Tocilizumab may reduce mortality in COVID-19 patients at risk of CRS

Tocilizumab (TCZ) therapy appears to be effective in patients at risk of cytokine release syndrome (CRS) from the novel coronavirus disease (COVID-19), suggests a study presented at ID Week 2020. Those receiving TCZ in a nonintensive care unit (non-ICU) setting show better response than ICU patients.

In addition, ICU admission, obesity, and acute kidney injury (AKI) are associated with high rates of mortality, but there is no statistical difference in early vs late therapy, according to the researchers.

This retrospective study was conducted to investigate treatment responses of critical based TCZ therapy for SARS-CoV-2 respiratory infection for ICU vs non-ICU patients. Institutional criteria were established to identify those at risk of CRS from COVID-19. Patients were included if they were ≥18 years old, were admitted for at least 72 hours, and received at least 1 dose of TCZ.

Clinical improvement (CI) at the end of admission was the primary endpoint. CI was defined by extubation, downgrade from ICU, discharge, or improvement in Clinical Ordinal Scale by 2. Secondary endpoints included inpatient mortality (IM) and risk factors associated with IM. Finally, impact of early (<96 hours) vs late (>96 hours) TCZ therapy on IM was included in subgroup analysis.

A total of 170 patients (87 ICU and 83 non-ICU) met the eligibility criteria and received TCZ therapy between 25 March and 6 May 2020. Forty-five patients required invasive mechanical ventilation (IMV). In addition, patients in the ICU were more likely to be obese, receive two doses of TCZ, and have longer length of stay. [ID Week 2020, abstract 550]

Seventy-one percent of patients achieved overall CI, which appeared to be higher in non-ICU than ICU patients (85.5 percent vs 57.5 percent; p=0.002). Overall IM stood at 18.8 percent, but it was substantially lower in non-ICU than ICU patients (8.4 percent vs 28.7 percent; p=0.0014). IM was also higher in those on IMV vs non-IMV (30 percent vs 15.4 percent; p=0.03).

AKI, body mass index ≥30 kg/m², and risk factors for ICU admission correlated with higher IM risk. IM did not differ between patients receiving early vs late TCZ therapy; however, a trend toward lower mortality was observed with early TCZ.

“We didn’t evaluate the rates of super infections noted after TCZ therapy,” the researchers said. “[H]owever, [the] most common side effect of therapy was transaminitis, [which occurred] in 21 percent of patients.”

Furthermore, a recent observational study found a beneficial effect of TCZ therapy among COVID-19 patients requiring ICU support. An association was observed between TCZ administration and lower hospital-related mortality (hazard ratio, 0.64, 95 percent confidence interval, 0.47–0.87; p=0.0040). Similar associations were seen among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of ≥15 mg/dL. [Lancet Rheumatol 2020;2:E603-E612]

Notably, the current study had no comparison group since it was not a clinical trial, but a study with a controlled comparison group would provide more insight into the “most appropriate place in therapy for TCZ for COVID-19,” the researchers said.

A monoclonal antibody against the interleuikin-6 receptor, TCZ is believed to be beneficial in COVID-19–induced CRS.