Tocilizumab in COVID-19: some clarity amid controversy: Lancet

Hyperactivation of the immune response, including release of pro-inflammatory cytokines such as interleukin-6 (IL-6), might play a key role in the pathophysiology of severe illness from COVID-19. Consistent with this notion, one of the few therapies that reduces mortality in hospitalised patients with COVID-19 is the corticosteroid, dexamethasone.2 Accordingly, there has been great interest in examining whether treatment with additional, more targeted anti-inflammatory agents beyond steroids could provide further benefit.
Tocilizumab is a recombinant humanised monoclonal antibody that inhibits binding of IL-6 to both membrane and soluble IL-6 receptors. Early observations from China suggested improved outcomes in hospitalised patients with COVID-19 who received tocilizumab. These preliminary reports were followed by large observational studies in critically ill patients with COVID-19, which suggested a mortality benefit with tocilizumab. Subsequent randomised clinical trials examining tocilizumab reported conflicting results, but these trials differed considerably in size, study design, and illness severity of the patients enrolled. For instance, several initial trials failed to show a mortality benefit for tocilizumab, but these trials enrolled fewer than 300 patients each and were thus underpowered to detect differences in death between groups.8 Additional limitations of early trials were exclusion of critically ill patients and imbalances in the use of steroids between tocilizumab-treated and tocilizumab-untreated patients.9 The Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) study published in 2021 was, until now, the largest trial (n=803) to examine tocilizumab in COVID-19, and showed a survival benefit.10 However, as REMAP-CAP was limited to critically ill patients, the role of tocilizumab for hospitalised but non-critically ill patients with COVID-19 remained unclear.