Tocilizumab associated with better outcomes from COVID-19 in US study
Simon Collins, HIV i-Base
Another large observational cohort has reported positive results from using the anti-IL-6 monoclonal antibody tocilizumab to treat COVID 19. 
The rationale for benefit is related to high levels of IL-6 associated with the cytokine storm in late and more serious COVID-19. This study adds to growing evidence suggesting benefit including those previously reported in this bulletin. [2, 3]
The current study, published on 14 August 2020 in Lancet Rheumatology, was a retrospective cohort analysis from 13 hospitals in New Jersey, US.
Between 1 March and 22 April 2020 a total of 764 adults with COVID-19 hospitalised in the intensive care units and 210 (27%) of these used tocilizumab.
Significant baseline differences in people using tocilizumab included being younger: median age 62 years (IQR: 53 to 71) vs 68 years (IQR: 58 to 78); p=0.0003; more likely to be male (74% vs 63%, p=0.0037); and less likely to be in nursing home (5% vs 14%, p=0.0004). There were no significant differences in terms of comorbidities but a higher likelihood of using hydroxychloroquine or azithromycin.
A propensity score-matched population included 630 adults, 210 who received at least one infusion of tocilizumab and 420 who did not receive tocilizumab. Nearly everyone (206/210, 98%) received 400 mg flat dosing, two received 8 mg/kg, and two received other doses; 185 (88%) received one infusion and 25 (12%) received a second infusion.
Mortality was 57% (358/639) overall but in adjusted analysis was significantly lower in the tocilizumab group 102 (49%) vs 256 (61%): HR 0.64 (95% CI: 0.47 to 0.87); p=0·0040.
Median survival from time of admission was not reached for tocilizumab (95% CI 23 days to not reached) vs 19 days (16 to 26), with a hazard ratio 0.71 (95% CI: 0·56 to 0·89) p=0·0027.
These associations were similar in subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher.
These results add to the growing number of studies that have reported potentially positive results with tocilizumab. Four earlier studies were reviewed in a recent earlier issue of HIV and COVID-19. 
Many other prospective studies are already ongoing, including the large UK RECOVERY study, using a randomised design. 
Based on limited success with all approaches based on monotherapy, combination approaches should be prioritised, with at least one study looking at tocilizumab plus remdesivir. 
Although the risk of serious infections related to tocilizumab is not considered greater than placebo, two cases were reported as we went to press of acute HSV-1-mediated liver failure, both fatal, in two Italian COVID-19 patients treated with tocilizumab. 
However, the large randomised placebo-controled COVACTA study failed to show any benefit from tocilizumab. 
- Biran N et al. Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. The Lancet Rheumatology. DOI: 10.1016/S2665-9913(20)30277-0. (14 August 2020).
- Collins S. Further positive reports from tocilizumab to treat COVID-19. HTB (22 July 2020).
- Collins S. Potential for tocilizumab to treat moderate to severe COVID-19. HTB (14 May 2020).
- RECOVERY study
- Tocilizumab and remdesivir in new dual therapy study. (1 June 2020).
- Busani S et al. Two fatal cases of acute liver failure due to HSV-1 infection in COVID-19 patients following immunomodulatory therapies. CID ciaa1246. DOI: 10.1093/cid/ciaa1246. (25 August 2020).
- Collins S. Tocilizumab fails to meet clinical endpoints in randomised COVACTA study: other studies continue. HTB (9 September 2020).
This article was originally posted on 21 August 2020 and updated on 9 September 2020..