Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case–controlled study

Abstract

Summary Background COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. Aims To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. Methods We conducted a retrospective, case–control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. Results A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). Conclusion Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality.

Immunosuppressive Drugs and COVID-19: A Review

“…In four other studies, the mortality and ICU admission rate were not significantly different between patients treated with an IL-6-inhibitor (tocilizumab or sarilumab) and controls ( Campochiaro et al., 2020 ; Colaneri et al., 2020 ; Della-Torre et al., 2020 ; Rojas-Marte et al., 2020 ). Similarly, the discharge rate ( Campochiaro et al., 2020 ), duration of hospitalization ( Campochiaro et al., 2020 ), blood stream infections ( Giacobbe et al., 2020 ), serious adverse event rate (including infections and bacteremia) ( Campochiaro et al., 2020 ) and rate of clinical improvement after 28 days ( Della-Torre et al., 2020 ) were not significantly different.…”

“…Patients with severe COVID-19 have high levels of IL-6 ( Mosharmovahed et al., 2020 ) and in three cohort studies, tocilizumab use was associated with lower mortality and ICU admission rate ( Capra et al., 2020 ; Klopfenstein et al., 2020 ; Moreno-García et al., 2020 ). However, other cohort studies report contradictory results ( Campochiaro et al., 2020 ; Colaneri et al., 2020 ; Della-Torre et al., 2020 ; Giacobbe et al., 2020 ; Quartuccio et al., 2020 ; Rojas-Marte et al., 2020 ). Furthermore, the risk of confounding in these observational studies is high.…”

“…Similarly, the discharge rate ( Campochiaro et al., 2020 ), duration of hospitalization ( Campochiaro et al., 2020 ), blood stream infections ( Giacobbe et al., 2020 ), serious adverse event rate (including infections and bacteremia) ( Campochiaro et al., 2020 ) and rate of clinical improvement after 28 days ( Della-Torre et al., 2020 ) were not significantly different. In three of these studies ( Colaneri et al., 2020 ; Della-Torre et al., 2020 ; Rojas-Marte et al., 2020 ), the controls were matched to the tocilizumab-treated patients on several important patient characteristics in order to reduce the risk of confounding by indication. In the fourth study ( Campochiaro et al., 2020 ), the patient characteristics and disease severity at admission were not significantly different between both groups and the eligibility criteria for tocilizumab were clearly defined.…”

Efficacy and safety of tocilizumab in COVID-19 patients: A Meta-Analysis

“…Thus, 28 articles included 991 COVID-19 patients underwent tocilizumab administration were included in this study 10,11, . Of the 28 included studies, 7 of which included 377 patients were case-control studies with a control group not using tocilizumab 28,29,32,36,39,40,42 .…”

“…At the point of study completion, median LOH and LOI was 14 days (range 11-34) and 8 days (range [5][6][7][8][9][10][11] in patients receiving tocilizumab, which was speci ed in 15 studies 10,[20][21][22][23]28,29,31,32,35,36,[38][39][40][41] and 8 studies 10,23,27,29,32,33,36,42 , separately. Moreover, the median duration of mechanical ventilation was 7 days (range 5-10) after treatment of tocilizumab which was documented in 9 articles 10,11,[21][22][23]27,28,40,41 ( Table 2).…”