Tocilizumab vs bevacizumab in critically ill COVID-19 patients: Registry-based prospective study

Abstract

Background:

Tocilizumab, an interleukin-6 (IL-6) inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, have been used in critically ill COVID-19 patients for cytokine storm. We performed a registry-based prospective study to compare the efficacy of these two drugs.

Methods:

Virologically confirmed hospitalised patients with severe COVID-19 who received either tocilizumab or bevacizumab have been included. Management details and outcomes were recorded. The primary outcome was in-hospital deaths and secondary outcomes were 30-day deaths, changes in oxygen requirement at 48 h of drug administration and duration of intensive care unit stay. Descriptive statistics are reported.

Results:

One thousand three hundred forty-five COVID-19 patients were hospitalised during the study period, 87 with severe COVID-19 received tocilizumab (n = 62) or bevacizumab (n = 25). Patients in the tocilizumab group were older (62.6 ± 11 vs 53.2 ± 14, p = 0.001) with more cardiovascular disease and no significant differences in clinical features, laboratory investigations, or radiological and biochemical markers of disease severity. Oxygenation, ventilatory support and proning were similar as were supportive therapies (steroids, remdesivir, anticoagulants; p > 0.05). In-hospital deaths in tocilizumab vs bevacizumab group were 47 (75.8%) vs 12 (48.0%; p = 0.012) with unadjusted hazard ratio (HR) 1.91 (95% confidence interval (CI) 0.99–3.65, p = 0.050) and age-adjusted HR 1.76 (95% CI 0.90–3.44, p = 0.097). Secondary outcome of 30-day death was also more in tocilizumab group: 49 (79.0%) vs 13 (52.0%; p = 0.011). Within-group comparison showed that PaO₂:FiO₂ at 48-h of drug administration was better in bevacizumab group (p = 0.003) compared to tocilizumab (p = 0.651).

Conclusion:

VEGF inhibitor bevacizumab led to significantly better ventilatory outcomes and lower in-hospital and 30-day deaths compared to IL-6 inhibitor tocilizumab in severely ill COVID-19 patients. Randomised studies are required to confirm these findings.