Eric Jason B Amante, Aileen S David-Wang, Michael L Tee, Felix Eduardo R Punzalan, John C Añonuevo, Lenora C Fernandez, Albert B Albay, John Carlo M Malabad, Fresthel Monica M Climacosa, A Nico Nahar I Pajes, Patricia Maria Gregoria M Cuaño, Marissa M Alejandría
{"title":"静脉注射托珠单抗与标准护理对比治疗严重和危重 COVID-19 相关肺炎:单中心、双盲、安慰剂对照 3 期试验。","authors":"Eric Jason B Amante, Aileen S David-Wang, Michael L Tee, Felix Eduardo R Punzalan, John C Añonuevo, Lenora C Fernandez, Albert B Albay, John Carlo M Malabad, Fresthel Monica M Climacosa, A Nico Nahar I Pajes, Patricia Maria Gregoria M Cuaño, Marissa M Alejandría","doi":"10.47895/amp.vi0.6175","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors.</p><p><strong>Objectives: </strong>This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease.</p><p><strong>Methods: </strong>This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner.</p><p><strong>Results: </strong>Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups.There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status.</p><p><strong>Conclusion: </strong>The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.</p>","PeriodicalId":6994,"journal":{"name":"Acta Medica Philippina","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151130/pdf/","citationCount":"0","resultStr":"{\"title\":\"Intravenous Tocilizumab versus Standard of Care in the Treatment of Severe and Critical COVID-19-related Pneumonia: A Single-center, Double-blind, Placebo-controlled, Phase 3 Trial.\",\"authors\":\"Eric Jason B Amante, Aileen S David-Wang, Michael L Tee, Felix Eduardo R Punzalan, John C Añonuevo, Lenora C Fernandez, Albert B Albay, John Carlo M Malabad, Fresthel Monica M Climacosa, A Nico Nahar I Pajes, Patricia Maria Gregoria M Cuaño, Marissa M Alejandría\",\"doi\":\"10.47895/amp.vi0.6175\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors.</p><p><strong>Objectives: </strong>This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease.</p><p><strong>Methods: </strong>This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner.</p><p><strong>Results: </strong>Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups.There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status.</p><p><strong>Conclusion: </strong>The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.</p>\",\"PeriodicalId\":6994,\"journal\":{\"name\":\"Acta Medica Philippina\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-04-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151130/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Medica Philippina\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.47895/amp.vi0.6175\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Medica Philippina","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.47895/amp.vi0.6175","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
Intravenous Tocilizumab versus Standard of Care in the Treatment of Severe and Critical COVID-19-related Pneumonia: A Single-center, Double-blind, Placebo-controlled, Phase 3 Trial.
Background: Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors.
Objectives: This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease.
Methods: This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner.
Results: Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups.There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status.
Conclusion: The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.