Real World Long-term Assessment of The Efficacy of Tocilizumab in Patients with COVID-19: Results From A Large De-identified Multicenter Electronic Health Record Dataset in the United States

Abstract

Background : Studies have shown conflicting results on the efficacy of tocilizumab (TCZ) for patients with COVID-19, with many confounders of clinical status and limited duration of the observation. Here, we evaluate the real-world long-term efficacy of TCZ in COVID-19 patients. Methods : We conducted a retrospective study of hospitalized adult patients with COVID-19 using a large US-based multicenter COVID-19 database (Cerner Real-World Data; updated in September, 2020). The TCZ group was defined as patients who received at least one dose of the drug. Matching weight (MW) and a propensity score weighting method were used to balance confounding factors. Results : A total of 20,399 patients were identified. 1,510 and 18,899 were in the TCZ and control groups, respectively. After MW adjustment, no statistically significant differences in all-cause mortality were found for the TCZ vs. control group (Hazard Ratio [HR]:0.76, p=0.06). Survival curves suggested a better trend in short-term observation, driven from a subgroup of patients requiring oxygen masks, BIPAP or CPAP. Conclusion: We observed a temporal (early) benefit of TCZ, especially in patients on non-invasive high-flow supplemental oxygen. However, the benefit effects faded with longer observation. The long-term benefits and risks of TCZ should be carefully evaluated with follow-up studies.

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France

“…One striking finding of this study was that early administration of tocilizumab (within 48 h following hospital admission) was associated with a better outcome. This result was in accordance with those reported in other studies suggesting the benefit of tocilizumab administration within 2-3 days of hospital admission [8,10,11]. Similarly, the results of the sensitivity analyses of RECOVERY trials [5] have also suggested that patients who received tocilizumab within seven days of symptom onset are those who benefited the most.…”

“…Other studies [7,8,10,11,19], including platform trials [5,6], have reported a favorable effect of tocilizumab in alpha, beta or gamma cases; however, the benefit of tocilizumab in patients infected with delta, which is reported to be more virulent [20], or in patients infected with omicron, which is, in contrast, reputed to be less virulent [21], remained disputable. To the best of our knowledge, this study was the first to report the use of tocilizumab in a large cohort of severe COVID-19 patients infected with the delta and omicron VOC, suggesting that, among the patients developing a severe form of the disease, the mortality rates were similar in the omicron and delta cases, as it has been reported with previous VOCs [14].…”

“…In mid-2021, two large platform trials reported that tocilizumab reduced mortality and the use of invasive mechanical ventilation, and increased the chances of a successful hospital discharge [5,6]. Subsequently, numerous studies have investigated its effect in patients with SARS-CoV-2 pneumonia caused by the alpha, beta or gamma variants of concern (VOC) [7][8][9][10][11], even recently reporting that the antagonist of IL-6 receptors also improved long-term outcomes [12]. Unfortunately, in numerous countries, several factors have limited the use of tocilizumab, such as drug shortages, high cost or late approval (December 2021 in Europe, December 2022 in the USA).…”

Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: a subgroup analysis of the SAVE-MORE randomised trial

“…However, the benefit of treatment faded over time, while long-term adverse events, especially superinfections, were worrisome. 15 , 16 Baseline levels of circulating ferritin and aspartate aminotransferase (AST) were higher among 90-day non-survivors. Ferritin and AST are among the traits of cytokine storm of COVID-19, which is a well-recognised driver of death in COVID-19.…”