Key points are not available for this paper at this time.
Background: Several targeted therapies such as anakinra, tocilizumab, and janus kinase (JAK) inhibitors were found to be effective in patients with COVID-19 associated cytokine storm. Objectives: Herein, we aimed to evaluate the safety and efficacy of combination of high-dose intravenous anakinra treatment and baricitinib in patients with critical COVID-19. Methods: Study population consisted of patients with positive polymerase chain reaction and computer tomography findings compatible with COVID-19 as well as critical non-intubated illness requiring high flow nasal oxygen supplement. Hyperinflammatory state of the patients were scored according to COVID-19 hyperinflammatory syndrome score (cHIS score). All patients received background glucocorticoid treatment with methylprednisolone 80 mg/day intravenously. Anakinra was initiated in patients who did not respond to two days of corticosteroid treatment or concomitantly in high risky patients with 400 mg/day intravenously in two divided dose and gradually increased to 1600 mg/day (10 mg/kg/day) if necessary. In combination group, baricitinib was started in 2 mg/day and gradually increased to 8 mg/day in addition to steroid and anakinra in patients with unresponsive to anakinra at least three days. Age, gender, disease severity, and cHIS scores matched patients receiving anakinra defined as control group. Results: Data of 15 patients in combination group and 43 patients in control group were evaluated and included into the study. Of these patients 73.3% was male in combination arm and 72.1% in control group (p=0.9). Overall mortality was 46.7% (n=7) in combination arm and 69.8% (n=30) in control group although it was not statistically significant (p=0.1). Similarly, need of intubation was also lower in combination arm (46.7%) compared to control group (69.8%), it was not significantly different (p=0.1). ICU admission was significantly lower in combination (46.7%, n=7) arm than control group (76.7%, n=33) (p=0.03, Odds ratio OR:4.7). Development of severe infection (20%, n=3 vs 25%, n=9/36), pulmonary embolism (6.7%, n=1 vs 0), myocardial infarction (6.7%, n=1 vs 2.6%, n=1/38) and pneumothorax (13.3%, n=2 vs 2.6%, n=1/38) were not different between two groups (p=0.7, p=0.3, p=0.5 and p=0.2). In survival analysis, mortality rate was significantly lower in combination arm than control group (Log-Rank:p=0.04; Figure 1). Conclusion: Our study emphasizes no additional safety signal including severe infection, thrombosis, and cardiovascular events with combination group. Furthermore, combination therapy tended to reduce mortality in patients with critical COVID-19 in our study. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.
Murat Bektaş (Sat,) studied this question.