Evaluation of Early Tocilizumab Effect on Multiorgan Dysfunction in Critically Ill Patients With COVID-19: A Propensity Score-Matched Study

Abstract

Background: Tocilizumab (TCZ) has been proposed as potential rescue therapy for severe COVID-19. No previous study has primarily assessed the role of TCZ in preventing severe COVID-19-related multiorgan dysfunction. Hence, this multicenter cohort study aimed to evaluate the effectiveness of TCZ early use versus standard of care in preventing severe COVID-19-related multiorgan dysfunction in COVID-19 critically ill patients during intensive care unit (ICU) stay. Methods: A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the ICUs. Patients were categorized into two groups, the treatment group includes patients who received early TCZ therapy within 24 hours of ICU admission and the control group includes patients who received standard of care. The primary outcome was the multiorgan dysfunction on day three of the ICU admission. The secondary outcomes were 30-day, and in-hospital mortality, ventilator-free days, hospital length of stay (LOS), ICU LOS, and ICU-related complications. Results: After propensity score matching, 300 patients were included in the analysis based on predefined criteria with a ratio of 1:2. Patients who received TCZ had lower multiorgan dysfunction score on day three of ICU admission compared to the control group (beta coefficient: −0.13, 95% CI: −0.26, −0.01, P-value = 0.04). Moreover, respiratory failure requiring MV was statistically significantly lower in patients who received early TCZ compared to the control group (OR 0.52; 95% CI 0.31, 0.91, P-value = 0.02). The 30-day and in-hospital mortality were significantly lower in patients who received TCZ than those who did not (HR 0.56; 95% CI 0.37, 0.85, P-value = 0 .006 and HR 0.54; 95% CI 0.36, 0.82, P-value = 0.003, respectively). Conclusion: In addition to the mortality benefits associated with early TCZ use within 24 hours of ICU admission, the use of TCZ was associated with a significantly lower multiorgan dysfunction score on day three of ICU admission in critically ill patients with COVID-19.

Baricitinib versus tocilizumab in critically ill COVID‐19 patients: A retrospective cohort study

“…23 Conversely, multiple studies have been published comparing tocilizumab with placebo in a similar patient population. 8,10,14-19, 22 The largest such trial, the REMAP-CAP trial, concluded that tocilizumab was associated with improved outcomes, including in-hospital survival, reporting a 99.6% probability of superiority of tocilizumab compared with control. 8 Although a benefit has been seen with each of these agents in treating critically ill patients with COVID-19 pneumonia, to date, only smaller observational studies and one randomized controlled trial (RCT) have been published comparing the safety and efficacy of these two agents to each other.…”

“…Unfortunately, this study was stopped prematurely, so conclusions on clinical outcomes were unable to be drawn 23 . Conversely, multiple studies have been published comparing tocilizumab with placebo in a similar patient population 8,10,14–19,22 . The largest such trial, the REMAP‐CAP trial, concluded that tocilizumab was associated with improved outcomes, including in‐hospital survival, reporting a 99.6% probability of superiority of tocilizumab compared with control 8…”

“…Early administration of tocilizumab, within 24 h of ICU admission, may also have added clinical benefits. 8, 22 The JAK inhibitor baricitinib similarly has promising results for these patients, with a demonstrated reduction in mortality compared with usual care. 11,12,20,21 In August 2021, a national drug shortage of tocilizumab was announced, drastically limiting available drug supply to hospitals.…”

“…When compared with placebo, the IL‐6 inhibitor tocilizumab has reduced mortality, increased organ support‐free days, and decreased hospital length of stay. Early administration of tocilizumab, within 24 h of ICU admission, may also have added clinical benefits 8,22 . The JAK inhibitor baricitinib similarly has promising results for these patients, with a demonstrated reduction in mortality compared with usual care 11,12,20,21 .…”

Efficacy of interleukin-6 inhibitors as a tool for preventive anti-inflammatory therapy for COVID-19

“…Близкие данные были получены в более поздней работе Aljuhani O, et al (2023) -по данным авторов введение тоцилизумаба в первые 24 часа пребывания пациента в ОРИТ способствовало выраженному снижению дыхательной недостаточности у пациентов с COVID-19 в критическом состоянии по сравнению с контрольной группой (стандартная терапия без анти-ИЛ-6 МАТ) при оценке на третий день: отношение шансов, ОШ: 0,52; 95 % ДИ: от 0,31, до 0,91, р=0,02. 30-дневная и внутрибольничная смертность также были значительно ниже у пациентов, получавших тоцилизумаб в сравнении с контролем (ОШ: 0,56; 95 % ДИ: от 0,37 до 0,85, р=0,006 и ОШ: 0,54; 95 % ДИ: от 0,36 до 0,82, р=0,003 соответственно) [33].…”