Immunomodulators including tocilizumab and baricitinib have been used for the treatment of severe COVID-19, however, studies comparing their efficacy are lacking. We aimed to compare their safety and effectiveness in severe COVID-19.

Methods:All consecutive non-ICU hospitalized severe COVID-19 patients, from May 2021 to July 2022, who were admitted to our departments and received baricitinib or tocilizumab as add-on therapy, were included retrospectively. Demographics, clinical and laboratory data were recorded. Primary outcomes were mortality or intubation on day 14, time to oxygen therapy weaning and duration of hospitalization. Safety was measured as treatment-related adverse events.

Results: Among 321 COVID-19 patients [mean age (SD) 62.4 (14.7) years]; 241 (75%) received baricitinib and 80 (25%) tocilizumab. Patients who received tocilizumab presented significantly higher risk of mortality or intubation on day 14, compared to the baricitinib group after adjusting for age, sex, vaccination, Charlson comorbidity index, body mass index, remdesivir administration and WHO ordinal scale at enrolment [OR:2.42, 95%CI:1.18-4.98]. They also had longer hospital stay (average 7 days, 95%CI:2.91-11.47) compared to baricitinib and prolonged oxygen therapy by 8 days [b-coef: 7.63, 95%CI:5.01-10.23] after adjustment. No difference concerning secondary bacterial infections was detected, while drug-induced liver injury was significantly more common in tocilizumab.

Conclusions: The data presented point at a difference in effectiveness between baricitinib and tocilizumab, favoring baricitinib in severe COVID-19. Clinical randomized trials are needed to confirm our results.