Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial

Abstract

Purpose Trials of tocilizumab in patients with severe COVID-19 pneumonia have demonstrated mixed results, and the role of tocilizumab in combination with other treatments is uncertain. Here we evaluated whether tocilizumab plus remdesivir provides greater benefit than remdesivir alone in patients with severe COVID-19 pneumonia. Methods This randomized, double-blind, placebo-controlled, multicenter trial included patients hospitalized with severe COVID-19 pneumonia requiring > 6 L/min supplemental oxygen. Patients were randomly assigned (2:1 ratio) to receive tocilizumab 8 mg/kg or placebo intravenously plus ≤ 10 days of remdesivir. The primary outcome was time from randomization to hospital discharge or “ready for discharge” (defined as category 1, assessed by the investigator on a 7-category ordinal scale of clinical status) to day 28. Patients were followed for 60 days. Results Among 649 enrolled patients, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. 566 patients (88.2%) received corticosteroids during the trial to day 28. Median time from randomization to hospital discharge or “ready for discharge” was 14 (95% CI 12–15) days with tocilizumab plus remdesivir and 14 (95% CI 11–16) days with placebo plus remdesivir [log-rank P = 0.74; Cox proportional hazards ratio 0.97 (95% CI 0.78–1.19)]. Serious adverse events occurred in 128 (29.8%) tocilizumab plus remdesivir and 72 (33.8%) placebo plus remdesivir patients; 78 (18.2%) and 42 (19.7%) patients, respectively, died by day 28. Conclusions Tocilizumab plus remdesivir did not shorten time to hospital discharge or “ready for discharge” to day 28 compared with placebo plus remdesivir in patients with severe COVID-19 pneumonia. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06507-x.

Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids

“…There were a total of 2117 patients receiving simple oxygen only, 2505 receiving NIV, and 717 receiving IMV in 15 studies from multiple countries and continents. 1,[25][26][27][28][29][30][31][32] Table 1 shows the number of deaths and total patients in each RCT reported in the WHO Working Group publication and included in this reanalysis. As expected, smaller studies showed wider confidence intervals, and these studies were more likely to be unpublished studies.…”

COVID-19, Influenza and RSV: Surveillance-informed prevention and treatment – Meeting report from an isirv-WHO virtual conference

“…No benefit was observed in those not on corticosteroids. The REMDACTA trial evaluated whether tocilizumab plus remdesivir in hospitalized patients provided greater benefit than remdesivir alone, but the combination did not shorten time to hospital discharge or reduce mortality ( Rosas et al, 2021 ), although a WHO meta-analysis concluded that use of IL-6 antagonists reduced mortality ( Shankar-Hari et al, 2021 ). Several hundred studies are underway with over 50 anti-inflammatory agents.…”

Roles of host mitochondria in the development of COVID-19 pathology: Could mitochondria be a potential therapeutic target?

“…On the other hand, tocilizumab and sarilumab are monoclonal antibodies against IL-6 and believed to have a potential role against COVID-19 by inhibiting IL-6 mediated inflammation. However, a recent clinical trial found that these antibodies have not shown any better clinical outcomes or lower mortality rates alone or combined with remdesivir [198][199][200][201].…”