{"title":"临床试验中静脉lnp介导的mRNA治疗的不良反应:系统回顾和荟萃分析。","authors":"Wenhan Wu, Ziwei Wang","doi":"10.1080/17425247.2025.2517363","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Intravenous LNP-mediated mRNA therapy holds promise for treating various diseases, yet its safety, particularly regarding adverse events, remains a critical concern. This review systematically evaluates the adverse effects associated with this therapeutic approach.</p><p><strong>Methods: </strong>A comprehensive search of PubMed was conducted for clinical trials on intravenous LNP-mediated mRNA therapies. Data extraction focused on study design, participant demographics, and adverse events. Meta-analysis was performed to assess the incidence of treatment-emergent adverse events (TEAEs) and common manifestations. The risk of bias was assessed using the ROBINS-I tool.</p><p><strong>Results: </strong>A total of six phase 1/2 clinical trials on intravenous LNP-mediated mRNA therapies were included, with sample sizes ranging from 6 to 38 participants. The pooled incidence of TEAEs was 92.2% (95% CI: 77.7%-99.4%). Sensitivity analysis indicated that excluding one study with a single smaller dose reduced heterogeneity to 6.8%. The incidence of severe TEAEs was 9.2% (95% CI: 0%-38.1%) and showed substantial heterogeneity (I<sup>2</sup> = 89.87%), which was likely influenced by factors such as higher doses, multiple administrations, and patient-specific conditions like comorbidities.</p><p><strong>Conclusion: </strong>While low-dose, single-dose intravenous LNP-mediated mRNA therapies generally have a manageable safety profile, higher doses or repeated administrations may increase the risk of severe adverse events.</p><p><strong>Protocol registration: </strong>www.crd.york.ac.uk/prospero identifier is CRD42025643741.</p>","PeriodicalId":94004,"journal":{"name":"Expert opinion on drug delivery","volume":" ","pages":"1-9"},"PeriodicalIF":0.0000,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Adverse effects of intravenous LNP-mediated mRNA therapy in clinical trials: a systematic review and meta-analysis.\",\"authors\":\"Wenhan Wu, Ziwei Wang\",\"doi\":\"10.1080/17425247.2025.2517363\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Intravenous LNP-mediated mRNA therapy holds promise for treating various diseases, yet its safety, particularly regarding adverse events, remains a critical concern. This review systematically evaluates the adverse effects associated with this therapeutic approach.</p><p><strong>Methods: </strong>A comprehensive search of PubMed was conducted for clinical trials on intravenous LNP-mediated mRNA therapies. Data extraction focused on study design, participant demographics, and adverse events. Meta-analysis was performed to assess the incidence of treatment-emergent adverse events (TEAEs) and common manifestations. The risk of bias was assessed using the ROBINS-I tool.</p><p><strong>Results: </strong>A total of six phase 1/2 clinical trials on intravenous LNP-mediated mRNA therapies were included, with sample sizes ranging from 6 to 38 participants. The pooled incidence of TEAEs was 92.2% (95% CI: 77.7%-99.4%). Sensitivity analysis indicated that excluding one study with a single smaller dose reduced heterogeneity to 6.8%. The incidence of severe TEAEs was 9.2% (95% CI: 0%-38.1%) and showed substantial heterogeneity (I<sup>2</sup> = 89.87%), which was likely influenced by factors such as higher doses, multiple administrations, and patient-specific conditions like comorbidities.</p><p><strong>Conclusion: </strong>While low-dose, single-dose intravenous LNP-mediated mRNA therapies generally have a manageable safety profile, higher doses or repeated administrations may increase the risk of severe adverse events.</p><p><strong>Protocol registration: </strong>www.crd.york.ac.uk/prospero identifier is CRD42025643741.</p>\",\"PeriodicalId\":94004,\"journal\":{\"name\":\"Expert opinion on drug delivery\",\"volume\":\" \",\"pages\":\"1-9\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-06-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert opinion on drug delivery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/17425247.2025.2517363\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on drug delivery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17425247.2025.2517363","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Adverse effects of intravenous LNP-mediated mRNA therapy in clinical trials: a systematic review and meta-analysis.
Introduction: Intravenous LNP-mediated mRNA therapy holds promise for treating various diseases, yet its safety, particularly regarding adverse events, remains a critical concern. This review systematically evaluates the adverse effects associated with this therapeutic approach.
Methods: A comprehensive search of PubMed was conducted for clinical trials on intravenous LNP-mediated mRNA therapies. Data extraction focused on study design, participant demographics, and adverse events. Meta-analysis was performed to assess the incidence of treatment-emergent adverse events (TEAEs) and common manifestations. The risk of bias was assessed using the ROBINS-I tool.
Results: A total of six phase 1/2 clinical trials on intravenous LNP-mediated mRNA therapies were included, with sample sizes ranging from 6 to 38 participants. The pooled incidence of TEAEs was 92.2% (95% CI: 77.7%-99.4%). Sensitivity analysis indicated that excluding one study with a single smaller dose reduced heterogeneity to 6.8%. The incidence of severe TEAEs was 9.2% (95% CI: 0%-38.1%) and showed substantial heterogeneity (I2 = 89.87%), which was likely influenced by factors such as higher doses, multiple administrations, and patient-specific conditions like comorbidities.
Conclusion: While low-dose, single-dose intravenous LNP-mediated mRNA therapies generally have a manageable safety profile, higher doses or repeated administrations may increase the risk of severe adverse events.
Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42025643741.