#VisualAbstract: Tocilizumab may improve survival in COVID-19 patients with hypoxia and systemic inflammation

1. Compared to usual care, fewer patients in the tocilizumab group died within 28 days of randomization.

2. Patients allocated tocilizumab were more likely to be discharged from the hospital within 28 days.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Hypoxic respiratory failure in patients with COVID-19 is associated with systemic inflammation, alveolar damage, and microvascular thrombosis. Although dexamethasone and other corticosteroids have shown a beneficial effect, the use of tocilizumab – an anti-interleukin (IL)-6 receptor monoclonal antibody – in COVID-19 patients with systemic inflammation is under investigation. This randomized controlled trial aimed to evaluate the effects of tocilizumab in hospitalized COVID-19 patients with hypoxia and systemic inflammation. The primary outcome was all-cause mortality at 28 days of randomization, while key secondary outcomes included time to discharge from hospital, receipt of invasive mechanical ventilation, and death. According to study results, patients in the tocilizumab group were less likely to die at 28 days and more likely to be discharged from the hospital compared to the usual care group. This trial was limited by lack of regular follow-up. For instance, clinical outcomes were only assessed at 28 days and 6 months after randomization. This may have led to a loss of follow-up for some patients and recall bias among those who completed the form. Nonetheless, this study provided valuable insight into the use of tocilizumab to improve survival among hospitalized patients with COVID-19.

Click to read the study in The Lancet

Relevant Reading: Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia

In-depth [randomized controlled trial]: Between Apr 23, 2020, and Jan 24, 2021, 21 550 patients were assessed for eligibility across 131 UK sites. Included patients were those with clinically suspected or laboratory confirmed SARS-CoV-2 infection, hypoxia (defined as SaO₂ < 92% on room air), and systemic inflammation (C-reactive protein ³ 75 mg/L). Those with known hypersensitivity to tocilizumab and active tuberculosis infection were not eligible. Altogether, 4116 patients (2022 in the tocilizumab group and 2094 in the usual care group) were included in the intention-to-treat (ITT) analysis. Tocilizumab was administered as a single intravenous infusion at doses determined by patients’ bodyweight.

The mean age of participants was 63.6 years (standard deviation [SD] 13.6). At randomization, 82% of patients were receiving corticosteroids. The primary outcome of all-cause mortality within 28 days of randomization was lower in the tocilizumab group compared to the usual care group (31% vs. 35%, rate ratio [RR] 0.85, 95% confidence interval [CI] 0.76-0.94, p=0.0028). This was the case for all prespecified subgroups, including patients with a positive SARS-CoV-2 test result and those receiving systemic corticosteroids. Allocation to tocilizumab was associated with a greater probability of discharge from hospital within 28 days (57% vs. 50%, RR 1.22, 95% CI 1.12-1.33, p<0.0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated to tocilizumab were less likely to reach the secondary outcome of invasive mechanical ventilation or death (35% vs. 42%, RR 0.84, 95% CI 0.77-0.92, p<0.0001). In prespecified analyses, tocilizumab was also found to reduce the use of hemodialysis and hemofiltration compared to usual care (6% vs. 8%, RR 0.72, 95% CI 0.58-0.90, p=0.0046). Overall, findings from this study suggest that use of tocilizumab may improve survival and other clinical outcomes in hospitalized COVID-19 patients with hypoxia and systemic inflammation.

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