Disease progression in COVID-19 is associated with an impaired immune response, which leads to a cytokine release syndrome, or hyperinflammatory state.1 Treatment or management of this response could improve disease outcomes and mortality risk – this can be achieved by using steroidal drugs, such as dexamethasone, which is already used for COVID treatment in countries including the United Kingdom and United States.2,3
Recent studies propose that Janus kinase (JAK) inhibitors, traditionally used for the treatment of rheumatoid arthritis, also show potential in combatting the hyperinflammatory phase in COVID-19.1,2 A meta-analysis of five clinical studies and six cohort studies highlights that JAK inhibitors, ruxolitinib and baricitinib, have shown some evidence of improving survival, reducing the need for invasive mechanical ventilation, and reducing the need for transfer to intensive care, although the length of hospitalisation remained similar.1
A recent study brings to the table another JAK inhibitor, tofacitinib, with possible treatment benefit in patients hospitalised with COVID-19 pneumonia. The study involved 289 patients across 15 sites in Brazil, and about 89% of the patients received glucocorticoids during hospitalisation. Patients were either treated with 10 mg tofacitinib or placebo twice a day for up to 14 days or until they were discharged. Key findings from the study are highlighted below4:
The results indicate that tofacitinib is relatively safe compared to placebo and could reduce the risk of mortality and respiratory failure in patients hospitalised with COVID-19, but hospital durations and ICU stay remained similar.
Timing of JAK inhibitor use in the treatment of COVID-19 might also be important, but mixed reports and inconsistencies in these data make it difficult to draw clear conclusions.1 Furthermore, there has been evidence that advanced disease in COVID-19 leads to a hypercoagulable state.5 JAK inhibitors have been known to carry a risk of thrombosis, and this risk may be increased in these hypercoagulable phases of disease.5 This, and other possible side effects remain key concerns, but the data from this study provides further evidence on the use of JAK inhibitors in the treatment of severe COVID-19, and will better inform future treatment guidelines.