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. [1]

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.

comments

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. [3]

Many other prospective studies are already ongoing, including the large UK RECOVERY study, using a randomised design. [4]

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. [5]

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. [6]

However, the large randomised placebo-controled COVACTA study failed to show any benefit from tocilizumab. [7]

References

1. 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).
   https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30277-0/fulltext
2. Collins S. Further positive reports from tocilizumab to treat COVID-19. HTB (22 July 2020).
   https://i-base.info/htb/38523
3. Collins S. Potential for tocilizumab to treat moderate to severe COVID-19. HTB (14 May 2020).
   https://i-base.info/htb/37877
4. RECOVERY study
   http://www.recoverytrial.net
5. Tocilizumab and remdesivir in new dual therapy study. (1 June 2020).
   https://i-base.info/htb/38076 
6. 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).
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1246/5896943
7. Collins S. Tocilizumab fails to meet clinical endpoints in randomised COVACTA study: other studies continue. HTB (9 September 2020).
   https://i-base.info/htb/38965

This article was originally posted on 21 August 2020 and updated on 9 September 2020..