Survival Benefit of High Dose Versus Usual Dose of Baricitinib in Hospitalized Patients with COVID-19: A Systematic Review

Baricitinib is an oral selective Janus kinase 1 and 2 inhibitor with known anti-inflammatory and anti-viral properties. In patients hospitalized for coronavirus disease 2019 (COVID-19), baricitinib has shown to reduce the risk of death in line with dexamethasone and tocilizumab. However, the most effective and safe dose or optimal dose of baricitinib in severe COVID-19 was not addressed. We conducted this systematic review to assess whether higher than usual dose could further improve survival as primary outcome. The need of ICU (Intensive care Unit) and Invasive or non-invasive positive pressure ventilation, time to wean from oxygen, length of stay at hospital and adverse events were analyzed as secondary outcome. We included 10,032 patients in 5 studies (2 randomised control trials and 3 high quality clinical trials). Among them,5,071 patients received baricitinib at different dosage (4909 patients received 4 mg once daily and 162 patients got more than 4 mg daily) and 4961 received standard of care. Baseline characteristics including mean age, sex, co-morbidities, inflammatory marker (C-reactive protein/CRP) were similar across the intervention and standard care groups. 4 out of 5 trials showed significant survival benefit in baricitinib group usual to higher dose (4 to 8 mg daily). Use of higher dose in 3 controlled trials was associated with significant reduction in admission to ICU and requirement of invasive or non-invasive ventilation support, shortening of hospital stay and earlier stabilization of oxygen status which was not evident in two randomized control trials using usual dose (4 mg daily). There was no significant difference in any serious adverse events or opportunistic infections between higher dose versus usual dose group. Therefore, baricitinib in higher dose could be a potent, highly effective and safe immunomodulatory drug in hospitalized patients with severe COVID-19.