Clinical therapeutics最新文献

{"title":"Analysis of Clinical Characteristics and Risk Factors for Severe Influenza A and Influenza B in Children","authors":"Peng Li ,&nbsp;Chang-qing Li ,&nbsp;Na Chen ,&nbsp;Yu Jing ,&nbsp;Xue Zhang ,&nbsp;Rui-yang Sun ,&nbsp;Wan-yu Jia ,&nbsp;Shu-qin Fu ,&nbsp;Chun-lan Song","doi":"10.1016/j.clinthera.2024.11.016","DOIUrl":"10.1016/j.clinthera.2024.11.016","url":null,"abstract":"<div><h3>Purpose</h3><div>The goal of this study was to develop and validate an online dynamic nomogram system for early differential diagnosis of influenza A and B.</div></div><div><h3>Methods</h3><div>Patients with severe influenza A and B admitted to Henan Children's Hospital from January 2019 to January 2022 were used as the modeling group (n = 161), and patients admitted from January to September 2023 were used as the validation group (n = 52). Univariate logistic regression and multivariate logistic regression were used to identify the risk variables of severe influenza A and B in children in the modeling group. The selected variables were used to build the nomogram, and the C-index, decision curve analysis, calibration curves, and receiver operating characteristic curves were used to assess the differentiation, calibration of the models, and external validation of the above models with validation group data.</div></div><div><h3>Findings</h3><div>Fever for &gt;3 days, vomiting, lymphocyte count (LY), and duration from onset to hospitalization were independent factors for the identification of severe influenza A and B. We created a dynamic nomogram (<span><span>https://ertong.shinyapps.io/influenza/</span><svg><path></path></svg></span>) that can be accessed online. The C-index was 0.92. In the modeling group, the AUC of the prediction model was 0.92 (95% CI, 0.87–0.98), the calibration curve showed a good fit between the predicted probability and the actual probability, with high comparability, and the decision curve analysis showed that the nomogram model had significant clinical benefits. The application of this model in external verification predicts that the AUC of the verification group is 0.749 (95% CI, 0.61–0.88), and the validation results were in good agreement with reality.</div></div><div><h3>Implications</h3><div>Fever for &gt;3 days, vomiting, lymphocyte count, and duration from onset to hospitalization have an impact on the differentiation of severe influenza A from severe influenza B. The prediction value and clinical benefit of the nomogram model are satisfactory.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 123-127"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilization of Immune Checkpoint Inhibitors in Human Epidermal Growth Factor Receptor 2–Negative, Advanced Metastatic, or Unresectable Gastric Cancer Under All Combined Positive Score Grading: Evaluation of Efficacy Based on Individual Patient Data Reconstruction and Secondary Analyses","authors":"Ning Deng MSc ,&nbsp;Zhijing Yan MSc ,&nbsp;Shengpeng Wang PhD ,&nbsp;Menghuan Song PhD ,&nbsp;Hao Hu PhD","doi":"10.1016/j.clinthera.2024.11.014","DOIUrl":"10.1016/j.clinthera.2024.11.014","url":null,"abstract":"<div><h3>Purpose</h3><div>The efficacy of several novel combinations of anti-programmed cell death protein 1 or its ligand antibodies with chemotherapy, which have become the new standard first-line combination therapy with favorable outcomes, was still not certain in patients with different combined positive score (CPS) grades. This research aimed to evaluate the efficacy of immune checkpoint inhibitor immunotherapy or immunochemotherapy at different CPS grades, compared with chemotherapy.</div></div><div><h3>Methods</h3><div>Kaplan-Meier (KM) curve reconstruction was employed to assess the overall survival (OS) and progression-free survival (PFS) of patients with gastric cancer. The graphical reconstruction algorithm was used to estimate the time-to-event outcomes from Kaplan-Meier curves of the overall cohort or reported subgroups (depending on CPS). <em>KMSubtraction</em> was used to derive the unreported survival data by matching participants in the overall cohort and known subgroups.</div></div><div><h3>Findings</h3><div>This analysis included 5072 patients in 5 trials (CheckMate 649, KEYNOTE-859, ORIENT-16, KEYNOTE-062, and JAVELIN Gastric 100). Immunochemotherapy exhibited more effectiveness than chemotherapy in most cases. For the overall cohort, sintilimab + chemotherapy exhibited the best effect in OS (hazard ratio [HR], 0.65; 95% CI, 0.55–0.76). Nivolumab + chemotherapy (HR, 0.75; 95% CI, 0.67–0.84), sintilimab + chemotherapy (HR, 0.52; 95% CI, 0.41–0.65), and pembrolizumab + chemotherapy (HR, 0.68; 95% CI, 0.58–0.81) exhibited favorable outcomes in OS in patients with a CPS ≥1, 5, and 10, respectively, and similarly in PFS. Avelumab + chemotherapy performed similarly to chemotherapy in OS but had poor PFS in the reported subgroup.</div></div><div><h3>Implications</h3><div>Finding suggests that immune checkpoint inhibitors combined with chemotherapy could enrich patients with benefits regardless of CPS grades, though subtle efficacy in low CPS subgroups. This study compared the efficacy of different immunotherapies combined with chemotherapy in patients with gastric cancer, but we acknowledge some differences between reconstructed and original data. Hopefully there will be more research investigating comparisons between current therapies rather than with chemotherapy only in the future.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 148-157"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kebilidi (eladocagene exuparvovec-tneq)","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.12.008","DOIUrl":"10.1016/j.clinthera.2024.12.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 176-177"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical Vancomycin Paste Over the Sternal Edge During Cardiac Surgery: Effects of Renal Function and Body Size on Systemic Exposure","authors":"Meng-Ta Tsai MD, PhD ,&nbsp;Yu-Ning Hu MD ,&nbsp;Jun-Neng Roan MD, PhD ,&nbsp;Chung-Dann Kan MD, PhD ,&nbsp;Yi-Chen Wang MD ,&nbsp;Chwan-Yau Luo MD, MS ,&nbsp;Chen-Hsi Chou PhD","doi":"10.1016/j.clinthera.2024.11.024","DOIUrl":"10.1016/j.clinthera.2024.11.024","url":null,"abstract":"<div><h3>Purpose</h3><div>Intraoperative topical vancomycin has been widely used in several surgical fields to prevent wound infection. However, there have been limited studies on the systemic exposure of topical vancomycin. The aim of this study was to investigate systemic exposure after topical vancomycin over the sternal edge in cardiac surgical patients. The impact of impaired renal function and body size on the exposure was also examined.</div></div><div><h3>Methods</h3><div>Topical vancomycin (2.5 g) was applied to the sternal edge in 129 adult cardiac surgical patients. Plasma concentrations were measured on postoperative days 0 through 7 and analyzed using linear mixed-effects models.</div></div><div><h3>Findings</h3><div>Sixty (46.5%) patients were in chronic kidney disease stages 3 to 5, including 20 patients in end-stage renal disease (ERSD) status with regular hemodialysis preoperatively. A total of 377 plasma vancomycin levels were modeled. It was reported that there was a 7.7% increase in vancomycin level per postoperative day for patients with ESRD in contrast to a decrease of 6.1% each day for patients without ESRD. Every increase of 1 mL/min/1.73 m² in the estimated glomerular filtration rate is associated with a 0.9% decline in vancomycin concentration. Increasing body surface area (BSA) by 0.1 m² reduces the vancomycin level by 6.3%. Model simulations using 10,000 replicates reported that the probability of vancomycin level &gt;10 mg/L declines to near 0 within 1 week after surgery in patients without ESRD, even in subjects with low estimated glomerular filtration rate and BSA. For the ESRD group with a BSA &lt;2 m², the chance of vancomycin &gt;10 mg/L is up to 20% to 30%.</div></div><div><h3>Implications</h3><div>Plasma exposure after topical vancomycin for the sternal edge is influenced by renal function and body size. The low probability of significant plasma vancomycin levels supports the typical fixed-dose strategy. For patients with ESRD receiving hemodialysis, accumulation of plasma vancomycin is worth cautioning.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 135-142"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Individualized Clinical Strategies for Polycystic Ovary Syndrome: Evidence From Clinical Trials and Emerging Pharmacotherapies","authors":"Murali Krishna Moka PhD ,&nbsp;Damal Kandadai Sriram FRCP ,&nbsp;Melvin George DM","doi":"10.1016/j.clinthera.2024.11.015","DOIUrl":"10.1016/j.clinthera.2024.11.015","url":null,"abstract":"<div><h3>Purpose</h3><div>Clinical trials are advancing the treatment of polycystic ovary syndrome (PCOS), an endocrine disorder affecting 8-13% of women. Lifestyle interventions, including nutritional plans, physical activity, and stress management, can improve reproductive hormones and metabolic health. Novel pharmacotherapies targeting hormonal, metabolic, and reproductive abnormalities are being explored for individualized treatment. Combination therapies and lifestyle interventions like acupuncture, high-intensity interval training, and vitamin D3 supplementation are also being explored.</div></div><div><h3>Methods</h3><div>We conducted a narrative review by searching English-language studies across electronic databases such as PubMed, Science direct, and Google Scholar for articles related to the topics of PCOS and novel drug therapies such as metformin, LIK-066, elagolix, saxenda, exenatide, clomiphene, letrozole, and other diagnostic interventions. Our review excluded preclinical studies and articles not in english.</div></div><div><h3>Findings</h3><div>In addition to pharmacological treatments, lifestyle interventions such as Tung's acupuncture, high-intensity interval training (HIIT), and vitamin D3 supplementation have proven effective in managing symptoms of PCOS and enhancing overall health outcomes. These interventions offer a complementary approach to traditional medical therapies, emphasizing the importance of integrating lifestyle modifications into the treatment plan for women with PCOS.</div></div><div><h3>Implications</h3><div>This comprehensive approach underscores the importance of tailored treatments in optimizing clinical outcomes and quality of life for women with PCOS. The aim of this review is to highlight recent advancements in the treatment of PCOS through clinical trials and emerging pharmacotherapies, emphasizing the need for individualized and multifaceted treatment approaches.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 158-167"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase I Study of the Pharmacokinetics and Safety of Ipatasertib, an Akt Inhibitor in Chinese Patients With Locally Advanced or Metastatic Solid Tumors","authors":"Jian Zhang ,&nbsp;Rujiao Liu ,&nbsp;Dhruvit Sutaria ,&nbsp;Rucha Sane ,&nbsp;Minhao Fan ,&nbsp;Rui Wang ,&nbsp;Grace Song ,&nbsp;Kui Chen ,&nbsp;Ksenia Arzumanova ,&nbsp;Xichun Hu","doi":"10.1016/j.clinthera.2024.11.021","DOIUrl":"10.1016/j.clinthera.2024.11.021","url":null,"abstract":"<div><h3>Purpose</h3><div>Ipatasertib is a selective inhibitor of Akt, a frequently activated protein kinase that plays a critical role in human cancers. The current clinical trial aimed to assess the pharmacokinetic properties, safety, and tolerability of ipatasertib administered to Chinese patients with locally advanced or metastatic solid tumors.</div></div><div><h3>Methods</h3><div>A Phase I, single-arm, open-label study was performed in Chinese patients with locally advanced or metastatic solid tumors for whom standard therapy either does not exist or has proven ineffective. Four hundred milligrams of ipatasertib was administered to patients as a single agent, starting with a single dose for 7 days and continuous daily dosing for 21 days, followed by 7 days off schedule. The pharmacokinetic properties of ipatasertib and its major metabolite M1 (GO37220) after single and multiple dose administration were assessed using a validated liquid chromatography–tandem mass spectrometry assay method. Safety was assessed throughout the study, and adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Tumor response was assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1.</div></div><div><h3>Findings</h3><div>Fourteen patients were enrolled, and all enrolled patients received at least 1 dose of the study treatment. Ipatasertib and M1 exposures were slightly higher than previously reported but comparable with exposures observed within the Asian population. Ipatasertib as a single agent demonstrated a manageable safety profile in Chinese patients, which is aligned with prior observation in global studies. Limited efficacy was observed in these patients with heavily pretreated diverse solid tumors.</div></div><div><h3>Implications</h3><div>This study of the pharmacokinetic properties, safety, and efficacy of ipatasertib in Chinese patients eventually contributed toward the development of Akt inhibitors in China. ClinicalTrials.gov identifier: NCT04341259.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 128-134"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of Risk Models for Predicting Febrile Neutropenia Among Breast Cancer Patients Receiving Chemotherapy: A Real-World Study","authors":"Shu-Wei Hsu MS ,&nbsp;Shao-Chin Chiang PharmD ,&nbsp;Jason C. Hsu PhD ,&nbsp;Yu Ko PhD","doi":"10.1016/j.clinthera.2024.11.011","DOIUrl":"10.1016/j.clinthera.2024.11.011","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer patients receiving chemotherapy may develop a serious complication called febrile neutropenia (FN). We aimed to validate and compare three existing FN prediction models for breast cancer patients receiving chemotherapy in Taiwan.</div></div><div><h3>Patients and methods</h3><div>This was a retrospective observational real-world study. Data were acquired from the clinical research databases of three study hospitals. Breast cancer patients who have received at least one antineoplastic chemotherapy drug were chosen for the analysis. For evaluating the occurrence of FN, we used both broad (a body temperature above 38°C with an absolute neutrophil count (ANC) below 0.5 × 10⁹/L or a body temperature above 38°C with a diagnosis of neutropenia) and narrow definitions (having both fever and neutropenia diagnoses or having both neutropenia and infection diagnoses). Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each selected FN model.</div></div><div><h3>Results</h3><div>Among the 1903 patients identified, when the broad and narrow definitions of FN were applied, 70 (3.7%) and 60 (3.2%) patients developed FN in the first cycle, respectively. Using the broad FN definition, Aagaard's model was the highest in sensitivity (90.0%), followed by Chantharakhit's (40.0%) and Chen's (7.2%); in specificity, Chen's (93.6%) was the highest. In addition, the accuracy was highest with the Chen model (90.4%). All three models’ PPVs were low, ranging from 0.5% to 4.2%, but all three models’ NPVs were over 96.3%. When the narrow FN definition was used, Chantharakhit's model showed a relatively high improvement in sensitivity (53.3%) and PPV (3.9%) while negligible increases or even slight decreases were seen in the other two models and in the other performance indicators of Chantharakhit's model.</div></div><div><h3>Conclusion</h3><div>The results of this study provide important information for clinicians when selecting models to identify patients at high-risk of FN. As the model performance observed was less than satisfactory, improving the prediction ability of the models is needed.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages e1-e4"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Prediction Model for Postoperative Nausea and Vomiting After Laparoscopic Surgery for Gynecologic Cancers","authors":"Yabin Zhu MMed ,&nbsp;Lin Jiang MMed ,&nbsp;Canlin Sun MMed ,&nbsp;Yunxiang Li MBBS ,&nbsp;Hong Xie MD","doi":"10.1016/j.clinthera.2024.11.018","DOIUrl":"10.1016/j.clinthera.2024.11.018","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative nausea and vomiting (PONV) is among the most common adverse events, accompanied with impaired prognosis. This study aimed to investigate independent predictors for PONV after laparoscopic surgery for gynecologic cancers and identify a nomogram model.</div></div><div><h3>Methods</h3><div>Elderly patients who underwent laparoscopic surgery for gynecologic cancers between 2021 and 2024 were retrospectively enrolled. The primary observational endpoint was set as the occurrence of PONV within 72 h after surgery. Independent risk factors associated with PONV were identified by binary logistic regression, and further incorporated into the nomogram prediction mode by R.</div></div><div><h3>Results</h3><div>Of 337 enrolled patients, 104 experienced PONV with an overall incidence of 30.9%. Multivariate logistic regression analysis indicated body mass index (BMI) ≥ 24.0 (OR: 2.67, 95% CI: 1.37–5.23, <em>P</em> = 0.004), Afpel score (OR: 6.54, 95% CI: 3.52–12.15, <em>P</em> &lt; 0.001), anxiety (OR: 3.14, 95% CI: 1.16–8.50, <em>P</em> = 0.025), 5-hydroxytryptamine (5-HT) (OR: 1.05, 95% CI: 1.02–1.07, <em>P</em> &lt; 0.001), prostaglandin E2 (PGE2) (OR: 1.05, 95% CI: 1.01–1.08, <em>P</em> = 0.007), and albumin/fibrinogen ratio (AFR) (OR: 0.40, 95% CI: 0.28–0.56, <em>P</em> &lt; 0.001) were six independent risk factors for PONV. The nomogram model based on these factors has good predictive value for PONV, with an AUC of 0.898.</div></div><div><h3>Conclusions</h3><div>This study identified an individual nomogram prediction model to visually represent the regression model for predicting PONV after laparoscopic surgery for gynecologic cancers.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages 143-147"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Tolerability of Home Infusions in Down Syndrome Regression Disorder","authors":"Jonathan D. Santoro MD ,&nbsp;Lina Nguyen RN ,&nbsp;Nicole A. Nishimori BS ,&nbsp;Ruby Ferris BS ,&nbsp;Benjamin N. Vogel BS ,&nbsp;Natalie K. Boyd BS ,&nbsp;Lilia Kazerooni BS ,&nbsp;Shermila Pia MD ,&nbsp;Mellad M. Khoshnood MD ,&nbsp;Saba Jafarpour MD","doi":"10.1016/j.clinthera.2024.11.023","DOIUrl":"10.1016/j.clinthera.2024.11.023","url":null,"abstract":"<div><h3>Purpose</h3><div>Down syndrome regression disorder (DSRD) is a rare neuropsychiatric condition affecting otherwise healthy individuals with Down syndrome. Multiple studies on DSRD have revealed that immunotherapy with intravenous immunoglobulin (IVIg) is both safe and effective, although site of infusion has never been studied. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD receiving home-based infusions.</div></div><div><h3>Methods</h3><div>A single-center, retrospective chart review evaluating infusion reactions was performed for individuals meeting criteria for DSRD and having received IVIg infusions between 2019 and 2024. Adverse events (AEs) were evaluated for severity and need for alterations in infusion plan. A cohort of individuals receiving home-based infusions was compared with a cohort of individuals receiving infusions at an academic medical center.</div></div><div><h3>Findings</h3><div>A total of 315 individuals (162 institutional infusions [51%] and 153 home infusions [49%]) met the inclusion criteria. There were no statistical differences between the demographic and clinical features of the cohorts. Individuals receiving home infusions had the same rate of AE during an infusion (<em>P</em> = 0.14), although they did have a lower number of total AEs (<em>P</em> &lt; 0.001). Individuals receiving home infusions experienced a lower number of behavioral issues with infusions (<em>P</em> = 0.03) and had significantly lower discontinuations of infusions secondary to behavioral issues (<em>P</em> = 0.04).</div></div><div><h3>Implications</h3><div>Rates of AEs and serious AEs in those with DSRD were the same regardless of site of infusion. These data should be considered in policy regarding the appropriateness of home-based infusions as a safe alternative, when suitable for patients and caregivers, for individuals with DSRD.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages e27-e33"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of Challenges and Opportunities in the Implementation of Managed Entry Agreements for Advanced Therapy Medicinal Products","authors":"Andrea Greco MSc ,&nbsp;Geert W.J. Frederix PhD ,&nbsp;Lotty Hooft PhD ,&nbsp;Renske M.T. Ten Ham PhD","doi":"10.1016/j.clinthera.2024.11.019","DOIUrl":"10.1016/j.clinthera.2024.11.019","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Managed Entry Agreements (MEAs) are agreements between firms and competent authorities for pricing and reimbursement, designed to enable coverage of new medicines while managing uncertainties around their financial impact or performance. Although these agreements can facilitate patient access, their complexity and costs seem to dampen enthusiasm for implementation. Nevertheless, MEAs remain a potential route, particularly for high-cost drugs with uncertain value claims. Given their pivotal role in bridging Advanced Therapy Medicinal Products (ATMPs) to patients, their foreseeable future implementation calls for a specific investigation of their associated challenges and opportunities. Therefore, this work aims to identify challenges and opportunities in implementing MEAs specifically for ATMPs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A systematic literature review was conducted on PubMed, MEDLINE, Scopus, and Google Scholar, based on the updated Preferred Reporting Items for Systematic Review and Meta-Analysis. This has been supplemented by a snowball search. Through the thematic content analysis, opportunities and challenges were identified and grouped into themes and subthemes. Afterward, the subgroup analysis was performed to investigate challenges and opportunities with outcome-based agreements (OBAs) versus financial-based agreements (FBAs), jurisdiction, and ATMP type.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Of the 787 peer-reviewed articles, 42 met the inclusion criteria. Challenges and opportunities were clustered into the mentioned themes: evidence generation and data management, financial and reimbursement, administration and resources, negotiation, and governance, law, and regulations. Of note, no specific challenges or opportunities were found to be cell- or gene-therapy-specific, but certain challenges seem amplified for ATMPs. Several differences emerged per MEA type and jurisdiction. OBAs are described to reward innovative and effective treatments and boost research and development (R&amp;D) returns. FBAs improve cost-effectiveness ratios but can negatively affect curative ATMP's revenues. Still, their versatility facilitates payer engagement in MEA combinations (eg, OBA with spread payments). The US decentralized health care system reported additional implementation challenges to OBAs. Each payer internally decides on reimbursement, and coordination among private payers is hindered by antitrust law. Yet, a new Cell and Gene Therapy Access model has been proposed. This would allow manufacturers to negotiate OBAs directly with the Centers for Medicare &amp; Medicaid Services avoiding individual negotiation with each state. In Europe, there is an evident interest in implementing spread payments, yet accounting rules currently hamper their implementation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implications&lt;/h3&gt;&lt;div&gt;This work offers insights into challenges and opportunities in MEAs implementation for ATMPs by investigating differenc","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 2","pages":"Pages e16-e26"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}