Discussion
Baricitinib, is a selective JAK1 inhibitor, decreases production of several proinflammatory cytokines including IL-2, IL-6, IL-7, TNF-α, and type 1 IFNs (7). Although baricitinib decreases many cytokine levels as mentioned above it does not affect to IL-1 levels. High-dose intravenous anakinra treatment was found to be safe and effective in patients with severe COVID-19 in our previous study (8). In the current study we added baricitinib to the extremely ill COVID-19 patients who had refractory to both steroids and high-dose anakinra. The rationale of the current protocol is more effective suppression of cytokine production in patients had extremely higher mortality. 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. We emphasize that in this study, combination therapy was applied only to critically ill patients and did not include milder disease therefore this finding may not be generalized to milder cases.
In conclusion, combination therapy of high-dose anakinra and baricitinib may be an adequate treatment option in patients with COVID-19 who had critical disease and no additional safety signal.
Table 1 : Clinical and laboratory features and outcomes of study participants