Do Bruton Tyrosine Kinase Inhibitors Improve Outcomes for SARS-CoV-2?

A small-scale evidence review found that use of Bruton tyrosine kinase inhibitors (BTKIs) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was associated with decreased oxygen requirements and decreased hospitalization rates and duration. Findings of the review were recently published in Clinical Immunology.

Patients infected with SARS-CoV-2 have an elevation of certain immune biomarkers associated with activation of the innate immune system, such as BTK, making it a potential target for treatment of COVID-19. While the clinical data have yet to prove this, it has been hypothesized that inhibiting BTK will improve lung injury in patients with severe COVID-19.

Researchers from the National Institutes of Health (NIH) conducted a systematic review to describe clinical outcomes measured from use of BTKIs during acute SARS-CoV-2 infection. They searched PubMed, Embase, and Web of Science:Core on December 30, 2020, to identify clinical studies with at least five COVID-19 patients treated with BTKIs. A total of 125 articles were identified, with 6 meeting the inclusion criteria.

The most common clinical outcomes measured in these studies were oxygen requirements (4/6) and hospitalization rate or duration (3/6). In patients who started or continued BTKIs, 3 studies demonstrated decreased oxygen requirements and favorable outcomes regarding hospitalization rate and duration. Notably, these studies did not currently identify use of BTKIs to be associated with improved overall survival.

The authors concluded, “While the available data are not currently robust enough to recommend BTKIs on a clinical basis for the treatment of acute SARS-CoV-2 infection, they do provide a framework to assess specific and longitudinal clinical outcomes associated with uncontrolled inflammation in COVID-19.”

“The completion and reporting of randomized clinical trials of various [BTKIs] in patients with COVID-19 will help elucidate the precise role of these targeted drugs in the management of these patients,” they added.

Reference

Stack M, Sacco K, Castagnoli R, Livinski AA, Notarangelo LD, Lionakis MS. BTK inhibitors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A systematic review. Clin Immunol. Published online August 2, 2021. doi:https://doi.org/10.1016/j.clim.2021.108816