Tocilizumab Treatment in Severe to Critical Coronavirus Disease 2019 (COVID-19) Patients

Abstract

Rationale. In the Philippines, Tocilizumab is an investigational drug and our guidelines had allowed its use in severe to critical patients with SARS-CoV-2. Tocilizumab was often given during or after intubation when the cytokine surge has already occurred. We hypothesized that the timing of administration of Tocilizumab may also affect its effectiveness as a treatment. Methods. We conducted a retrospective observational study of all patients admitted in our intensive care unit from March 1 to August 30, 2020 analyzing the effect of its timing relative to intubation (“early” or given prior to intubation or noninvasive ventilation vs “late” or given on the day or after) on 28-day mortality and survival post-intubation. Results. Ninety severe to critically ill patients were admitted at the ICU. The baseline characteristics are shown in Table 1. Tocilizumab was given to 68 (76%) and their mortality rate was 47.06% (n=32). This was comparable to the 54.54% (12/22) mortality rate of the patients not given Tocilizumab, (p=0.541). Both groups received similar standard of care, including the use of Dexamethasone, which was started in June, after the release of the Randomized Evaluation of COVID 19 Therapy (RECOVERY) trial results. Of the 68 patients who received Tocilizumab, 27 (30.7%) received the drug “early' with a mean day (±SD) of 3.96 ±3.46 prior to intubation or noninvasive ventilation while 41 received it “late” with a mean day (±SD) of 0.762 ± 3.18. The 28-day mortality in the early group was 29.63% (8/27) which was significantly lower than the 58.54%, (24/41) in the late group (p=0.019). Their mean days of survival post intubation was significantly better for the early group (26.21 vs. 19.56;p=0.0008). The hazards ratios (after adjusting for covariates) for early Tocilizumab alone is 0.2744268 (95% confidence interval, 0.0842749 to 0.8936242, p=0.032) while that of both Dexamethasone and Tocilizumab use is 0.3387582 (95% ci: 0.1327466 to 0.8644829, p=0.024). Conclusion. Tocilizumab may potentially ameliorate the inflammatory response as has been shown by early data and this may potentially prevent intubation. Our data is inherently limited by its retrospective nature but it shows that late administration of Tocilizumab after the cytokine storm when respiratory failure has ensued may be detrimental to patients. Our hazards ratios using Cox multiple regression did show that giving Tocilizumab to severely ill patients prior to respiratory failure may improve survival.