Does timing of tocilizumab administration affect mortality in COVID-19? A Scottish multicentre retrospective cohort study.

Background: The optimal timing of tocilizumab treatment during the disease course of COVID-19 has yet to be adequately defined in the context of randomised controlled trials and the effect of tocilizumab on real-world populations remains unclear. We examined the effect of different timing of tocilizumab, on mortality, in a cohort of adults with COVID-19.

Methods: All adults (≥18 years old) with confirmed COVID-19 admitted to four hospitals in the West of Scotland between 8 January 2021 and 31 March 2021 and who received tocilizumab were included in a retrospective observational cohort study. Patients were assigned to either an early (day of admission or first day after admission) or late (days 2-7 of admission) cohort based on tocilizumab initiation. The primary outcome was 90-day all-cause mortality in early versus late cohorts. Secondary outcomes were 28 and 180-day all-cause mortality.

Results: 203 patients were included in the analysis (138 in the early cohort, 65 in the late cohort). Mortality in 90 days in the early cohort was 22% (n=30) compared with 45% (n=29) in the late cohort (p<0.001). The adjusted mortality was significantly higher in the late cohort compared with the early cohort (adjusted OR: 3.33; 95% CI: 1.29 to 8.54; p=0.012). The secondary outcomes demonstrated the same effect with higher rates of death in 28 days (late cohort adjusted OR: 3.28; 95% CI: 1.23 to 8.75; p=0.018) and 180 days (late cohort adjusted OR: 3.70; 95% CI: 1.45 to 9.45; p=0.006). The effect was seen whether the outcome was adjusted or unadjusted.

Conclusion: Early administration of tocilizumab within the first 2 days of hospitalisation was associated with a significant survival benefit compared with late exposure. Late administration was associated with particularly high mortality. The observed association may be a result of residual confounders and further research is needed.