Endry H T Lim, Diederik van de Beek, Sanne de Bruin, Simon Rückinger, Claus Thielert, Renfeng Guo, Bruce P Burnett, Matthijs C Brouwer, Robert Zerbib, Camilla Chong, Niels C Riedemann, Alexander P Vlaar
{"title":"维洛莫单抗在危重有创机械通气COVID-19患者中的疗效和安全性的区域比较","authors":"Endry H T Lim, Diederik van de Beek, Sanne de Bruin, Simon Rückinger, Claus Thielert, Renfeng Guo, Bruce P Burnett, Matthijs C Brouwer, Robert Zerbib, Camilla Chong, Niels C Riedemann, Alexander P Vlaar","doi":"10.1136/bmjresp-2023-002206","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Vilobelimab, a first in class C5a-specific monoclonal antibody, improved 28-day and 60-day mortality in intubated COVID-19 patients in PANAMO, a phase 3 randomised, double-blind, placebo-controlled multicentre study. All-cause mortality was pre-specified to be analysed pooling by region (western Europe, South America, South Africa/Russia).</p><p><strong>Methods: </strong>Critically ill, invasively mechanically ventilated COVID-19 patients were randomised in a 1:1 ratio within 48 hours of intubation to receive vilobelimab treatment (six, 800 mg intravenous infusions) or placebo on top of standard of care. We analysed the efficacy and safety of vilobelimab based on prespecified geographic regions.</p><p><strong>Results: </strong>368 patients were randomised and analysed: 177 in the vilobelimab group and 191 in the placebo group. In western Europe (n=209), 28-day all-cause mortality was significantly lower in the vilobelimab group (21%) compared with placebo (37%) (HR 0.51 (95% CI: 0.30, 0.87), p=0.014). In South America (n=126), mortality was similar between groups (40% vs 37%; HR 0.94 (95% CI: 0.53, 1.67), p=0.83). In South Africa/Russia (n=33), mortality was 69% in the vilobelimab group and 87% in the placebo group (HR 0.62 (95% CI: 0.28, 1.38), p=0.25). Within the Brazilian subpopulation (n=74), a significant age imbalance between the vilobelimab and placebo group was detected (median 53.5 years in the vilobelimab group vs 44.5 years in the placebo group). Occurrence of treatment-emergent adverse events between regions was similar.</p><p><strong>Conclusion: </strong>The most apparent 28-day all-cause mortality benefit for vilobelimab was in western Europe. Age imbalance between treatment groups in Brazil may have resulted in a lower efficacy signal for vilobelimab in South America compared with other regions. Overall, vilobelimab demonstrated a favourable safety profile and reduced mortality in critically ill, intubated COVID-19 patients, with regional variations influencing outcomes.</p>","PeriodicalId":9048,"journal":{"name":"BMJ Open Respiratory Research","volume":"12 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010313/pdf/","citationCount":"0","resultStr":"{\"title\":\"Regional comparison of efficacy and safety for vilobelimab in critically ill, invasively mechanically ventilated COVID-19 patients.\",\"authors\":\"Endry H T Lim, Diederik van de Beek, Sanne de Bruin, Simon Rückinger, Claus Thielert, Renfeng Guo, Bruce P Burnett, Matthijs C Brouwer, Robert Zerbib, Camilla Chong, Niels C Riedemann, Alexander P Vlaar\",\"doi\":\"10.1136/bmjresp-2023-002206\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Vilobelimab, a first in class C5a-specific monoclonal antibody, improved 28-day and 60-day mortality in intubated COVID-19 patients in PANAMO, a phase 3 randomised, double-blind, placebo-controlled multicentre study. All-cause mortality was pre-specified to be analysed pooling by region (western Europe, South America, South Africa/Russia).</p><p><strong>Methods: </strong>Critically ill, invasively mechanically ventilated COVID-19 patients were randomised in a 1:1 ratio within 48 hours of intubation to receive vilobelimab treatment (six, 800 mg intravenous infusions) or placebo on top of standard of care. We analysed the efficacy and safety of vilobelimab based on prespecified geographic regions.</p><p><strong>Results: </strong>368 patients were randomised and analysed: 177 in the vilobelimab group and 191 in the placebo group. In western Europe (n=209), 28-day all-cause mortality was significantly lower in the vilobelimab group (21%) compared with placebo (37%) (HR 0.51 (95% CI: 0.30, 0.87), p=0.014). In South America (n=126), mortality was similar between groups (40% vs 37%; HR 0.94 (95% CI: 0.53, 1.67), p=0.83). In South Africa/Russia (n=33), mortality was 69% in the vilobelimab group and 87% in the placebo group (HR 0.62 (95% CI: 0.28, 1.38), p=0.25). Within the Brazilian subpopulation (n=74), a significant age imbalance between the vilobelimab and placebo group was detected (median 53.5 years in the vilobelimab group vs 44.5 years in the placebo group). Occurrence of treatment-emergent adverse events between regions was similar.</p><p><strong>Conclusion: </strong>The most apparent 28-day all-cause mortality benefit for vilobelimab was in western Europe. Age imbalance between treatment groups in Brazil may have resulted in a lower efficacy signal for vilobelimab in South America compared with other regions. Overall, vilobelimab demonstrated a favourable safety profile and reduced mortality in critically ill, intubated COVID-19 patients, with regional variations influencing outcomes.</p>\",\"PeriodicalId\":9048,\"journal\":{\"name\":\"BMJ Open Respiratory Research\",\"volume\":\"12 1\",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-04-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010313/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMJ Open Respiratory Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/bmjresp-2023-002206\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Respiratory Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/bmjresp-2023-002206","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
Regional comparison of efficacy and safety for vilobelimab in critically ill, invasively mechanically ventilated COVID-19 patients.
Background: Vilobelimab, a first in class C5a-specific monoclonal antibody, improved 28-day and 60-day mortality in intubated COVID-19 patients in PANAMO, a phase 3 randomised, double-blind, placebo-controlled multicentre study. All-cause mortality was pre-specified to be analysed pooling by region (western Europe, South America, South Africa/Russia).
Methods: Critically ill, invasively mechanically ventilated COVID-19 patients were randomised in a 1:1 ratio within 48 hours of intubation to receive vilobelimab treatment (six, 800 mg intravenous infusions) or placebo on top of standard of care. We analysed the efficacy and safety of vilobelimab based on prespecified geographic regions.
Results: 368 patients were randomised and analysed: 177 in the vilobelimab group and 191 in the placebo group. In western Europe (n=209), 28-day all-cause mortality was significantly lower in the vilobelimab group (21%) compared with placebo (37%) (HR 0.51 (95% CI: 0.30, 0.87), p=0.014). In South America (n=126), mortality was similar between groups (40% vs 37%; HR 0.94 (95% CI: 0.53, 1.67), p=0.83). In South Africa/Russia (n=33), mortality was 69% in the vilobelimab group and 87% in the placebo group (HR 0.62 (95% CI: 0.28, 1.38), p=0.25). Within the Brazilian subpopulation (n=74), a significant age imbalance between the vilobelimab and placebo group was detected (median 53.5 years in the vilobelimab group vs 44.5 years in the placebo group). Occurrence of treatment-emergent adverse events between regions was similar.
Conclusion: The most apparent 28-day all-cause mortality benefit for vilobelimab was in western Europe. Age imbalance between treatment groups in Brazil may have resulted in a lower efficacy signal for vilobelimab in South America compared with other regions. Overall, vilobelimab demonstrated a favourable safety profile and reduced mortality in critically ill, intubated COVID-19 patients, with regional variations influencing outcomes.
期刊介绍：
BMJ Open Respiratory Research is a peer-reviewed, open access journal publishing respiratory and critical care medicine. It is the sister journal to Thorax and co-owned by the British Thoracic Society and BMJ. The journal focuses on robustness of methodology and scientific rigour with less emphasis on novelty or perceived impact. BMJ Open Respiratory Research operates a rapid review process, with continuous publication online, ensuring timely, up-to-date research is available worldwide. The journal publishes review articles and all research study types: Basic science including laboratory based experiments and animal models, Pilot studies or proof of concept, Observational studies, Study protocols, Registries, Clinical trials from phase I to multicentre randomised clinical trials, Systematic reviews and meta-analyses.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
