Tocilizumab fails to convince in three new COVID-19 trials

Three newly released studies suggest a potential role for tocilizumab in COVID-19 but do not provide enough evidence of efficacy to support routine use of the drug, experts say.

Published in JAMA Internal Medicine, the three trials – two of them RCTs – fail to confirm the positive results seen with the IL-6 inhibitor in earlier observational studies.

One Italian RCT involving 126 patients hospitalised with COVID-19 found no effect of tocilizumab on disease progression and the trial was terminated early due to lack of benefit. A French trial conducted in 131 hospitalised patients requiring oxygen found that tocilizumab might have reduced the need for invasive or non-invasive ventilatory support but it had no effect on mortality at 14 or 28 days.

And a large US retrospective study involving more than 3900 critically ill patients found that the risk of in-hospital mortality was lower in patients treated with tocilizumab in the first two days of ICU admission compared with patients whose treatment did not include early use of tocilizumab (Hazard Ratio 0.71). However the trial was not randomised so the findings could be subject to confounding, the researchers said

An accompanying editorial said the disappointing results from three new studies were a sobering reminder that promising findings from numerous observational studies did not translate into benefit for tocilizumab in severe COVID-19 pneumonia when tested in robust prospective trials.

“Their findings do not support the routine use of tocilizumab for COVID-19 in most settings. 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,” wrote Dr Jonathan Parr, of the Division of Infectious Diseases, University of North Carolina.

A similar note of caution was struck by Professor David Henry, a rheumatologist and clinical pharmacologist at Bond University, Queensland, who said a decision on use of tocilizumab in COVID-19 should await the outcomes of larger RCTs.

He noted that the COVACTA study conducted by Roche appears not to have met its primary endpoint of improved clinical status in COVID-19 pneumonia, and a trial of another IL-6 blocker, sarilumab, in COVID-19 stopped recruiting patients with less advanced disease because of futility in this group.

“The largest ongoing trial of tocilizumab (over 850 patients) is the Recovery Trial being coordinated by Oxford University, and the results have not yet been reported,” said Professor Henry.

“So, while the results of non-randomised studies have suggested possible benefits of tocilizumab, the two small randomised trials reported today are inconclusive about mortality. As with other drugs in COVID-19 we must wait for the results of large definitive randomised trials.”

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