Comparative associations of Anakinra and Tocilizumab initiation with in-hospital mortality in severe COVID-19: A single-center sequential cohort study.

BACKGROUND: Interleukin-1 and interleukin-6 blockade have been widely used in severe COVID-19, but comparative real-world evidence regarding anakinra and tocilizumab in critically ill patients remains limited. We evaluated the associations of first initiation of anakinra or tocilizumab with 28-day and overall in-hospital mortality. METHODS: This single-center retrospective ICU cohort included adults with severe COVID-19. During hospital days 2-10, daily actions were classified as anakinra initiation, tocilizumab initiation, or control/defer. Calibrated overlap-weighted modified-Poisson models estimated associations with 28-day and overall in-hospital mortality; ferritin-adjusted sensitivity analyses were performed. RESULTS: Of 306 patients, 241 patients contributed 1,297 eligible person-days. Calibration met the prespecified balance criterion for the included covariates, although effective support for tocilizumab initiation remained limited. For 28-day in-hospital mortality, adjusted RRs versus control/defer were 0.99 (95% CI, 0.80-1.22) for anakinra and 0.99 (95% CI, 0.71-1.37) for tocilizumab. No clear associations were identified in the head-to-head comparison or for overall in-hospital mortality; ferritin-adjusted estimates were similar. CONCLUSIONS: In this retrospective ICU cohort, neither anakinra nor tocilizumab initiation showed a clear association with 28-day or overall in-hospital mortality. Estimates were imprecise, particularly for tocilizumab, and remain susceptible to residual confounding.