(1198) Effects of Fixed Dose Versus Weight-Based Tocilizumab on Escalation of Oxygen Support in SARS-CoV-2

Introduction: Tocilizumab has demonstrated benefit in managing severe COVID-19 at 8 mg/kg doses. However, a nationwide drug shortage in 2021 led to a shift in dosing protocol to a fixed 400 mg dose at this institution. This study aimed to evaluate whether fixed-dose tocilizumab is non-inferior to weight-based dosing regarding escalation of oxygen support in patients with COVID-19.

Methods: This retrospective, single center, cohort chart review analyzed data from hospitalized COVID-19 patients between March 2020 and August 2022. Adult patients who received one dose of IV tocilizumab for rapidly deteriorating respiratory status with confirmed or suspected COVID-19 infection were included.

Patients who received tocilizumab before August 13, 2021 were assigned the 8 mg/kg weight-based group (n = 121). Patients weighing above 62.5 kg who received tocilizumab on or after August 13, 2021 were included in the 400 mg fixed-dose group (n = 363). Patients weighing 62.5 kg or less were included in the weight-based group regardless of administration date.

The primary non-inferiority analysis evaluated need for oxygen therapy escalation within 48 hours of tocilizumab administration using change from baseline on an ordinal scale. Patients who experienced any escalation on the scale during this time frame were considered to have experienced the primary endpoint. Secondary endpoints included degree of oxygen escalation, rate of mechanical ventilation at seven days, ICU length of stay, 28-day mortality, bowel perforation incidence, and rate of new or suspected secondary infections.

Results: The primary outcome of the need for oxygen escalation occurred in 33 (27.3%) patients in the weight-based group and 114 (31.4%) in the fixed-dose group (𝛸2 = 0.734; df = 1; 97.5% CI, -0.051 to 1; p = 0.196). There were no statistical significant differences in secondary outcomes of seven-day mechanical ventilation rates, ICU length of stay, 28-day mortality, bowel perforation rates, or secondary infection rates.

Conclusions: A single fixed 400 mg dose of tocilizumab was non-inferior to 8 mg/kg weight-based dosing in preventing escalation of oxygen support within 48 hours for patients with severe COVID-19. Fixed dose 400 mg tocilizumab can be considered as an alternative to weight-based dosing without compromising efficacy.