Final results of the open-label, randomised, controlled CORIMUNO-TOCI-1 trial published in the JAMA Internal Medicine journal on 20 October 2020
In some patients with COVID-19 pneumonia, a hyper-inflammatory state of immunological origin contributes to acute respiratory failure and death. The CORIMUNO-19 platform was rapidly set up to evaluate the efficacy and tolerance of various immune modulators in adult patients with moderate to severe COVID-19 infection, with a series of multicentre, controlled, randomised trials that started on 27 March 2020.
Tocilizumab is a monoclonal antibody that blocks the interleukin-6 cytokine receptor. The final results of the multicentre, open-label, controlled, randomised tocilizumab trial were published following peer review on 20 October 2020 in the JAMA Internal Medicine journal (https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772187).
The final results of this trial confirm the preliminary results communicated on 27 April 2020. They should be independently corroborated by additional trials.
The patients included were hospitalised for moderate to severe COVID-19 pneumonia, requiring at least 3 L/mn of oxygen but not requiring intensive care upon admission.
The primary composite endpoint on which the analysis was based to evaluate the effectiveness of the treatment was the combination of the need for ventilation (mechanical or non-invasive) or death at D+14.[1]
In total, 130 patients with a median age of 64 years were included in this open-label, randomised clinical trial: 67 to standard of care alone and 63 to standard of care associated with tocilizumab.
On inclusion, the median needs in oxygen were 5L/mn. The proportion of patients who required non-invasive ventilation, intubation or had died on the 14th day was 36% with the standard of care and 24% with the tocilizumab.
No difference in mortality at 28 days was observed between the two arms (11.1% and 11.9% respectively).
Thus, on day 14, the risk of dying or resorting to non-invasive or mechanical ventilation was reduced by 33% in the group treated with tocilizumab.
The proportion of patients requiring transferral to intensive care was reduced by a half in the tocilizumab arm (18%) compared to the standard treatment arm (36%). The percentage of patients who had been discharged from hospital by day 28 was higher in the tocilizumab group than in the standard treatment group: 83% versus 73%.
Finally, tocilizumab did not result in more adverse effects than the standard treatment.
Several CORIMUNO trials testing other immunomodulators are currently being analysed and the combination of tocilizumab with dexamethasone is being tested in another CORIMUNO protocol.
This multicentre trial was conducted through the Assistance Publique - Hôpitaux de Paris/Université Paris-Saclay/Université de Paris/INSERM-REACTing COVID-19 academic research collaboration
· Coordinating investigator: Pr O. Hermine, Hôpital Necker, AP-HP, Imagine Institute, INSERM U1163, Université de Paris
· Co-coordinating investigator: Pr X. Mariette, Hôpital Bicêtre, AP-HP, INSERM U1184, Université Paris-Saclay
· Scientific Director: Dr P.L. Tharaux, Paris Centre de Recherche Cardiovasculaire (PARCC), INSERM U970, Hôpital Européen Georges Pompidou, AP-HP, Université de Paris.
· Design and coordination of the CORIMUNO trial platform: Pr P. Ravaud, Center for Clinical Epidemiology, Hôpital Hôtel Dieu, AP-HP, CRESS, INSERM U1153, Université de Paris
· Statistician: Pr P. Ravaud, Center for Clinical Epidemiology, Hôpital Hôtel Dieu, AP-HP, CRESS, INSERM U1153, Université de Paris
· Monitoring and data management: Pr M. Resche-Rigon (Clinical Trial Unit, Hôpital Saint Louis, AP-HP), CRESS, INSERM U1153, Université de Paris.
· Organisation of the data collection: Pr M Dougados, Hôpital Cochin, AP-HP, CRESS, INSERM U1153, Université de Paris
The CORIMUNO-19 trials platform is sponsored and funded by Assistance Publique-Hôpitaux de Paris, and supported by INSERM via the REACTing consortium.
The trial received grant support from the Programme Hospitalier de Recherche Clinique of the French Ministry of Health, seed funding from the INSERM via the REACTing consortium via the Fondation pour la Recherche Médicale, Paris, France, and a grant from the Fondation AP-HP pour la recherche, Paris, France. The tocilizumab and 4000 Elecsys interleukin-6 dosage kits were supplied without conditions by the Roche laboratory, which was involved in neither trial design, data collection, analysis, interpretation, manuscript writing nor in the governance of the trial.
[1] Non-invasive ventilation covers all of the ventilatory support techniques, except for endo-tracheal devices, i.e. with no intubation nor tracheotomy.
