At last – some positive results for tocilizumab in COVID-19

After mixed results in previous randomised trials, the IL-6 inhibitor tocilizumab has shown positive effects in treating critically ill patients with COVID-19 in a study from Europe.

The preliminary findings, which are yet to be published, come from 303 patients with severe COVID-19 pneumonia enrolled in the REMAP-CAP trial, led by Imperial College London and the Intensive Care National Audit & Research Centre (ICNARC) in the UK and Utrecht University in the Netherlands.

The trial is evaluating the effect of several immune modulation treatments: tocilizumab, sarilumab, anakinra and interferon on a combination of survival and length of time patients need support in an ICU.

Results from the first 303 patients show that treatment with tocilizumab yielded an estimated odds ratio of 1.87 for a better outcome compared to no immune modulation, with a high degree of statistical certainty (99.75% probability that tocilizumab is superior to no immune modulation).

The outcome of improvement measured was a combination of organ support in the ICU and surviving the hospital admission.

But the investigators cautioned that they did not yet have data on the relative contribution of survival and reduced length of time needing organ support in ICU, or the relative benefits of tocilizumab compared to the other immune modulators.

Study investigator Professor Anthony Gordon, a Consultant in Intensive Care Medicine at Imperial College Healthcare NHS Trust, London, said the OR of 1.87 for tocilizumab compared favourably to an OR of 1.43 previously seen with dexamethasone.

“These early findings show that treatment with this immune modulating drug is effective for critically ill COVID-19 patients in intensive care units. When we have the results available from all participants, we hope our findings will offer clear guidance to clinicians for improving the outcomes of the sickest COVID-19 patients,” he said

Professor Peter Horby, an Infectious Diseases specialist at Oxford University, said positive results with dexamethasone in severe COVID have provided proof of principle that anti-inflammatory drugs can help, and the findings for tocilizumab are an encouraging result which suggests that other, more targeted, anti-inflammatory drugs may also be of benefit.

“The results so far on tocilizumab have been mixed, with four randomised controlled trials having reported results, of which two were negative and two were positive. None have reported a mortality benefit at day 28 or 30. The results from REMAP-CAP add to this evidence base and I eagerly look forward to seeing the full results,” he said.

Prof Athimalaipet Ramanan, Honorary Professor of Paediatric Rheumatology, University of Bristol, said tocilizumab may be of benefit to certain patients with COVID-19, but it is difficult to identifying these patients based on early data that is not yet published.

“RECOVERY trial’s data on Tocilizumab is yet to be published. The key difference between the 2 studies (RECOVERY and REMAP-CAP) is that REMAP-CAP recruits more severely ill patient (about to be ventilated or ventilated),” he noted.

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