#VisualAbstract: Tocilizumab not superior to standard care in randomized controlled trial for severe COVID-19 patients

1. Tocilizumab was not superior to standard care after 15 days, for COVID-19 patients in serious condition.

2. Patients given tocilizumab had higher rates of mortality and adverse events, but shorter hospital stays compared to the standard care group.

Evidence Rating Level: 1 (Excellent)

Study rundown: The COVID-19 pandemic has resulted in nearly 100 million diagnoses worldwide. Although the disease presents with mild to no symptoms in most individuals, a significant number develop pneumonia that progresses to complications. These include complications such as respiratory failure, shock, organ failure that can lead to death, contributing to over 2 million deaths worldwide. One of the current hypotheses surrounding the downstream complications of COVID-19 are that they result from a host immune response involving inflammatory cytokines and chemokines. For instance, IL-6 is an inflammatory cytokine that has been found to have a role in controlling infections, such as SARS-CoV-1 and influenza A. Therefore, tocilizumab has been proposed as a possible therapy in severe COVID-19 cases since it is an Il-6 inhibitor, and so could potentially downsize the immune response. The current study compared tocilizumab versus standard care, in a randomized controlled trial among patients hospitalized with severe COVID-19. The trial was carried out at 9 hospitals in Brazil, with 64 patients in the standard care group, and 65 in the tocilizumab group (who each received a single intravenous infusion with a dose of 8 mg/kg). Each participants’ clinical status was assessed after 15 days. Ultimately, tocilizumab was found to be non-superior to standard care for severe COVID-19 cases, and in fact, had a higher percentage of patients on mechanical ventilation or passing away after the 15 day mark (28% versus 20%). In introducing the therapeutic agent, there was also a higher rate of adverse events in the tocilizumab group (43% versus 34%), though these patients also interestingly had a shorter average hospital stay (mean 11.3 versus 14.7 days). Overall, study findings did not yield evidence supporting the usage of tocilizumab for severe COVID-19 cases, though further investigation may be warranted for its suitability for usage earlier in the disease course.

Click to read this article in the BMJ

Relevant Reading: Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia

In-Depth [randomized controlled trial]: The study population consisted of 129 adult patients (68% male) enrolled between May and July 2020. This was ended prematurely due to the increased mortality in the tocilizumab group. In order to be classified as a severe COVID-19 case, patients must have had a confirmed diagnosis, been symptomatic for three days, confirmed pulmonary infiltrates on imaging, and were receiving supplemental oxygen or mechanical ventilation. The results of the study found that tocilizumab was not superior to standard care, since after 15 days, 28% in the tocilizumab group and 20% in the standard care group were on a mechanical ventilator or had passed away (odds ratio 1.54, 95% CI 0.66-3.66, p = 0.32). For mortality specifically, 17% in the tocilizumab group and 3% in the standard care group had passed away after 15 days (OR 6.42, 95% CI 1.59-43.2), and there was also no significant difference in mortality after 28 days (OR 2.70, 95% CI 0.97-8.35). However, patients in the tocilizumab group had a shorter average hospital stay (mean 11.3, SD 8.0 for tocilizumab; mean 14.7, SD 8.2 for standard care; rate ratio 0.70, 95% CI 0.55-0.87). Other outcomes such as secondary infection, thromboembolism, ventilator-free days, and independence from supplemental oxygen yielded no significant difference.

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