Tocilizumab is licensed for use in rheumatoid arthritis but is also appears to have potentially useful role in those with COVID-19.
Disease progression among those hospitalised with COVID-19 often leads to hypoxic respiratory failure which is associated with systemic inflammation and the release of pro-inflammatory cytokines including interleukin-6 (IL-6). Hypoxic respiratory failure necessitates the use of prolonged ventilatory support and systemic corticosteroids. However, given that the condition is associated with an increased level of pro-inflammatory cytokines, could add-on therapy with immunomodulatory agents such as tocilizumab, which block of IL-6 signally, offer mortality benefits? This is one of the questions being addressed by the randomised evaluation of COVID-19 therapy (RECOVERY) trial which has been established to examine the efficacy of a range of interventions for hospitalised patients infected with the virus. One arm of the study includes the use of tocilizumab. Any patient admitted to hospital because of COVID-19 is eligible for inclusion into the RECOVERY trial if they have either clinically suspected or laboratory confirmed COVID-19 and no medical history which, in the opinion of the treating physician, might put them at a significant risk if they participated in the trial. To be considered for treatment with tocilizumab, patients should have evidence of clinical deterioration of COVID-19 defined by an oxygen saturation less than 92% or receiving oxygen therapy, at which point they are randomised to usual care or tocilizumab as a single intravenous dose (based on the patient’s weight) over 60 minutes. A second dose can be administered the following day, based on the opinion of the treating physician. The primary outcome for the trial is all-cause mortality 28 days after randomisation.
Findings
Between April 2020 and January 2021, over 4,000 patients have been recruited into the tocilizumab arm of RECOVERY; 2022 patients with a mean age of 63.6 years (66% male) being assigned to tocilizumab and 2094 to usual care. At the time of randomisation, most patients (45%) in the tocilizumab arm were in receipt of no additional support other than oxygen though 41% required non-invasive respiratory support and the majority (82%) of patients in both groups were already receiving systemic corticosteroids. The interim results demonstrated a significant reduction in mortality among those assigned to tocilizumab compared to usual care (29% vs 33%) and use of the drug was associated with a higher probability of being discharged alive within 28 days (54% vs 47%). Furthermore, among those not on invasive mechanical ventilation at baseline, there was a reduction in the risk of progression to ventilation compared to usual care (33% vs 38%).
The authors concluded that in patients with severe COVID-19, tocilizumab reduced mortality and the need for invasive mechanical ventilation and that these benefits are additional to the use of systemic corticosteroids.
Citation
The RECOVERY Collaborative Group. Tocilizumab for COVID-19. MedRxiv https://doi.org/10.1101/2021.02.11.21249258
