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?:abstract
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BACKGROUND: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19 We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters METHODS: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion;and if needed a second infusion 24 to 72 h later) A control group was retrospectively selected with the same inclusion criteria Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology RESULTS: Among the 96 patients included (81% male, mean (SD) age: 60 (12 5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs 89%, wHR: 0 39 [0 25-0 56];p < 0 001) Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs 45%;wHR: 0 58 [0 36-0 94];p = 0 026) However, tocilizumab did not improve overall survival (wHR = 0 68 [0 31-1 748], p = 0 338) Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs 73 5%, wHR = 1 66 [1 17-2 37], p = 0 005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs 16 days;p < 0 001) At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs 40%, wHR = 1 82 [1 22-2 75];p = 0 003) The levels of CRP and fibrinogen post therapy (p < 0 001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model) Rates of neutropenia (35% vs 0%;p < 0 001) were higher in the tocilizumab group, yet rates of infections (22% vs 38%, p = 0 089) including ventilator-acquired pneumonia (8% vs 26%, p = 0 022) were higher in the control group CONCLUSION: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit
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