Clinical therapeutics最新文献

{"title":"Thalidomide: Following Tragedy, a Repurposed Molecule With Continuing Opportunities for Clinical Benefit.","authors":"Paul Beninger","doi":"10.1016/j.clinthera.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.01.011","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413701","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":"The Effect of Intermittent Fasting Diet in Comparison With Low-Calorie Diet on Inflammation, Lipid Profile, Glycemic Index, Liver Fibrosis in Patients With Metabolic-Associated Fatty Liver Disease (MAFLD): A Randomized Controlled Trial.","authors":"Mehdi Karimi, Camellia Akhgarjand, Hirad Houjaghani, Maryam Mofidi Nejad, Amir Ali Sohrabpour, Hossein Poustchi, Hamed Mohammadi, Maryam Chamari, Hossein Imani","doi":"10.1016/j.clinthera.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.01.007","url":null,"abstract":"<p><strong>Background: </strong>Metabolic-associated fatty liver disease (MAFLD) is a prevalent condition with significant health and economic burdens. Dietary interventions, such as intermittent fasting (IF) and low-calorie diets (LCD), have shown promise in managing MAFLD, but their comparative efficacy remains unclear.</p><p><strong>Methods: </strong>This 10-month, parallel, single-blind randomized controlled trial compared the effects of a 16:8 IF diet with an LCD on 52 patients with MAFLD. Anthropometric, biochemical, liver enzyme, steatosis, fibrosis, inflammatory, and oxidative status parameters were assessed before and after the interventions.</p><p><strong>Results: </strong>Both diets led to improvements in anthropometric measures and liver enzyme levels, with no significant differences between groups. However, the LCD group showed superior outcomes in reducing liver steatosis (-52.40 vs -44.63 dB/m; P < 0.001) and fibrosis (-0.74 vs -0.004 Kpa; P = 0.01) compared to the IF group. LCD also led to a significant decrease in serum triglycerides (-24.08 vs 11.22 mg/dL; P = 0.02), while neither intervention significantly affected inflammatory markers or oxidative status.</p><p><strong>Conclusion: </strong>While both IF and LCD can be effective in managing MAFLD, LCD may offer additional benefits in terms of liver fat reduction and improvement in certain lipid parameters. These findings highlight the complexity of dietary interventions in MAFLD and the need for personalized approaches.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364212","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":"Hearing All Voices Through Patient-Focused Drug and Device Development Programs","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2025.01.004","DOIUrl":"10.1016/j.clinthera.2025.01.004","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages 179-180"},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364206","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":"Comparative safety of JAK inhibitors versus TNF or IL-17 inhibitors for cardiovascular disease and cancer in psoriatic arthritis and axial spondyloarthritis.","authors":"Sizheng Steven Zhao, David Riley, Gema Hernandez, Uazman Alam","doi":"10.1016/j.clinthera.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.01.005","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the risk of cardiovascular disease (CVD) and common solid cancers between JAK inhibitors (JAKi) versus TNF or IL-17 inhibitors, among people with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA).</p><p><strong>Methods: </strong>We used real-world electronic health records data from a predominantly North American population of PsA or axSpA. Initiators of JAKi (tofacitinib or upadacitinib) and TNFi were 1:1 propensity score matched. Cox models were used to compare time to CVD (acute myocardial infarction, stroke or revascularization) or common solid cancers (breast, colorectal, lung or prostate) over 3 years. Analyses were repeated for JAKi versus IL-17i. We performed sensitivity analyses with follow-up over 1 or 5 years, in those aged ≥65 years, or those initiating treatment before 2021.</p><p><strong>Results: </strong>The JAKi vs TNFi comparison included 2,200 matched individuals in each group over 3,092 and 4,618 person-years, respectively. Compared to TNFi, JAKi was not associated with higher risk of CVD (HR 0.977; 95% 0.632, 1.510) or cancer (HR 0.710; 0.462, 1.091) over 3 years' follow-up. JAKi vs IL-17i comparison included 2,287 individuals over 3,190 and 4,312 person-years, respectively. Compared to IL-17i, JAKi was not associated with risk of CVD (HR 1.114; 0.720,1.722) or cancer (HR 0.737; 0.484,1.122). Results across stratified analyses were directionally concordant.</p><p><strong>Conclusions: </strong>These results are reassuring that among a large population of people with PsA or axSpA, JAKi was not associated with increased risk of CVD or common solid cancers, compared to TNFi or IL-17i initiators. Ongoing monitoring of cardiovascular and cancer risks is needed.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364191","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":"Real-World Effectiveness of Sotrovimab in Ambulatory Patients With COVID-19: A Retrospective Cohort Study Using a Large Administrative Claims Database in the United States.","authors":"Christopher F Bell, Tasneem Lokhandwala, Daniel C Gibbons, Myriam Drysdale, Jane Wang, Emily J Lloyd","doi":"10.1016/j.clinthera.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.01.003","url":null,"abstract":"<p><strong>Purpose: </strong>To assess real-world effectiveness of sotrovimab for reducing severe clinical outcomes in patients with coronavirus disease 2019 (COVID-19) versus no treatment during the Delta/early Omicron variant periods.</p><p><strong>Methods: </strong>Patients diagnosed with COVID-19 between May 26, 2021, and April 5, 2022, were identified from US administrative claims data (Komodo Health). Cohorts included early treatment (sotrovimab, other monoclonal antibodies, or antivirals), prophylaxis monoclonal antibody treatment, and untreated for COVID-19. Patient characteristics and severe clinical outcomes (assessed in the 29-day post-treatment period, including hospitalization, mortality, ventilatory support/extracorporeal membrane oxygenation [ECMO], and hospital length of stay) were described for all cohorts, with comparative effectiveness analysis conducted among matched cohorts of sotrovimab-treated and untreated patients.</p><p><strong>Findings: </strong>In the descriptive analysis (N = 434,766 early treated; N = 2015 prophylaxis treated; N = 4,231,748 untreated), differences in age, comorbidity, and high-risk status were observed. Clinical outcomes occurred at low frequencies in all cohorts. In the effectiveness analysis (N = 34,160 sotrovimab treated; N = 68,320 untreated), treatment with sotrovimab significantly (P < 0.001 for all) reduced hospitalization (4.0% vs 4.7%), hospitalization and/or mortality (4.0% vs 5.2%), ventilatory support and/or ECMO (3.6% vs 6.5%), and length of inpatient stay (4.8 vs 6.2 days) versus no treatment. Stratification by age showed the significant reduction in the likelihood of 29-day all-cause hospitalization was only observed in patients aged >55 years, with greatest benefit observed among patients aged ≥65 years (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.49-0.63). Likelihood of all-cause hospitalization was lower among sotrovimab-treated versus untreated patients during the Delta (OR 0.66; 95% CI 0.57-0.76), Omicron BA.1 (OR 0.88; 95% CI 0.81-0.95), and BA.2 (OR 0.58; 95% CI 0.43-0.79) variant predominant periods.</p><p><strong>Implications: </strong>Sotrovimab was associated with a reduced risk of severe clinical outcomes in patients with COVID-19 at high risk of progression during the Delta and early Omicron (BA.1 and BA.2) variant periods.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254826","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":"Effects of Coenzyme Q10 Supplementation on Metabolic Indicators in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis","authors":"Yinshuang Li ,&nbsp;Amr Ali Mohamed Abdelgawwad El-Sehrawy ,&nbsp;Amar Shankar ,&nbsp;Manish Srivastava ,&nbsp;Jaafaru Sani Mohammed ,&nbsp;Ahmed Hjazi ,&nbsp;Mandeep Singh ,&nbsp;I.B. Sapaev ,&nbsp;Yasser Fakri Mustafa ,&nbsp;Munther Kadhim Abosaoda","doi":"10.1016/j.clinthera.2024.12.010","DOIUrl":"10.1016/j.clinthera.2024.12.010","url":null,"abstract":"<div><h3>Background</h3><div>Coenzyme Q10 (CoQ10) is a naturally occurring antioxidant that has been suggested to have beneficial effects on lipid profiles and blood pressure. This systematic review and meta-analysis aim to evaluate the effects of CoQ10 supplementation on these parameters in patients with Type 2 Diabetes (T2D).</div></div><div><h3>Objective</h3><div>To assess the impact of CoQ10 supplementation on lipid profiles and blood pressure in individuals diagnosed with Type 2 Diabetes.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted in databases such as PubMed, Cochrane Library, and Scopus for randomized controlled trials (RCTs) published up to July 2024. Studies included were those that examined the effects of CoQ10 supplementation on lipid profiles (total cholesterol, LDL, HDL, triglycerides) and blood pressure (systolic and diastolic) in T2D patients.</div></div><div><h3>Results</h3><div>16 studies were included. CoQ10supplementation reduced SBP (WMD: −3.86 mmHg, 95% CI: −6.01 to −1.71, <em>P</em> = 0.014, I² = 83.7%; <em>P</em> &lt; 0.001) and DBP (WMD: −2.70 mmHg, 95% CI: −4.50 to −0.91, <em>P</em> = 0.024, I² = 92.1%; <em>P</em> &lt; 0.001), but did not change lipid profile. Additionally, subgroup analysis indicated that the effects of CoQ10 on lipid profiles levels were more pronounced in studies where the daily dosage of CoQ10 was 100 mg or less, and the duration of the study was under 12 weeks.</div></div><div><h3>Conclusions</h3><div>Coenzyme Q10 supplementation appears to have a beneficial effect on lipid profiles and may contribute to lowering blood pressure in patients with Type 2 Diabetes. These findings suggest that CoQ10 could be a valuable adjunctive therapy for managing cardiovascular risk in this population. Additional in-depth research is needed to validate these findings and understand the underlying mechanisms in more detail.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages 235-243"},"PeriodicalIF":3.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187589","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":"Real-Life Efficacy and Safety of Glecaprevir/Pibrentasvir Pediatric Formulation for Chronic Hepatitis C Infection in Children Aged 3 to 12 Years: A Case Series of 6 Patients","authors":"Francesca Musto MD ,&nbsp;Marta Stracuzzi MD ,&nbsp;Alessandro Cibarelli MD ,&nbsp;Crescenzo Coppola MD ,&nbsp;Roberta Caiazzo MD ,&nbsp;Daniela David MD ,&nbsp;Raffaella Di Tonno MD ,&nbsp;Marc Lorenzo Garcia MD ,&nbsp;Maria Sole Valentino MD ,&nbsp;Vania Giacomet MD, PhD","doi":"10.1016/j.clinthera.2024.12.011","DOIUrl":"10.1016/j.clinthera.2024.12.011","url":null,"abstract":"<div><h3>Purpose</h3><div>Glecaprevir/pibrentasvir (GLE/PIB) has been approved by the European Medicines Agency and by US Food and Drug Administration for the treatment of children and adolescents aged 3 to 12 years with chronic hepatitis C (CHC) virus infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB pediatric formulations in children aged 3 to 12 years with CHC.</div></div><div><h3>Methods</h3><div>This case series describes a pediatric population (3 to ≤12 years of age) treated with a weight-based dose of GLE/PIB pediatric formulation once daily for 8 weeks. The effectiveness end point was a sustained virologic response 12 weeks after the end of treatment. Safety was assessed on adverse events and clinical/laboratory data.</div></div><div><h3>Findings</h3><div>Six patients (median age 6 years; interquartile range, 3 years) were enrolled and treated between March 2023 and December 2023. Genotype distribution was as follows: 4 of 6 genotype 1 (60%), 1 of 6 genotype 2 (20%), and 1 of 6 genotype 3 (20%). Median viral load at baseline was 541,000 IU/mL (interquartile range, 641,000 IU/mL). All (100%) patients completed treatment. Sustained virologic response (SVR) 12 weeks after the end of treatment was 100%. No virologic relapse or breakthrough was observed. No adverse events occurred.</div></div><div><h3>Implications</h3><div>This study confirmed the real-life effectiveness and safety profile of an 8-week treatment with GLE/PIB for CHC in children aged 3 to 12 years.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 3","pages":"Pages 244-247"},"PeriodicalIF":3.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187776","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":"Sex Differences in Response to a 12-Week Resistance Training Exercise Intervention After Cardiac Surgery: A Proof-of-Concept Intervention Trial.","authors":"Basmah Safdar, Angela F Jarman, Tracy E Madsen, Lauren E DeLamielleure, Bin Zhou, Robert Axtell, Arnar Geirsson, Abeel A Mangi","doi":"10.1016/j.clinthera.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.01.002","url":null,"abstract":"<p><strong>Purpose: </strong>Cardiopulmonary rehabilitation, which often follows major acute cardiac events, is traditionally focused on aerobic exercise and has been associated with decreased morbidity and mortality. Its benefit among cardiac surgery patients is less clear, as is the role of resistance-based exercise programs and their sex-specific effects. This study seeks to evaluate the safety and feasibility of a 12-week resistance training program in patients post cardiac surgery through a sex-specific lens.</p><p><strong>Methods: </strong>We conducted a nonrandomized feasibility trial with a 12-week strength training exercise intervention. The primary outcome was safety and feasibility. Secondary outcomes included changes in strength, endurance, and functional capacity; and sex differences among these. Adult participants post open-heart surgery who had completed traditional cardiac rehabilitation were consented. Both patients who completed (cases) or did not complete (controls) a tailored 12-week resistance training program underwent comprehensive assessment of physiologic and physical fitness measures pre- and postintervention.</p><p><strong>Findings: </strong>Nine participants enrolled in the trial, including 6 in the intervention arm (median age 61 years; 67% male) and 3 in the control arm (median age 66 years; 67% male). No serious adverse events were noted, indicating safety of the intervention. Participants completed a mean of 34.8/36 (96.7%) of sessions, indicating the feasibility of the program. Although not powered for statistical significance, patients experienced positive trends of improvement in measures of hand grip strength, endurance, and functional capacity with the intervention. When stratified, females experienced greater gains than males in these measures.</p><p><strong>Implications: </strong>This proof-of-concept study found that resistance-based exercise after cardiac surgery is well tolerated and feasible. Although all patients experienced improvements in exercise parameters, females reported greater relative improvement than males.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187781","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":"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}