov identifier, NCT05801094. Retrospectively registered in 2023–03–24.

简介伊帕单抗(QL1604)是一种针对程序性细胞死亡蛋白1(PD-1)的人源化免疫球蛋白G4 mAb。方法在这项开放标签的1c期研究中,入组了晚期或转移性实体瘤患者,这些患者要么治疗失败,要么没有标准疗法可用,他们接受了静脉注射伊帕单抗,剂量为3 mg/kg,每3周一次。主要疗效终点是研究者根据实体瘤反应评价标准(RECIST)1.1版评估的客观反应率(ORR)。结果2020年7月20日至2021年9月6日期间,71名患者入组并接受了至少一次伊帕单抗治疗。ORR为9.9%(7/71),疾病控制率为36.6%(26/71)。所有应答者的中位应答持续时间为10.7个月[95%置信区间(CI),1.4-无法估计]。此外,中位进展时间、无进展生存期和总生存期分别为1.4个月(95% CI,1.4-2.8)、1.4个月(95% CI,1.4-2.7)和9.7个月(95% CI,7.2-15.3)。共有52名(73.2%)患者出现了治疗相关不良事件(TRAE)(≥3级,19.7%)。最常见的不良反应(≥10%)是贫血(18.3%)。共有 20 例(28.2%)出现免疫相关不良事件(≥ 3 级,7.0%)。导致停药的不良反应有4例(5.6%),包括免疫介导的心肌炎(2例)、格林-巴利综合征(1例)和腹泻(1例)。这些结果支持进一步研究iparomlimab在晚期实体瘤中作为单药或联合疗法的应用。追溯注册于 2023-03-24。
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引用次数: 0
Ten Recommendations for Accelerating Hypertension and Diabetes Control to Reduce Stroke, Heart, and Renal Disease with the Aim to Save Lives in Cameroon Through Partnerships and Collaborations 关于加快高血压和糖尿病控制以减少中风、心脏病和肾病的十项建议,目的是通过伙伴关系和合作挽救喀麦隆的生命
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-14 DOI: 10.1007/s12325-024-02960-4
Anastase Dzudie, Mesmin Dehayem, Liliane Mfeukeu Kuate, Marie Solange Ndom, Christian Ngongang Ouankou, Peter Vanes Ebasone, Armel Djomou Ngongang, Epie Njume, Felicite Kamdem, Simeon Pierre Choukem, Noël Emmanuel Essomba, Jerome Ateudjieu, Francois Kaze Folefack, Erika Nang Obada, Aristide Nono, Brice Kitio, Patrice Tchendjou, Friedrich Thienemann, Jerome Boombhi, Chris Nadege Nganou, Gloria Ashuntantang, Alain Patrick Menanga, Andre Pascal Kengne, Sylvie Ndongo Amougou, Appolinaire Tiam, Farida Haoua, Eugene Sobngwi, Jean Claude Mbanya

Hypertension and diabetes are currently the most common, treatable, and controllable cardiovascular and metabolic risk factors for stroke, heart, and renal diseases in Cameroon. Hypertension affects 30% of adults aged ≥ 20 years with 90% as uncontrolled cases, while type 2 diabetes affects 6% of the same population, with 70% remaining underdiagnosed. Despite publication of the first Roadmap on raised blood pressure by the World Heart Federation in 2015, the Pan African Society of Cardiology Roadmap in 2017, and the technical package for cardiovascular disease management in primary health care (WHO-HEARTS) in 2020, very little progress has been made in improving the diagnosis, treatment, and control of cardiovascular risk factors and diseases in Cameroon. The Cameroon Cardiac Society and a dozen Cameroon non-communicable diseases societies, national organizations from the community and the civil society, along with researchers and members of academia and the health sector, came together under the patronage of representatives of the government to propose new strategies to improve hypertension and diabetes control and save lives in Cameroon. Two simple and practical algorithms for the management of hypertension and diabetes were developed. The ten recommendations tailored to be efficiently implemented in our country were summarized under the acronym ‘A SMART VIEW’ (Awareness, Screening, Manufacture, Activity, Research, Task-shifting, HIV/AIDS, Insurance, Education, and WHO-HEARTS). It is our hope that all stakeholders will further collaborate to remove barriers and enhance facilitators to deploy the proposed actions and reduce the burden of uncontrolled hypertension and untreated diabetes in Cameroon.

高血压和糖尿病是目前喀麦隆最常见、可治疗和可控制的中风、心脏病和肾病的心血管和代谢风险因素。在年龄≥ 20 岁的成年人中,30%患有高血压,其中 90% 的患者病情未得到控制;在同一人群中,6%患有 2 型糖尿病,其中 70% 的患者诊断不足。尽管世界心脏联盟于 2015 年发布了第一份关于高血压的路线图,泛非心脏病学会于 2017 年发布了路线图,世界卫生组织于 2020 年发布了初级卫生保健中心血管疾病管理的技术包(WHO-HEARTS),但喀麦隆在改善心血管风险因素和疾病的诊断、治疗和控制方面进展甚微。在政府代表的赞助下,喀麦隆心脏病学会和十几个喀麦隆非传染性疾病学会、来自社区和民间社会的国家组织,以及学术界和卫生部门的研究人员和成员齐聚一堂,提出了改善喀麦隆高血压和糖尿病控制、挽救生命的新战略。为高血压和糖尿病的管理制定了两个简单实用的算法。为在我国有效实施而量身定制的十项建议被概括为 "A SMART VIEW"(认识、筛查、生产、活动、研究、任务转移、艾滋病毒/艾滋病、保险、教育和世界卫生组织--HEARTS)。我们希望,所有利益攸关方将进一步合作,消除障碍,加强促进因素,以部署拟议的行动,减轻喀麦隆未得到控制的高血压和未得到治疗的糖尿病的负担。
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引用次数: 0
The 3 Ds: Depression, Dysbiosis, and Clostridiodes difficile 3 Ds:抑郁症、菌群失调和艰难梭状芽孢杆菌
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-14 DOI: 10.1007/s12325-024-02972-0
Antoine Boustany, Paul Feuerstadt, Glenn Tillotson

This paper explores the intricate relationship between depression, gut dysbiosis, and Clostridioides difficile infections, collectively termed “The 3 Ds”. Depression is a widespread mental disorder increasing in prevalence. It is recognized for its societal burden and complex pathophysiology, encompassing genetic, environmental, and microbiome-related factors. The consequent increased use of antidepressants has led to growing concerns about their effects on the gut microbiome. Various classes of antidepressants and antipsychotics show antimicrobial activity, potentially leading to shifts in the gut microbiome and contributing to the development of dysbiosis. Dysbiosis, in turn, can predispose individuals to opportunistic infections like C. difficile, a significant healthcare concern due to its high recurrence rates and severe impact on patients' quality of life. Further, the link between antidepressant use and an increased risk of C. difficile infection (CDI) is explored and, finally, the emergence of live biotherapeutic products as novel treatment options for recurrent CDI is discussed.

本文探讨了抑郁症、肠道菌群失调和艰难梭菌感染(统称为 "3D")之间错综复杂的关系。抑郁症是一种广泛存在的精神疾病,发病率不断上升。它因其社会负担和复杂的病理生理学(包括遗传、环境和微生物相关因素)而被公认。随着抗抑郁药物使用的增加,人们越来越关注这些药物对肠道微生物组的影响。各种类型的抗抑郁药和抗精神病药具有抗菌活性,可能会导致肠道微生物群发生变化,并导致菌群失调。反过来,菌群失调又会使患者易患艰难梭菌等机会性感染,而艰难梭菌的高复发率和对患者生活质量的严重影响是医疗保健领域的一个重大问题。此外,还探讨了使用抗抑郁药与艰难梭菌感染(CDI)风险增加之间的联系,最后讨论了活生物治疗产品作为复发性艰难梭菌感染的新型治疗方案的出现。
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引用次数: 0
Efficacy and Safety of Alpha-2 Agonists in Autism Spectrum Disorder: A Systematic Review 阿尔法-2 受体激动剂对自闭症谱系障碍的疗效和安全性:系统回顾
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-13 DOI: 10.1007/s12325-024-02980-0
Alan D. Kaye, Abigail M. Green, Joseph Tremblay Claude II, Charles P. Daniel, Jada F. Cooley, Kelly R. Sala, Pooja Potharaju, Ross Rieger, Shilpadevi Patil, Shahab Ahmadzadeh, Sahar Shekoohi

Background

This analysis is a systematic literature review assessing efficacy and adverse effects of three alpha-2 agonists for the symptomatic management of autism spectrum disorder (ASD).

Methods

The present investigation involved an extensive systematic search for eligible studies in PubMed, Embase, Cochrane Library, and Google Scholar. Nine studies, collectively incorporating 226 patients, were assessed.

Results

The results demonstrated promising indications for use of alpha-2 agonists in the symptomatic management of autism spectrum disorders, including improvement of hyperactivity, impulsivity, attention deficit symptoms, irritability, and stereotypies in many of the participants studied.

Conclusion

The present investigation encourages physicians to consider treatment outcomes of clonidine, guanfacine, and lofexidine to determine the most effective management of ASD-related symptoms and to minimize adverse effects. However, our review cannot provide definitive treatment protocols related to various study limitations.

背景本分析报告是一篇系统性文献综述,评估了三种α-2激动剂用于自闭症谱系障碍(ASD)对症治疗的疗效和不良反应。结果研究结果表明,α-2 受体激动剂在自闭症谱系障碍的对症治疗中具有良好的适应症,包括改善许多受试者的多动、冲动、注意力缺陷症状、易激惹和刻板行为。结论本调查鼓励医生考虑氯尼定、胍法辛和洛非西定的治疗效果,以确定最有效的自闭症谱系障碍相关症状治疗方法,并最大限度地减少不良反应。然而,由于各种研究的局限性,我们的综述无法提供明确的治疗方案。
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引用次数: 0
Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02 根据入组 HER2 IHC 状态确定曲妥珠单抗德鲁司坦对 HER2 表达实体瘤的疗效:DESTINY-PanTumor02的事后分析
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-11 DOI: 10.1007/s12325-024-02975-x
Ana Oaknin, Jung-Yun Lee, Vicky Makker, Do-Youn Oh, Susana Banerjee, Antonio González-Martín, Kyung Hae Jung, Iwona Ługowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Soham Puvvada, Ann Smith, Funda Meric-Bernstam

Introduction

DESTINY-PanTumor02 (NCT04482309) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd) in pretreated patients with human epidermal growth factor receptor 2 (HER2)-expressing [immunohistochemistry (IHC) 3+/2+] solid tumors across seven cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. Subgroup analyses by HER2 status were previously reported by central HER2 IHC testing, determined at enrollment or confirmed retrospectively. Reflecting the testing methods available in clinical practice, most patients (n = 202; 75.7%) were enrolled based on local HER2 IHC testing. Here, we report outcomes by HER2 IHC status as determined by the local or central test results used for study enrollment.

Methods

This phase 2, open-label study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (IHC 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥ 1 systemic treatment or without alternative treatments. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival.

Results

In total, 111 (41.6%) and 151 (56.6%) patients were enrolled with IHC 3+ and IHC 2+ tumors, respectively. In patients with IHC 3+ tumors, investigator-assessed confirmed ORR was 51.4% [95% confidence interval (CI) 41.7, 61.0], and median DOR was 14.2 months (95% CI 10.3, 23.6). In patients with IHC 2+ tumors, investigator-assessed ORR was 26.5% (95% CI 19.6, 34.3), and median DOR was 9.8 months (95% CI 4.5, 12.6). Safety was consistent with the known profile of T-DXd.

Conclusion

In line with previously reported results, T-DXd demonstrated clinically meaningful benefit in patients with HER2-expressing tumors, with the greatest benefit in patients with IHC 3+ tumors. These data support the antitumor activity of T-DXd in HER2-expressing solid tumors, irrespective of whether patients are identified by local or central HER2 IHC testing.

导读:DESTINY-PanTumor02(NCT04482309)评估了曲妥珠单抗德鲁司坦(T-DXd)在人表皮生长因子受体2(HER2)表达[免疫组化(IHC)3+/2+]实体瘤预处理患者中的疗效和安全性,涉及七个组群:子宫内膜、宫颈、卵巢、膀胱、胆道、胰腺和其他。按 HER2 状态进行的亚组分析之前已通过中心 HER2 IHC 检测进行了报告,这些检测结果在入组时确定或通过回顾性分析确认。为了反映临床实践中可用的检测方法,大多数患者(n = 202;75.7%)是根据局部 HER2 IHC 检测入组的。方法这项2期开放标签研究评估了T-DXd(5.4 mg/kg,每3周1次)用于治疗HER2表达(经局部或中心检测为IHC 3+/2+)的局部晚期或转移性疾病,这些患者均接受过≥1次系统治疗或未接受替代治疗。主要终点是研究者评估确认的客观反应率(ORR)。次要终点包括安全性、反应持续时间(DOR)、无进展生存期(PFS)和总生存期。结果分别有111例(41.6%)和151例(56.6%)IHC 3+和IHC 2+肿瘤患者入组。在IHC 3+肿瘤患者中,研究者评估确认的ORR为51.4%[95%置信区间(CI)41.7, 61.0],中位DOR为14.2个月(95% CI 10.3, 23.6)。在 IHC 2+ 肿瘤患者中,研究者评估的 ORR 为 26.5%(95% CI 19.6,34.3),中位 DOR 为 9.8 个月(95% CI 4.5,12.6)。结论与之前报道的结果一致,T-DXd在HER2表达肿瘤患者中显示出有临床意义的获益,其中IHC 3+肿瘤患者获益最大。这些数据支持T-DXd在HER2表达实体瘤中的抗肿瘤活性,无论患者是通过局部还是中央HER2 IHC检测确定的。
{"title":"Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02","authors":"Ana Oaknin,&nbsp;Jung-Yun Lee,&nbsp;Vicky Makker,&nbsp;Do-Youn Oh,&nbsp;Susana Banerjee,&nbsp;Antonio González-Martín,&nbsp;Kyung Hae Jung,&nbsp;Iwona Ługowska,&nbsp;Luis Manso,&nbsp;Aránzazu Manzano,&nbsp;Bohuslav Melichar,&nbsp;Salvatore Siena,&nbsp;Daniil Stroyakovskiy,&nbsp;Anitra Fielding,&nbsp;Soham Puvvada,&nbsp;Ann Smith,&nbsp;Funda Meric-Bernstam","doi":"10.1007/s12325-024-02975-x","DOIUrl":"10.1007/s12325-024-02975-x","url":null,"abstract":"<div><h3>Introduction</h3><p>DESTINY-PanTumor02 (NCT04482309) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd) in pretreated patients with human epidermal growth factor receptor 2 (HER2)-expressing [immunohistochemistry (IHC) 3+/2+] solid tumors across seven cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. Subgroup analyses by HER2 status were previously reported by central HER2 IHC testing, determined at enrollment or confirmed retrospectively. Reflecting the testing methods available in clinical practice, most patients (<i>n</i> = 202; 75.7%) were enrolled based on local HER2 IHC testing. Here, we report outcomes by HER2 IHC status as determined by the local or central test results used for study enrollment.</p><h3>Methods</h3><p>This phase 2, open-label study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (IHC 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥ 1 systemic treatment or without alternative treatments. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival.</p><h3>Results</h3><p>In total, 111 (41.6%) and 151 (56.6%) patients were enrolled with IHC 3+ and IHC 2+ tumors, respectively. In patients with IHC 3+ tumors, investigator-assessed confirmed ORR was 51.4% [95% confidence interval (CI) 41.7, 61.0], and median DOR was 14.2 months (95% CI 10.3, 23.6). In patients with IHC 2+ tumors, investigator-assessed ORR was 26.5% (95% CI 19.6, 34.3), and median DOR was 9.8 months (95% CI 4.5, 12.6). Safety was consistent with the known profile of T-DXd.</p><h3>Conclusion</h3><p>In line with previously reported results, T-DXd demonstrated clinically meaningful benefit in patients with HER2-expressing tumors, with the greatest benefit in patients with IHC 3+ tumors. These data support the antitumor activity of T-DXd in HER2-expressing solid tumors, irrespective of whether patients are identified by local or central HER2 IHC testing.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"4125 - 4139"},"PeriodicalIF":3.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02975-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201086","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
Efficacy and Safety of Somapacitan Relative to Somatrogon and Lonapegsomatropin in Pediatric Growth Hormone Deficiency: Systematic Literature Review and Network Meta-analysis 索马帕西坦与索马特罗贡和长效生长激素相比对小儿生长激素缺乏症的疗效和安全性:系统文献综述和网络元分析
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-11 DOI: 10.1007/s12325-024-02966-y
Lasse de Fries Jensen, Vasileios Antavalis, Jan Odgaard-Jensen, Annachiara Rossi, Alberto Pietropoli, Michael Højby

Introduction

Since direct comparisons of long-acting growth hormones (LAGHs) are lacking, analyses were performed to indirectly compare the efficacy and safety of somapacitan versus somatrogon and lonapegsomatropin in children with growth hormone deficiency (GHD).

Methods

A systematic literature review (SLR) identified studies of once-weekly LAGHs for the treatment of pediatric GHD. Indirect comparisons (ICs) using a Bayesian hierarchical network meta-analysis and a random effects model were performed using daily growth hormone (GH) 0.034 mg/kg/day (base case) or 0.024–0.034 mg/kg/day (alternative analyses) as the common comparator to compare height outcomes to 52 weeks [annualized height velocity, height velocity standard deviation score (SDS), and height SDS]. Identified evidence did not allow IC of safety or longer-term efficacy outcomes so these were qualitatively described.

Results

The SLR identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only), and one lonapegsomatropin trial comparing the LAGH with daily GH in treatment-naïve pre-pubertal children for IC. ICs revealed no differences at 52 weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH, with respect to all growth outcomes considered in children with GHD. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily GH, with the exception of observed injection site pain for somatrogon.

Conclusion

No efficacy and safety differences were identified in comparisons of once weekly somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH. All treatments were generally well tolerated, with the exception of observed injection site pain for somatrogon.

导言由于缺乏对长效生长激素(LAGHs)的直接比较,因此我们进行了分析,以间接比较索马普坦与索马曲贡(somatrogon)和长效生长激素(lonapegsomatropin)对生长激素缺乏症(GHD)患儿的疗效和安全性。采用贝叶斯分层网络荟萃分析和随机效应模型进行了间接比较(IC),将每日生长激素(GH)0.034 mg/kg/天(基本情况)或0.024-0.034 mg/kg/天(替代分析)作为共同比较对象,比较52周的身高结果[年化身高速度、身高速度标准偏差评分(SDS)和身高标准偏差]。结果SLR确定了两项索马帕西坦试验、三项索马特罗贡试验(其中一项仅纳入替代分析)和一项长效索马托品试验,这些试验对青春期前未接受治疗的儿童进行了LAGH与每日GH的IC比较。IC试验显示,52周时,在GHD儿童的所有生长结果方面,索马帕西坦与索马曲贡、长佩格索马托品以及每日GH均无差异。除了观察到索马曲贡注射部位疼痛外,所有三种LAGHs都有持续疗效,耐受性普遍良好,疗效和安全性与每日GH相当。除观察到索马曲贡注射部位疼痛外,所有治疗方法的耐受性普遍良好。
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引用次数: 0
Modeling the Clinical and Economic Burden of Therapeutic Inertia in People with Type 2 Diabetes in Saudi Arabia 沙特阿拉伯 2 型糖尿病患者治疗惰性的临床和经济负担建模
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-11 DOI: 10.1007/s12325-024-02978-8
Mohammed Alluhidan, Abdulrahman Alturaiki, Hana Alabdulkarim, Nasser Aljehani, Essam A. Alghamdi, Fahad Alsabaan, Abdullah A. Alamri, Samuel J. P. Malkin, Barnaby Hunt, Abdulaziz Alhossan, Ahmed Al-Jedai

Introduction

Therapeutic inertia in type 2 diabetes, defined as a failure to intensify treatment despite poor glycemic control, can arise due to a variety of factors, despite evidence linking improved glycemic control with reductions in diabetes-related complications. The present study aimed to evaluate the health and economic burden of therapeutic inertia in people with type 2 diabetes in Saudi Arabia.

Methods

The IQVIA Core Diabetes Model (v.9.0) was used to evaluate outcomes. Baseline cohort characteristics were sourced from Saudi-specific data, with baseline glycated hemoglobin (HbA1c) tested at 8.0%, 9.0%, and 10.0%. Modeled subjects were brought to an HbA1c target of 7.0% immediately or after delays of 1–5 years across time horizons of 3–50 years. Outcomes were discounted annually at 3.0%. Costs were accounted from a societal perspective and expressed in 2023 Saudi Arabian Riyals (SAR).

Results

Immediate glycemic control was associated with improved or equal life expectancy and quality-adjusted life expectancy and cost savings in all scenarios compared with delays in achieving target HbA1c. Combined cost savings ranged from SAR 411 (EUR 102) per person with a baseline HbA1c of 8.0% versus a 1-year delay over a 3-year time horizon, to SAR 21,422 (EUR 5291) per person with a baseline HbA1c of 10.0% versus a 5-year delay over a 50-year time horizon. Discounted life expectancy and quality-adjusted life expectancy were projected to improve by up to 0.4 years and 0.5 quality-adjusted life years (QALYs), respectively, with immediate glycemic control.

Conclusion

Therapeutic inertia was associated with a substantial health and economic burden in Saudi Arabia. Interventions and initiatives that can help to reduce therapeutic inertia are likely to improve health outcomes and reduce healthcare expenditure.

导言 2 型糖尿病的治疗惰性是指尽管血糖控制不佳但仍不加强治疗,尽管有证据表明血糖控制的改善与糖尿病相关并发症的减少有关,但治疗惰性的产生可能是由多种因素造成的。本研究旨在评估治疗惰性对沙特阿拉伯 2 型糖尿病患者造成的健康和经济负担。方法采用 IQVIA 核心糖尿病模型(v.9.0)评估结果。基线队列特征来自沙特的特定数据,基线糖化血红蛋白 (HbA1c) 测试值分别为 8.0%、9.0% 和 10.0%。在 3-50 年的时间跨度内,模型受试者的 HbA1c 目标值会立即达到 7.0%,或在延迟 1-5 年后达到 7.0%。结果以每年 3.0% 的速度贴现。结果与延迟达到目标 HbA1c 相比,立即控制血糖与预期寿命和质量调整后预期寿命的改善或相等以及在所有情况下的成本节约相关。综合成本节约范围从基线 HbA1c 为 8.0% 与延迟 1 年、时间跨度为 3 年相比的每人 411 沙特里亚尔(102 欧元),到基线 HbA1c 为 10.0% 与延迟 5 年、时间跨度为 50 年相比的每人 21422 沙特里亚尔(5291 欧元)。如果立即控制血糖,预计折现预期寿命和质量调整预期寿命将分别提高 0.4 年和 0.5 个质量调整寿命年。有助于减少治疗惰性的干预措施和倡议可能会改善健康结果并减少医疗支出。
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引用次数: 0
Evaluation of Aluminum and Magnesium Absorption Following the Oral Administration of an Antacid Suspension Containing Magaldrate in Healthy Women Under Fed Conditions 评估健康女性在进食条件下口服含镁砂的抗酸剂悬浮液后对铝和镁的吸收。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-09 DOI: 10.1007/s12325-024-02969-9
Maria Juliana Burgos Castillo, Maria Juliana Cruz Palacios, Kamila Iorgatchof Xavier, Silvana Aparecida Calafatti Carandina, Isaac Arbeláez Quintero, Leandro do Prado Assunção

Introduction

Antacids are commonly used during pregnancy, and they are approved for the relief of symptoms of gastroesophageal reflux disease (GERD) during pregnancy. However, there are no reports of the quantification of the absorption of aluminum and magnesium in the antacid magaldrate in women. The aim of this study was to quantify the rate and magnitude of absorption of aluminum and magnesium in magaldrate.

Methods

An open-label, controlled, randomized, one-treatment study with a two-group design was conducted in healthy women in a fed state. The volunteers had a standard breakfast, and 30 min later, they were given a single-medication sachet containing 500 mg of sodium alginate, 267 mg of sodium bicarbonate, 800 mg of magaldrate, and 120 mg of simethicone (group A, n = 8) or no medication (group B, n = 2). Blood samples were obtained 36 h before and up to 12 h after antacid administration. The method used for quantification was inductively coupled plasma–mass spectrometry.

Results

There was no absorption of aluminum in any of the blood samples from the healthy volunteers who received the drug or in those from the control group. Magnesium was detected at normal concentrations.

Conclusion

These findings suggest that the use of this antacid is safe and without risk in healthy women, including pregnant women.

Clinical Trial Registration

Clinicaltrials.gov registration: NCT06367452.

简介:抗酸剂是孕期常用的药物,已被批准用于缓解孕期胃食管反流病(GERD)的症状。然而,目前还没有关于妇女对抗酸剂麦角酸盐中铝和镁的吸收进行量化的报道。本研究的目的是量化麦角酸盐中铝和镁的吸收率和吸收量:方法:在处于进食状态的健康女性中开展了一项采用两组设计的开放标签、对照、随机、单一治疗研究。志愿者先吃一顿标准早餐,30 分钟后给她们服用一袋含有 500 毫克海藻酸钠、267 毫克碳酸氢钠、800 毫克镁醛酸盐和 120 毫克西米替丁的单一药物(A 组,n = 8)或不服用药物(B 组,n = 2)。在服用抗酸剂前 36 小时和服用后 12 小时内采集血液样本。采用电感耦合等离子体质谱法进行定量:结果:接受药物治疗的健康志愿者和对照组的血液样本中都没有铝的吸收。镁的浓度正常:这些研究结果表明,这种抗酸剂对健康妇女(包括孕妇)是安全和无风险的:临床试验注册:Clinicaltrials.gov 注册:临床试验注册:Clinicaltrials.gov 注册:NCT06367452。
{"title":"Evaluation of Aluminum and Magnesium Absorption Following the Oral Administration of an Antacid Suspension Containing Magaldrate in Healthy Women Under Fed Conditions","authors":"Maria Juliana Burgos Castillo,&nbsp;Maria Juliana Cruz Palacios,&nbsp;Kamila Iorgatchof Xavier,&nbsp;Silvana Aparecida Calafatti Carandina,&nbsp;Isaac Arbeláez Quintero,&nbsp;Leandro do Prado Assunção","doi":"10.1007/s12325-024-02969-9","DOIUrl":"10.1007/s12325-024-02969-9","url":null,"abstract":"<div><h3>Introduction</h3><p>Antacids are commonly used during pregnancy, and they are approved for the relief of symptoms of gastroesophageal reflux disease (GERD) during pregnancy. However, there are no reports of the quantification of the absorption of aluminum and magnesium in the antacid magaldrate in women. The aim of this study was to quantify the rate and magnitude of absorption of aluminum and magnesium in magaldrate.</p><h3>Methods</h3><p>An open-label, controlled, randomized, one-treatment study with a two-group design was conducted in healthy women in a fed state. The volunteers had a standard breakfast, and 30 min later, they were given a single-medication sachet containing 500 mg of sodium alginate, 267 mg of sodium bicarbonate, 800 mg of magaldrate, and 120 mg of simethicone (group A, <i>n</i> = 8) or no medication (group B, <i>n</i> = 2). Blood samples were obtained 36 h before and up to 12 h after antacid administration. The method used for quantification was inductively coupled plasma–mass spectrometry.</p><h3>Results</h3><p>There was no absorption of aluminum in any of the blood samples from the healthy volunteers who received the drug or in those from the control group. Magnesium was detected at normal concentrations.</p><h3>Conclusion</h3><p>These findings suggest that the use of this antacid is safe and without risk in healthy women, including pregnant women.</p><h3>Clinical Trial Registration</h3><p>Clinicaltrials.gov registration: NCT06367452.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"4089 - 4097"},"PeriodicalIF":3.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02969-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153000","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
Striving for Stability in Patients with COPD: A New Way Forward? 力求慢性阻塞性肺病患者的病情稳定:前进的新方向?
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-09 DOI: 10.1007/s12325-024-02982-y
MeiLan K. Han, Lowie E. G. W. Vanfleteren, Stefanie Kolterer, Rianne Stacey, Dave Singh

This article summarises key themes from a symposium held during the recent European Respiratory Society congress, which took place in Vienna, Austria, 7–11 September 2024. The symposium was sponsored by GSK and entitled ‘Striving for disease stability in COPD: Giving patients more of their best days’. During the session, the speakers (MeiLan Han, Lowie Vanfleteren and Dave Singh) highlighted the specific challenges of chronic obstructive pulmonary disease (COPD), such as its unpredictable and unstable nature, with additional insights provided from patients with COPD in the form of video interviews. The faculty discussed whether treatment standards and goals should be more ambitious to provide all patients the stability and predictability they deserve and the opportunity to do more while living with COPD.

本文总结了近期于 2024 年 9 月 7-11 日在奥地利维也纳举行的欧洲呼吸学会大会期间召开的研讨会的主要议题。研讨会由葛兰素史克公司赞助,主题为 "努力实现慢性阻塞性肺疾病的病情稳定:让患者度过更多美好时光"。会议期间,发言人(韩美兰、Lowie Vanfleteren 和 Dave Singh)强调了慢性阻塞性肺疾病(COPD)所面临的特殊挑战,如其不可预知性和不稳定性,并通过视频访谈的形式提供了慢性阻塞性肺疾病患者的额外见解。教员们讨论了治疗标准和目标是否应该更加雄心勃勃,以便为所有患者提供应有的稳定性和可预测性,并让他们有机会在患有慢性阻塞性肺病的情况下做更多的事情。
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引用次数: 0
Improvement Across Dimensions of Disease with Lebrikizumab Use in Atopic Dermatitis: Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Monotherapy Trials (ADvocate1 and ADvocate2). 使用来曲珠单抗治疗特应性皮炎可改善各方面的疾病:两项 3 期随机、双盲、安慰剂对照单药试验(ADvocate1 和 ADvocate2)。
IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-09-09 DOI: 10.1007/s12325-024-02974-y
Eric Simpson, Pablo Fernández-Peñas, Marjolein de Bruin-Weller, Peter A Lio, Chia-Yu Chu, Khaled Ezzedine, Helena Agell, Marta Casillas, Yuxin Ding, Fan Emily Yang, Evangeline Pierce, Thomas Bieber

Introduction: Atopic dermatitis is a complex, chronic, inflammatory skin disease that requires long-term control of symptoms like itch and sleep loss and improvement in quality of life, in addition to reduction of clinical signs. Lebrikizumab is a selective interleukin-13 inhibitor approved in the European Union, United Kingdom, United Arab Emirates, Canada, and Japan for treatment of moderate-to-severe atopic dermatitis in adults and adolescents. Here, we assess the magnitude of changes across signs and symptoms of atopic dermatitis with lebrikizumab monotherapy over the 16-week induction period in two phase 3 studies, ADvocate1 and ADvocate2.

Methods: Eligible adults (aged ≥ 18 years) and adolescents (aged 12 to < 18 years and weighing ≥ 40 kg) with moderate-to-severe atopic dermatitis were randomized to receive either 250 mg of lebrikizumab or placebo subcutaneously every two weeks. Least squares mean percentage change from baseline through week 16 was compared between lebrikizumab and placebo using mixed model repeated measure analysis for the following endpoints: Eczema Area and Severity Index (EASI), Pruritus Numeric Rating Scale (NRS), Sleep-Loss Scale, Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI).

Results: In both trials, significant (P < 0.05) improvements were observed for lebrikizumab treatment compared with placebo at each 2-week timepoint for EASI, Pruritus NRS, Sleep-Loss Scale, and POEM, and at each 4-week timepoint for DLQI, through week 16. Statistically significant (P < 0.001) improvements were observed at 16 weeks for lebrikizumab treatment versus placebo in ADvocate1/ADvocate2 for EASI (71.9%/75.0% vs. 35.6%/43.3%), Pruritus NRS (53.3%/46.3% vs. 21.4%/18.0%), Sleep-Loss Scale (57.7%/55.6% vs. 23.9%/25.5%), POEM (54.4%/45.8% vs. 18.8%/16.9%), and DLQI (64.2%/60.5% vs. 28.5%/32.2%). Patient photos show improvements in skin appearance when disease measures improve.

Conclusions: Lebrikizumab monotherapy resulted in significant and fast improvements in multiple dimensions of disease (clinical signs, symptoms, and quality of life) over 16 weeks in patients with moderate-to-severe atopic dermatitis.

Trial registration: ClinicalTrials.gov identifiers, NCT04146363; NCT04178967.

简介:特应性皮炎是一种复杂的慢性炎症性皮肤病:特应性皮炎是一种复杂的慢性炎症性皮肤病,除了减轻临床症状外,还需要长期控制瘙痒和睡眠不足等症状,改善生活质量。来曲珠单抗是一种选择性白细胞介素-13抑制剂,已在欧盟、英国、阿联酋、加拿大和日本获得批准,用于治疗成人和青少年的中重度特应性皮炎。在此,我们评估了两项三期研究(ADvocate1 和 ADvocate2)中来布利珠单抗单药治疗特应性皮炎 16 周诱导期的体征和症状变化幅度:符合条件的成人(年龄≥ 18 岁)和青少年(年龄在 12 岁至 18 岁之间):在这两项试验中,Lebrikizumab 单药治疗的疗效显著(P来曲珠单抗单药治疗中重度特应性皮炎患者16周后,疾病的多个方面(临床症状、体征和生活质量)都得到了显著而快速的改善:试验注册:ClinicalTrials.gov标识符,NCT04146363;NCT04178967。
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引用次数: 0
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Advances in Therapy
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