Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study

Abstract

Critically ill patients with COVID-19 may suffer from a cytokine release syndrome (CRS) characterized by remarkably high levels of interleukin 6 (IL-6). We assessed the effects of tocilizumab, an IL-6 receptor antagonist, on intra-hospital mortality and development of positive cultures in patients with COVID-19 admitted to the ICU. In this study, patients with COVID 19 admitted in the ICU who were treated with tocilizumab plus standard care were enrolled and compared to controls. Main outcome: 1) intra-hospital mortality; Secondary Outcomes: 1) the need for renal replacement therapy, 2) use of antibiotics and positive culture, and 3) inflammatory and oxygenation markers. Results: There was no difference in mortality, need for renal replacement therapy, use of antibiotics or positive cultures between the two groups. The use of corticosteroids was more frequent in the treatment group. Levels of C-reactive protein (CRP) and WBC (white blood cells) counts declined significantly faster in the treatment group. Oxygenation markers rose significantly higher in patients in the tocilizumab group as compared to controls. Conclusion: tocilizumab was associated with rapid improvement in oxygenation and a faster decrease of CRP and WBC counts in patients with COVID-19 and should be evaluated as rescue therapy for patients with progressive disease

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version)

“…A non-randomized controlled study (29 vs. 24) showed that after adjusting for age and mechanical ventilation, use of TCZ (400 mg, iv., two doses) was not associated with mortality of COVID-19 patients in ICU (OR = 3.97, 95% CI 0.28-57.2, P = 0.3), and no adverse events were reported that could be directly related to TCZ [79]. A propensity-score matched cohort study (74 vs. 148 severe/critical patients) found TCZ use was associated with a better overall survival (HR = 0.499, 95% CI 0.262-0.952, P = 0.035), but the length of hospital stay with TCZ was longer (dose: 8 mg/kg, HR = 1.658, 95% CI 1.088-2.524, P = 0.019).…”

The role of Interleukin 6 inhibitors in therapy of severe COVID-19

“…Carvalhoet et al [ 95 ] compared the efficacy of TCZ in 28 patients with severe COVID-19 in the ICU and in 24 patients in the control group. Despite the initially more severe condition (the need for GC, mechanical ventilation, a marked decrease in gas exchange) of patients in the TCZ group, there was no increase in mortality (p = 0.3) and in the incidence of infectious complications in theTCZ group.…”

Beneficial and harmful outcomes of tocilizumab in severe COVID-19: a systematic review and meta-analysis

“…A total of 781 articles were identified in our search. Of these, 81 qualified for full-text review following title and abstract screening, of which 57 [11-67] were included in the analysis. The PRISMA flow diagram is detailed in Figure 1.…”

“…Of the total of 57 studies included, 12 were prospective and 45, retrospective. In 30 of these cohort investigations, a control group was not described [10-38] and 27 added a comparison group [40-67]. The overall results provided data from 8,128 hospitalized patients with COVID-19: 4,021 TCZ-treated, in addition to standard of care (SOC) (including 711 patients admitted to ICU), and 4,107 only receiving SOC (including 694 patients admitted to ICU).…”

“…Accordingly, the use of immunomodulatory agents such as tocilizumab (TCZ), a monoclonal antibody to the recombinant human IL-6 receptor, was initially reported as successful among 21 patients in China [11]. Since then, an emerging number of observational studies from America and Europe have been published or registered assessing the effect of TCZ in severe COVID-19 [12-67]. In most of them, the authors report an association between earlier use of TCZ and reduced mortality; however, interpretation of these results is limited because several of them did not describe a comparison group.…”