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