No benefit of tocilizumab for people with severe COVID-19
medwireNews: Adding tocilizumab to standard care does not improve clinical outcomes for people with severe or critical COVID-19 and may increase mortality risk, according to findings from the TOCIBRAS trial published in The BMJ.
“These results raise questions about an anti-inflammatory approach in the treatment of covid-19 beyond corticosteroids,” say Viviane Veiga (BP-A Beneficência Portuguesa de São Paulo, Brazil) and co-investigators.
In all, 28% of 65 patients randomly assigned to receive a single infusion of tocilizumab 8 mg/kg alongside local standard care experienced the composite outcome of mechanical ventilation or death during 15 days of follow-up, compared with 20% of 64 patients given standard care only, a nonsignificant difference (odds ratio [OR]=1.54).
However, mortality rates at the 15-day follow-up were significantly higher among patients in the tocilizumab group compared with those in the control group, with rates of 17% versus 3% and an OR of 6.42.
Although mortality risk at this timepoint “was not a prespecified outcome in the trial, but rather a component of the primary outcome, a detrimental effect on this end point raised concerns about safety, and the data monitoring committee therefore recommended early termination of the trial,” explain the researchers.
In the safety analysis, adverse events (AEs) occurred in 43% of patients given tocilizumab and 34% of those given standard care, while serious AEs were reported in 16% and 11%, respectively. The most frequently reported severe AE in the tocilizumab group was elevated alanine aminotransferase, aspartate aminotransferase, or bilirubin levels, affecting 10% of patients compared with 5% of those in the placebo group.
The TOCIBRAS investigators caution that their study had a number of limitations, including its open-label design and small patient numbers.
“[T]he 95% confidence interval around the effect on the primary outcome was wide, compatible with odds ratios between 0.66 (benefit of tocilizumab) and 3.66 (harm with tocilizumab),” they add.
In a comment to the press, Peter Horby, Professor of Emerging Infectious Diseases at the University of Oxford in the UK, said that “much larger trials are needed to resolve the continuing uncertainty about the role of tocilizumab in the treatment of patients with COVID.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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