(133) The Comparative Effectiveness of Baricitinib And Tocilizumab in Hospitalized Patients With Covid: A Retrospective Cohort Study of The National Covid Cohort Collaborative (N3C)

Background: Real-world studies comparing baricitinib and tocilizumab for the treatment of COVID-19 have been constrained by small sample sizes, included patients from a limited number of sites, and have yielded conflicting results.

Objectives: To compare the effectiveness of baricitinib versus tocilizumab on mortality and clinical outcomes among hospitalized patients with COVID-19 in the United States.

Methods: We emulated a target trial to compare the effectiveness of baricitinib versus tocilizumab using data from the National COVID Cohort Collaborative (N3C), the largest electronic health records repository of individuals in the U.S. We included adults hospitalized for COVID-19 between February 2020 and October 2023 who newly initiated baricitinib or tocilizumab within 3 days of hospitalization. Our primary outcome was 28-mortality and secondary outcomes included in-hospital mortality, hospital-acquired infections, intensive care unit (ICU) length of stay, and hospital length of stay. We calculated inverse probability of treatment weights (IPTW) using sociodemographic characteristics, respiratory support, comorbidities and vaccination status, and then conducted logistic regression or negative binomial models depending upon outcome.

Results: Among 11,157 patients included in the study, 6,485 received baricitinib and 4,672 tocilizumab. Overall, the mean age of the cohort was 59.9±15.1 years, 6,720 (60.2%) were male, 1,346 (12.1%) were admitted to the ICU, and 2,149 (19.3%) received invasive mechanical ventilation. All baseline covariates were balanced across two exposure groups after IPTW. In the IPTW analysis, compared to tocilizumab use, baricitinib use was associated with lower 28-day mortality (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.86–0.98), and hospital mortality (OR 0.86, CI 0.81–0.91). Baricitinib was also associated with shorter hospital length of stay (incident rate ratio [IRR] 0.89, CI 0.87–0.91) and lower rates of hospital-acquired infections (OR 0.73, CI 0.65–0.81). No difference was noted for ICU length of stay between the two groups.

Conclusions: Among hospitalized adults with COVID-19, baricitinib was associated with improved 28-day mortality and other clinical outcomes compared to tocilizumab. We cannot rule out the possibility for residual confounding in this real-world study.