Further positive reports from tocilizumab to treat COVID-19

22 July 2020. Related: COVID-19: investigational drugs, COVID-19.

Simon Collins, HIV i-Base

Two new publications provide additional reports of positive outcomes from using the anti-IL-6 monoclonal antibody tocilizumab to treat COVID-19.

The largest of these is a retrospective analysis of 544 patients hospitalised with severe COVID-19. Results were reported by Giovanni Guaraldi from University of Modena on 24 June in Lancet Rheumatology. [1]

Median age was 67 years (IQR: 56 to 77) and 359 (66%) men, with more severe baseline characteristics in participants who received tocilizumab.

Overall, 179/544 participants received open-label tocilizumab and 365/544 received standard of care. Of these, a similar percentage progressed to need mechanical ventilation: 57 (16%) vs 33 (18%), p=0.41, for the SoC and tocilizumab groups respectively. These results were similar for both intravenous (n=88) and subcutaneous (n=91) formulations of tocilizumab.

However, mortality was significantly higher in people just receiving SoC: 73 (20%) vs 13 (7%) in SoC vs tocilizumab, p<0·0001).

In multivariate analysis, adjusting for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab was associated with a significantly reduced risk of invasive mechanical ventilation or death (adj. HR 0·61, 95% CI: 0.40 to 0.92; p=0·020).

Tocilizumab was also associated with significantly fewer new infections: 24/179 (13%) vs 14/365 (4%), p<0·0001).

The second report was from an observational US cohort of 27 people hospitalised with SARS-CoV-2 pneumonia who received tocilizumab. Median age was 63 years (IQR: 51 to 75 years) and 23/27 were men. Seventeen patients (63%) had a significant comorbidity, including hypertension in 12/17. [2]

Participants received a 400 mg intravenous dose of tocilizumab as part of a compassionate access programme at a single site in Los Angeles. Participants also received hydroxychloroquine and azithromycin, with 7/27 on blinded placebo-controlled remdesivir study.

At baseline, all participants were already receiving oxygen support with oxygen levels <90%, with most (21/27) on mechanical intubation. All showed IL-6 as the predominant cytokine.

Although tocilizumab was associated with significant rapid reductions in temperature and CRP, 4/27 showed no response, and 3/4 progressed with poorer outcomes. The paper discussed whether the non-responses might have been different with higher dosing.

Two deaths, at days 3 and 11, were not judged to be linked to tocilizumab.

The report concluded that these results were significantly better than historical reports with hypothetical mechanism for reducing elevated IL-6 that is associated with severe COVID-19 and poor prognosis.

comments

Although small retrospective analyses, 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 already using tocilizumab plus remdesivir. [5]

References

1. Guaraldi G et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. The Lancet Rheumatology, DOI: 10.1016/S2665-9913(20)30173-9. (24 June 2020).
   https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30173-9
2. Jordan SC et al. Compassionate use of tocilizumab for treatment of SARS-CoV-2 pneumonia. Clinical Infectious Diseases, ciaa812, DOI: 10.1093/cid/ciaa812. (23 June 2020).
   https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa812/5861638
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