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BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.
METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein =75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).
FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001).
INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.
FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Interesting but caution is needed with open-label studies.
An interesting article that strikes me as the new shiny object that will probably turn out to be not much progress against COVID-19.
Tocilizumab has clearly joined the very select group of interventions that are effective in mitigating severe COVID-19. The criteria for whom benefit is observed are reasonably clear and the outcomes convincing. An important contribution to the literature.
Definitely a relevant and well done high-quality RCT.
This is a landmark trial that, along with REMAP-CAP, should change practice for COVID-19. Methodologically rigorous and clinically meaningful. As an intensive care physician, this is immediately and directly relevant to my practice.
The findings of this large randomized trial give more confidence in considering the use of tocilizumab in selected patients infected with COVID-19 who have respiratory compromise and the level of inflammation as measured by the CRP herein. The benefits of treatment on 28-day mortality seem to favor men and the elderly and the population enrolled was overwhelmingly Caucasian (fig. 3). The findings of this trial may not be generalizable to other parts of the world experiencing this pandemic.