Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls

Abstract

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case–control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion–exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04965-6.

Macrophage Activation Syndrome in Viral Sepsis

“…Regarding IL-6 blockade with tocilizumab in COVID-19-associated MAS, the results are controversial. Some studies have reported that treatment with tocilizumab contributes to reduced mortality and favorable outcomes [144,145]. Conversely, another study noted that tocilizumab demonstrated limited efficacy for COVID-19-related MAS [146].…”

Advances in attractive therapeutic approach for macrophage activation syndrome in COVID-19

“…Overzealous immune responses associated with MAS, may be driving COVID-19 related ARDS ( 21 ). There has been research shows that treatment of MAS, such as the use of tocilizumab and the combination of tocilizumab and steroids, significantly reduced the intubation or death of severe patients ( 31 , 32 ).…”

Tocilizumab treatment in COVID-19: A prognostic study using propensity score matching

“…9 In cases of severe COVID-19 pneumonia, patients who received TCZ were shown to have better outcomes, and retrospective observational cohort studies revealed an immediate decrease in fever, decreased need for oxygen therapy and mechanical ventilation, as well as an improvement in lung symptoms. [10][11][12][13][14]…”