Tocilizumab Could Treat Cytokine Release Syndrome in Severe COVID-19 Patients

Biologic therapy tocilizumab is associated with improved inflammatory markers, as well as better respiratory and hemodynamic outcomes in treated patients requiring mechanical ventilation due to severe COVID-19 infection.

According to new retrospective data presented at the Making A Difference in Infectious Disease (MAD-ID) 2021 Annual Meeting this week, a team of Florida-based investigators reported that interleukin 6 (IL-6) targeting monoclonal antibody tocilizumab provided noted benefit for reduced symptoms of cytokine release syndrome (CRS) associated with severe COVID-19.

The findings, presented by Amy L. Carr, PharmD, of AdventHealth Medical Group in Orlando, provide rationale for the further assessment of tocilizumab for the difficult and multifactorial syndrome associated with COVID-19.

As Carr and colleagues noted, tocilizumab has been evidenced in major COVID-19 clinical trials RECOVERY and REMAP-CAP to be a viable agent in treating severely ill, hospitalized patients with COVID-19 whose symptoms include worsening respiratory status and significant inflammation.

However, the agent’s use in treated CRS, and the inflammatory and clinical markers associated with the condition, have not been observed.

The team conducted a retrospective study of severely ill COVID-19 patients who required mechanical ventilation, treated with tocilizumab between March and April 2020 at a large community teaching hospital. Tocilizumab dosing was 400 mg, delivered intravenously to indicated patients.

Carr and colleagues included the first 25 patients with COVID-19 who were treated with 400 mg tocilizumab for their analysis. Just 5 (20%) of patients received second dose of therapy.

An observation of inflammatory marker trends 7 days after treatment showed increased in free IL-6, as well as initial “rapid increases” in d-dimer levels. Levels steadily declined thereafter. Investigators additionally observed consistent reductions in c-reactive protein (CRP), ferritin, and procalcitonin in treated patients.

Patients showed improvement at 3 days post-tocilizumab administration by a series of clinical metrics: fever resolution, decreased requirement of vasopressor, and improved oxygenation per PaO2:FiO2.

The investigators concluded that the decreased inflammatory markers, as well as bettered respiratory and hemodynamic levels indicated an improvement of severe COVID-19 status in patients treated with tocilizumab.

“Reductions in CRP may be useful as a surrogate marker to trend improvement in cytokine storm,” they wrote. “Analysis of ongoing and future, comparative, randomized studies will be needed to assess the safety and efficacy of this approach to SARS- CoV-2 associated CRS.”