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.
{"title":"Efficacy and Safety of Iparomlimab, an Anti-PD-1 Antibody, in Patients with Advanced Solid Tumors: A Phase 1c Study","authors":"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","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":"41 11","pages":"4153 - 4171"},"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}
Pub Date : 2024-09-14DOI: 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.
{"title":"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","authors":"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","doi":"10.1007/s12325-024-02960-4","DOIUrl":"10.1007/s12325-024-02960-4","url":null,"abstract":"<div><p>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’ (<u>A</u>wareness, <u>S</u>creening, <u>M</u>anufacture, <u>A</u>ctivity, <u>R</u>esearch, <u>T</u>ask-shifting, HI<u>V</u>/AIDS, <u>I</u>nsurance, <u>E</u>ducation, and <u>W</u>HO-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.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"3996 - 4007"},"PeriodicalIF":3.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02960-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249115","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}
Pub Date : 2024-09-14DOI: 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.
{"title":"The 3 Ds: Depression, Dysbiosis, and Clostridiodes difficile","authors":"Antoine Boustany, Paul Feuerstadt, Glenn Tillotson","doi":"10.1007/s12325-024-02972-0","DOIUrl":"10.1007/s12325-024-02972-0","url":null,"abstract":"<div><p>This paper explores the intricate relationship between depression, gut dysbiosis, and <i>Clostridioides difficile</i> 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 <i>C. difficile</i>, 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 <i>C. difficile</i> infection (CDI) is explored and, finally, the emergence of live biotherapeutic products as novel treatment options for recurrent CDI is discussed.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"3982 - 3995"},"PeriodicalIF":3.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02972-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249116","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}
Pub Date : 2024-09-13DOI: 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.
{"title":"Efficacy and Safety of Alpha-2 Agonists in Autism Spectrum Disorder: A Systematic Review","authors":"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","doi":"10.1007/s12325-024-02980-0","DOIUrl":"10.1007/s12325-024-02980-0","url":null,"abstract":"<div><h3>Background</h3><p>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).</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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.</p><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"4299 - 4311"},"PeriodicalIF":3.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201083","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}
Pub Date : 2024-09-11DOI: 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, 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","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}
Pub Date : 2024-09-11DOI: 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.
{"title":"Efficacy and Safety of Somapacitan Relative to Somatrogon and Lonapegsomatropin in Pediatric Growth Hormone Deficiency: Systematic Literature Review and Network Meta-analysis","authors":"Lasse de Fries Jensen, Vasileios Antavalis, Jan Odgaard-Jensen, Annachiara Rossi, Alberto Pietropoli, Michael Højby","doi":"10.1007/s12325-024-02966-y","DOIUrl":"10.1007/s12325-024-02966-y","url":null,"abstract":"<div><h3>Introduction</h3><p>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).</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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.</p><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"4098 - 4124"},"PeriodicalIF":3.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02966-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201085","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}
Pub Date : 2024-09-11DOI: 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.
{"title":"Modeling the Clinical and Economic Burden of Therapeutic Inertia in People with Type 2 Diabetes in Saudi Arabia","authors":"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","doi":"10.1007/s12325-024-02978-8","DOIUrl":"10.1007/s12325-024-02978-8","url":null,"abstract":"<div><h3>Introduction</h3><p>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.</p><h3>Methods</h3><p>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).</p><h3>Results</h3><p>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.</p><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"4140 - 4152"},"PeriodicalIF":3.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02978-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201084","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}
Pub Date : 2024-09-09DOI: 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.
{"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, Maria Juliana Cruz Palacios, Kamila Iorgatchof Xavier, Silvana Aparecida Calafatti Carandina, Isaac Arbeláez Quintero, 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}
Pub Date : 2024-09-09DOI: 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.
{"title":"Striving for Stability in Patients with COPD: A New Way Forward?","authors":"MeiLan K. Han, Lowie E. G. W. Vanfleteren, Stefanie Kolterer, Rianne Stacey, Dave Singh","doi":"10.1007/s12325-024-02982-y","DOIUrl":"10.1007/s12325-024-02982-y","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"41 11","pages":"3977 - 3981"},"PeriodicalIF":3.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-024-02982-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153002","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}
Pub Date : 2024-09-09DOI: 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.
{"title":"Improvement Across Dimensions of Disease with Lebrikizumab Use in Atopic Dermatitis: Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Monotherapy Trials (ADvocate1 and ADvocate2).","authors":"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","doi":"10.1007/s12325-024-02974-y","DOIUrl":"https://doi.org/10.1007/s12325-024-02974-y","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifiers, NCT04146363; NCT04178967.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153001","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}