<h4>SUMMARY</h4> <h4>Background</h4> Tocilizumab is a monoclonal antibody that binds to the receptor for interleukin (IL)-6, reducing inflammation, and is commonly used to treat rheumatoid arthritis. We evaluated the safety and efficacy of tocilizumab in adult patients admitted to hospital with COVID-19 with evidence of both hypoxia and systemic inflammation. <h4>Methods</h4> 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 [CRP] ≥75 mg/L) were eligible for randomisation to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg to 800 mg (depending on weight) given intravenously. A second dose could be given 12 to 24 hours 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 ). <h4>Findings</h4> Between 23 April 2020 and 24 January 2021, 4116 adults were included in the assessment of tocilizumab, including 562 (14%) patients receiving invasive mechanical ventilation, 1686 (41%) receiving non-invasive respiratory support, and 1868 (45%) receiving no respiratory support other than oxygen. Median CRP was 143 [IQR 107-204] mg/L and 3385 (82%) patients were receiving systemic corticosteroids at randomisation. Overall, 596 (29%) of the 2022 patients allocated tocilizumab and 694 (33%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·86; 95% confidence interval [CI] 0·77-0·96; p=0·007). Consistent results were seen in all pre-specified subgroups of patients. In particular, a clear mortality benefit was seen in those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital alive within 28 days (54% vs. 47%; rate ratio 1·22; 95% CI 1·12-1·34; 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 (33% vs. 38%; risk ratio 0·85; 95% CI 0·78-0·93; p=0·0005). <h4>Interpretation</h4> In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the level of respiratory support and were additional to the benefits of systemic corticosteroids. <h4>Funding</h4> UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).
RECOVERY Collaborative Group