Baricitinib

partially relieved cytokine storm syndrome

rapid reduction in oxygen flow need

Baricitinib blocks JAK/STAT mediated signalling in primary liver spheroids. This route of signalling could be linked to sensitization of human liver cultures to SARS-CoV-2 infection. Baricitinib also inhibits the host numb associated kinases and efficiently blocks viral entry in vitro. A significantly lower portion of patients treated with baricitinib reached the primary endpoint compared to a matched control cohort. Positive effects were observed early in the treatment course. Baricitinib was generally well tolerated, although adverse effects (e. g. transaminitis or infections) were observed. Sample size: 83 + 83 matched control. Dosage: 4 mg daily for 14 days. Endpoint: The composite of death or invasive mechanical ventilation (primary).

Despite not limiting SARS-CoV-2 replication in rhesus macaques, baricitinib was well-tolerated, had positive pharmatokinetic properties, reduced inflammation (observed at molecular, biochemical, and histological levels) and lung damage.

Patients who received baricitinib in addition to remdesivir displayed faster clinical recovery, compared to those who received only remdesivir combined with placebo. Baricitinib use was not associated with a significantly higher incidence of adverse events. Sample size: (Intention-to-treat) 515 + 518 placebo. Dosage: 4 mg daily for 14 days or until hospital discharge. Main outcome: Time to recovery.

Combined with

The treatment in combination with remdesivir was effective in blocking cytokine storm in a 35 years old (otherwise healthy) COVID-19 patient. Fast pulmonary and retarded CNS recovery was observed afterwards. Sample size: 1. Dosage: 4 mg daily for 5 days.

The compound was shown to suppress interferon signalling-sensing enhancers in the ACE2 locus in vitro. This was hypothesized to contribute to its therapeutic effect in COVID-19 treatment. 

SARS-CoV-2 (WT/alpha/beta/delta variant) Spike protein’s N-terminal domain induced inflammation in an in vitro model. This inflammation was partially inhibited by the compound. 

The treated patients displayed a reduction in IL-6, IL-1β, and TNF-α, recovery in circulating T and B cell levels, increased anti-Spike antibody secretion. It was associated with an improvement in oxygenation. Sample size: 20 + 56 control. Dosage: 4 mg twice daily on days 1 and 2, once daily on days 3–9 (the dosing was halved in patients of 75+ years of age). Main outcome: Mortality, ARDS incidence, and the duration of hospitalization.

Baricitinib combined with hydroxychloroquine was temporally associated with clinical improvement in 11 of 15 patients. Causal association could not be established, however. Sample size: 15. Dosage: 2–4 mg daily. 

The treatment was safe. The clinical status of the treated patients was improved at 2 weeks and no ICU admission was required in this cohort. Sample size: 12 + 12 control. Dosage: 4 mg daily. 

The treatment was safe. It reduced mortality, lowered ICU admission rate in pneumonia patients and reduced nasopharyngeal viral burden. Sample size: 113 + 78 control. Dosage: 4 mg daily. Main outcome: Mortality rate.

Clinical improvement was observed in a patient without a sufficient response to an antiretroviral therapy, hydroxychloroquine and anti- IL-6 therapy after baricitinib treatment. Sample size: 1. Dosage: 4 mg daily for 2 weeks. 

The compound reduced immune response of whole-blood samples to stimulation of SARS-CoV-2 peptides (predicted and synthetized). Its efficacy was observed especially in the samples from patients with mild to moderate COVID-19 

A higher loading dose (of 8 mg) was observed to produce some superior clinical outcomes compared to the standard regimen. Sample size: 20 (higher loadind dose) + 17 (standard dosing control). Dosage: 4 mg daily for 14 days with or without a higher (8 mg) loading dose. 

The treatment was considered safe and an associated clinical improvement was observed. Sample size: 43. Dosage: 4 mg daily for 5–7 days. Main outcome: Clinical improvement on an ordinal scale at day 15 of the treatment.

Combined with dexamethasone and remdesivir, the treatment mostly led to a favourable clinical outcome. Sample size: 45. Dosage: 4 mg or 2 mg or 1 mg daily (based on glomerular filtration rate) for 7 days or until hospital discharge (mean 6 days). Main outcome: Hospitalization length, shock presence, and thrombosis occurrence.

The use of baricitinib on top of corticosteroids was associated with better clinical outcome compared to corticosteroid treatment only. The daily dose of 4 mg seemed to be more efficient than the one of 2 mg daily. Sample size: 62 + 50 control. Dosage: 4 mg daily for 5 to 10 days or 4 mg on day one and then 2 mg daily. Main outcome: The change in SpO2/FiO2 from hospitalization to discharge.

Gradual clinical improvement was observed after baricitinib therapy initiation in an immunosuppressed cancer patient who was not responding to methylprednisolone, remdesivir and heparin treatment. Sample size: 1. Dosage: 4 mg daily. 

The use of baricitinib was associated with decreased mortality in severe COVID-19 patients. Sample size: 193 + 176 control. Dosage: 4 mg daily for 14 days or until hospital discharge. Main outcome: ICU admission/death composite.

Rapid clinical improvement leading to hospital discharge was observed after treatment initiation in an obese 17-year-old female patient. Sample size: 1. Dosage: 4 mg daily for 5 days. 

Addition of baricitinib on top of the dexamethasone treatment resulted in statistically significant decrease in mortality in COVID-19 pneumonia patients. No significant difference in progression to invasive mechanical ventilation or hospital acquired infections rates was observed. Sample size: 123 + 74 dexamethasone only. Main outcome: 30-day mortality.

Early high dose of baricitinib was associated with clinical improvement and better outcomes. Sample size: 122 high dose + 116 low dose. Dosage: 14 days of 8 mg daily (high dose group) or 4 mg daily (low dose group). 

The 30-day mortality among the treated patients aged 70 or older was statistically significantly lower compared to the control. The difference within the cumulative cohort (both below and equal to or above 70 years of age) was not statistically significantly different, however. Sample size: 86 (<70 years old) + 78 (≥70 years old) + 86 control (<70 years old) + 78 control (≥70 years old). Dosage: Average total of 20.6 mg (<70 years old) or 14.3 mg (≥70 years old). Main outcome: 30-day mortality.

The combination of baricitinib, remdesivir and dexamethasone seemed to generally lead to improved survival in hospitalized COVID-19 patients. Sample size: 27 yes + 73 no. Dosage: 4 mg daily for 14 days or until hospital discharge or death (renal function-based dose adjustment in 26% of patients). 

The combination of baricitinib, remdesivir and dexamethasone seemed to generally lead to positive clinical outcomes in the treatment of severe COVID-19 patients. There was no control group, however. Sample size: 44. Dosage: 4 mg daily for 14 days or until hospital discharge. 

Human- and AI-powered data mining led the authors to a conclusion that baricitinib is a good candidate drug for COVID-19 treatment. 

Baricitinib inhibited human numb-associated kinases, which also led to reduced viral infectivity in vitro. In a case series, clinical improvement and viral load reduction were observed. Sample size: 4 patients. Dosage: 2 to 4 mg daily for 10 to 12 days. 

A 46% relative reduction in 28-day mortality (statistically significant) was observed in the treatment group compared to placebo. Sample size: 51 + 50 placebo. Dosage: 4 mg daily for up to 14 days. 

A 38.2% relative reduction in mortality (statistically significant) was observed in the treatment group compared to placebo. Overall disease progression frequency was not significantly reduced, however. Sample size: 764 + 761. Dosage: 4 mg daily for 14 days. Main outcome: Progression to high-flow oxygen, mechanical ventilation or death by the day 28 composite.