Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
In patients with hypoxia and evidence of systemic inflammation (C-reactive protein ≥75 mg/L), the addition of tocilizumab to usual standard of care (82% receiving systemic corticosteroids) reduced 28-day mortality (31% v 35%; rate ratio 0.85; 95% CI 0.76–0.94; p=0.0028).
Source:
The Lancet
SPS commentary:
A related Comment notes that the early RCTs of tocilizumab in Covid-19 varied considerably in size, study design and illness severity, with conflicting results. Until now, the REMAP-CAP study was the largest trial to examine tocilizumab in Covid-19, but it was limited to critically ill patients. This latter study was the basis of the first Interim Position Statement on the use of tocilizumab for patients admitted to ICU with Covid-19 pneumonia, issued by the Department of Health and Social care in November 2020.
The RECOVERY trial is the largest trial of tocilizumab in Covid-19 to date, randomising 4116 hospitalised adults to tocilizumab or usual care. Most were receiving systemic corticosteroids at the time of randomisation, in contrast to some of the earlier studies. As well as a statistically significant benefit for the primary endpoint of 28-day mortality, tocilizumab was also associated with a greater probability of discharge within 28 days (57% v 50%; RR 1.22; 1.12-1.33; p<0.0001) and reduced risk of progression to invasive mechanical ventilation or death, in those not receiving mechanical ventilation at baseline (35% v 42%; RR 0.84; 0.77-0.92; p<0.0001). The UK Interim Clinical Commissioning Policy for tocilizumab was updated as a result of this study, to recommend its use in a wider group of patients hospitalised with Covid-19.
The NICE Covid-19 rapid guideline on Managing Covid-19 recommends tocilizumab be offered to adults in hospital with COVID-19 if all of the following apply:
- they are having or have completed a course of corticosteroids such as dexamethasone, unless they cannot have corticosteroids
- they have not had another interleukin-6 inhibitor during this admission
- there is no evidence of a bacterial or viral infection (other than SARS-CoV-2) that might be worsened by tocilizumab.
And they either:
- need supplemental oxygen and have a C-reactive protein level of 75 mg/litre or more, or
- are within 48 hours of starting high-flow nasal oxygen, continuous positive airway pressure, non-invasive ventilation or invasive mechanical ventilation.