Impact of Timing of Tocilizumab Use in Hospitalized Patients With SARS-CoV-2 Infection

Abstract

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to be a global challenge due to the lack of definitive treatment strategies. We sought to determine the efficacy of early administration of anti-interleukin 6 therapy in reducing hospital mortality and progression to mechanical ventilation. METHODS: This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of >88%. The Charlson comorbidity index was used as an objective assessment of the burden of comorbidities to predict 10-year mortality. The primary outcome of interest was hospital mortality. Secondary outcomes were progression to mechanical ventilation; the prevalence of venous thromboembolism and renal failure; and the change in C-reactive protein, D-dimer, and ferritin levels after tocilizumab administration. Propensity score matching by using a 1:2 protocol was used to match the tocilizumab and non-tocilizumab groups to minimize selection bias. The groups were matched on baseline demographic characteristics, including age, sex, and body mass index; Charlson comorbidity index score; laboratory markers, including ferritin, D-dimer, lactate dehydrogenase, and C-reactive protein values; and the maximum oxygen requirement at the time of tocilizumab administration. Mortality outcomes were evaluated based on the level of oxygen requirement and the day of hospitalization at the time of tocilizumab administration. RESULTS: The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P 5 .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator. CONCLUSIONS: Early use of anti-interleukin 6 therapy may be associated with improved hospital mortality and reduction in progression to more severe coronavirus disease 2019.

Infectious complications after tocilizumab in patients with COVID: a real-world experience

“…Several studies are able to identify a potential relationship between lower mortality and early use of tocilizumab, although the definition of “early” varies (for example, within 24 h after hospital admission in 17 , within 12 days of symptom onset in 18 , or at the inflammatory stage in 19 ). One particular study in Northwell Health System enrolling more than 11,000 patients 20 showed there was a consistent suggestion of a trend of increasing mortality with each day’s delay in tocilizumab administration at all level of oxygen requirements.…”

Tocilizumab for Treatment of Children and Young Adults With Severe Acute COVID-19: Experience at a Quaternary-care Children’s Hospital

“…Adult studies have similarly reported that early administration of tocilizumab was associated with improved outcomes in adults with COVID-19 disease. 5,8,9 In these studies, factors related to severity of illness including mechanical ventilation at time of tocilizumab administration and treatment later during hospitalization were associated with poorer outcomes. These findings support the National Institutes of Health's recommendation for using tocilizumab with steroids within 24 hours of admission to the intensive care unit.…”

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis

“…Moreover, study methodology varied widely regarding both use of biomarkers as inclusion criteria and timing, indication and dose of re-injection, with restrospective data suggesting a variable treatment effect according to disease severity, timing and dosage of treatment. 11,12 Whether identifying a subset of responders, optimal timing or need for higher doses or re-injection would impact survival remains an important unresolved question.…”

“…Retrospective work has suggested that treatment response is variable depending both on illness severity but also on treatment modalities. 11,12 Fine tuning the subset of patients most likely to benefit from such therapies as well as the ideal timing of administration and dosage can only be achieved by a better understanding of their effect on the immune response.…”