Tocilizumab for COVID-19? Three Studies Yield Mixed Findings

By Amy Orciari Herman

Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM

Three new studies in JAMA Internal Medicine add to the evidence on tocilizumab for COVID-19 but reach no definitive conclusion on whether the drug works — or not. Tocilizumab is a humanized monoclonal antibody that acts against the interleukin-6 receptor.

First, U.S. researchers retrospectively compared roughly 430 critically ill COVID-19 patients who received intravenous tocilizumab within 2 days of ICU admission with 3500 ICU patients who didn't receive tocilizumab within that time frame. Some 29% of the tocilizumab group versus 41% of the comparator group died in the hospital. After multivariable adjustment, early tocilizumab use was associated with nearly a 30% reduction in mortality risk. The researchers caution, however, about residual confounding.

Next, in a randomized, open-label trial in Italy, some 125 patients hospitalized with COVID-19 pneumonia were assigned to tocilizumab or standard care. The primary endpoint — clinical worsening within 14 days — did not differ significantly between the groups (27%–28%).

And in another randomized, open-label trial, roughly 130 COVID-19 patients in France with moderate-to-severe pneumonia were assigned to tocilizumab or usual care. One primary outcome, clinical progression at day 4, was not improved with tocilizumab. The other primary outcome — death or need for high-flow oxygen or ventilation at day 14 — favored tocilizumab (24% vs. 36% of usual-care patients). However, by day 28, there was no mortality difference.

An editorialist notes that randomized trial findings to date "do not support the routine use of tocilizumab for COVID-19 in most settings." He adds, "I plan to wait out the torrent of positive observational studies and reconsider tocilizumab's use in COVID-19 if, and only if, more compelling data from randomized trials emerges."