Tocilizumab Efficacy Across Inflammatory Subphenotypes in COVID-19-Related Acute Respiratory Distress Syndrome

OBJECTIVES: This study evaluated whether the established efficacy of tocilizumab, an interleukin-6 (IL-6) receptor antagonist, differs between the hypoinflammatory and hyperinflammatory subphenotypes. DESIGN: Retrospective analysis of data from three biobanks. SETTING: ICUs of three university teaching hospitals in the Netherlands. PATIENTS: Mechanically ventilated patients with COVID-19. INTERVENTIONS: Tocilizumab administration vs. no administration. MEASUREMENTS AND MAIN RESULTS: A total of 561 patients were included. Based on a classifier model incorporating IL-6, tumor necrosis factor receptor 1, and bicarbonate, 95% were classified as Hypoinflammatory and 5% as Hyperinflammatory. Tocilizumab was associated with a significant reduction in 30-day mortality in the overall cohort, even after adjustment for confounders ( p = 0.014). However, there was no evidence that treatment effectiveness differed between the two subphenotypes ( p = 0.59). CONCLUSIONS: In this cohort, tocilizumab significantly reduced 30-day mortality overall. Although the number of Hyperinflammatory patients was low, there was no evidence that its efficacy differed between inflammatory subphenotypes. These findings underscore the importance of including both subphenotypes in future trials evaluating the differential effects of tocilizumab.