Abstract
SummaryBackgroundIn 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.MethodsThis 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).FindingsBetween 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).InterpretationIn 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.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Highlights
The majority of SARS-CoV-2 infections are either asymptomatic or result in only mild disease.[1]
Among COVID-19 patients admitted to UK hospitals in spring, 2020, the case fatality rate was over 26%, and was in excess of 37% in patients requiring invasive mechanical ventilation.[2]
Hypoxic respiratory failure in patients with COVID-19 is associated with evidence of systemic inflammation, including release of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumour necrosis factor α, and elevated concentrations of D-dimer, ferritin, and C-reactive protein (CRP).[3,4]
Summary
The majority of SARS-CoV-2 infections are either asymptomatic or result in only mild disease.[1]. Among COVID-19 patients admitted to UK hospitals in spring, 2020, the case fatality rate was over 26%, and was in excess of 37% in patients requiring invasive mechanical ventilation.[2]. Hypoxic respiratory failure in patients with COVID-19 is associated with evidence of systemic inflammation, including release of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumour necrosis factor α, and elevated concentrations of D-dimer, ferritin, and C-reactive protein (CRP).[3,4] The host immune response is thought to play a key role in driving an acute inflammatory pneumonic process with diffuse alveolar damage, myeloid cell infiltrates, and microvascular thrombosis.[5] The beneficial effects of dexamethasone and other corticosteroids in COVID-19 patients with hypoxic lung damage suggest that other, more specific, immunom odulatory agents might provide additional improvements in clinical outcomes.[6,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
