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. 2024 Apr 15;58(6):7-13.
doi: 10.47895/amp.vi0.6175. eCollection 2024.

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

Eric Jason B Amante  1   2 , Aileen S David-Wang  1   2 , Michael L Tee  1   2 , Felix Eduardo R Punzalan  1   2 , John C Añonuevo  1   2 , Lenora C Fernandez  1   2 , Albert B Albay Jr  1   2 , John Carlo M Malabad  2 , Fresthel Monica M Climacosa  3 , A Nico Nahar I Pajes  1   2 , Patricia Maria Gregoria M Cuaño  1   2 , Marissa M Alejandría  1   2
Affiliations

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

Eric Jason B Amante et al. Acta Med Philipp. .

Abstract

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.

Keywords: COVID-19; IL-6; randomized trial; tocilizumab.

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Conflict of interest statement

All authors declared no conflicts of interest.

Figures

Figure 1
Figure 1
Number of patients screened, enrolled, randomized, and included in the analysis of this study.
See this image and copyright information in PMC

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