Low-Dose Versus High-Dose Tocilizumab in Covid-19 Patients with Hypoxic Respiratory Failure

ABSTRACT

INTRODUCTION: Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19. Tocilizumab dose of 8 mg/kg (max 800 mg), stemmed from the RECOVERY trial, has been the standard dose for COVID. Due to a drug shortage of tocilizumab, our study seeks to assess whether low dose (400 mg) shows similar benefit compared to high dose for COVID patients concurrently on same median dose of steroids. METHOD(S) This was a retrospective observational study of COVID-19 patients who received tocilizumab in conjunction with steroids. Between March 2020 and August 2021, adult patients with positive COVID-19 PCR, hypoxic respiratory failure defined as FiO2>70%, and received a dose of tocilizumab in conjunction with steroids were included. Patients were excluded if they have died within 24 hours of treatment initiation. Primary outcome was 28-day mortality and secondary outcomes included biomarker improvement and relative risk of infection. Propensity matched analysis between groups was performed. RESULT(S) A total of 407 patients met the study criteria and were analyzed. The low dose and high dose tocilizumab group had 222 and 185 patients respectively. Gender and age were similar between groups and all patients received steroids. The low dose group was significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis of 56 patients in each group, with a median dose of steroid of 10 mg in both groups showed no difference in 28 day mortality (HR 0.82 [95% CI 0.41-1.67];p=0.6138). A greater decrease to normalization of CRP (p< 0.0001) and downtrend of ferritin (p=0.503) was observed in the high dose group at day 14. The high dose group trended a higher rate of fungal and viral infections. CONCLUSION(S) Compared to low dose tocilizumab, high dose did not provide additional efficacy and mortality benefit but resulted in uptrend of fungal and viral infections. While a greater decrease in CRP was seen in the high dose group, it did not translate into lower mortality. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.