Tocilizumab for the treatment of COVID-19 among hospitalized patients: A matched retrospective cohort analysis

Ignatius, Elisa H; Wang, Kunbo; Karaba, Andrew; Robinson, Matthew; Avery, Robin K; Blair, Paul; Chida, Natasha; Jain, Tania; Petty, Brent G; Siddiqui, Zishan; Melia, Michael T; Auwaerter, Paul G; Xu, Yanxun; Garibaldi, Brian T

BACKGROUND: There is currently no single treatment that mitigates all harms caused by SARS-CoV-2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as adjunctive immune-modulating therapy. METHODS: This was an observational, retrospective study of hospitalized adult patients with confirmed COVID-19. The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. Time-dependent propensity score matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections. RESULTS: This analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (aHR 0.38, 95% CI: 0.21-0.70) and no change in time to clinical improvement (aHR: 1.13, 95% CI: 0.68-1.87). The 1:1 matched dataset also showed a lower mortality rate (27.8% vs. 34.4%) and reduced hazards of death (aHR: 0.47, 95% CI: 0.25-0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared to controls. Secondary infection rates were similar between the two groups. CONCLUSIONS: Tocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection.