Current best evidence for clinical care (more info)
BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear.
METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses.
RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo.
CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).
| Discipline / Specialty Area | Score |
|---|---|
| Intensivist/Critical Care | |
| Respirology/Pulmonology | |
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Infectious Disease | |
Unfortunately, this carefully done randomized placebo-controlled trial found no benefits from tocilizumab treatment in hospitalized COVID-19 patients.
As a surgeon, information like this is rarely considered. This excellent article shows how difficult it is to treat patients who exhibit a complicated response to Covid-19.
This trial (along with others published this week) provides evidence to guide practice for tociliziumab in COVID-19. While there is still some uncertainty, it is now clear that the effects of this medication are small and should not be widely used outside of clinical trials. Enthusiasm for off-label use of this medication should be tempered.
This study is well done methodologically. Despite a negative signal, there has been enough interest in tociluzimab that I think stakeholders are interested.
Useful to keep up with this info.
Timely and important negative study. It opens up opportunity, resources, and volunteers for other potentially efficacious agents in treating COVID-19 infection.
Randomized, blinded trial in multiple hospitals in Boston in patients with moderate disease from Covid-19. Tocilizumab did not alter need for intubation or mortality. Strong evidence against use of this agent for moderate Covid-19 disease.