COVID-19: Support for further investigation of tocilizumab
medwireNews: Add-on treatment with the interleukin (IL)-6 inhibitor tocilizumab may improve outcomes for patients with severe COVID-19, suggest findings from two retrospective cohort studies.
In the first, published in The Lancet Rheumatology, Cristina Mussini (University of Modena and Reggio Emilia, Italy) and team evaluated the outcomes of 544 hospitalized patients with severe COVID-19 pneumonia who were treated with regional standard of care involving supplemental oxygen, hydroxychloroquine, combination antiretrovirals, azithromycin, and/or low molecular weight heparin between 21 February and 30 April 2020.
Of these, 179 patients also received tocilizumab – either two doses of 8 mg/kg given intravenously or two doses of 162 mg given subcutaneously – based on local availability. A total of 30% of patients in the tocilizumab group subsequently commenced glucocorticoids, as did 17% of those in the standard care group.
Rates of invasive mechanical ventilation were similar in the tocilizumab and control groups, at 18% and 16%, respectively, but a significantly lower proportion of patients in the tocilizumab group died, at 7% versus 20%.
Tocilizumab was associated with a significant reduction in the risk for the combined endpoint of mechanical ventilation or death, with a hazard ratio of 0.61 after adjustment for a range of factors including age, sex, and symptom duration. Mussini and team note that these findings remained consistent after further adjustment for baseline C-reactive protein levels, comorbidities, or glucocorticoid use.
In the safety analysis, patients treated with tocilizumab had a significantly higher risk for new infections (13 vs 4%) than those in the control group, and one patient treated with tocilizumab and high-dose glucocorticoids died after experiencing severe liver failure due to herpes simplex virus 1 reactivation.
“The study design and short follow-up period do not allow us to make conclusions regarding the early and long-term side-effects of receiving tocilizumab followed by glucocorticoids; data from ongoing randomised clinical trials are required,” write the researchers.
In an accompanying comment, Grant Schulert (University of Cincinnati, Ohio, USA) says that Mussini and team’s study “is the largest of its kind reported thus far” and “provides strong evidence that tocilizumab might prevent intubation and death in adults with severe COVID-19 pneumonia.”
Nonetheless, he points out that “[t]he precise group of patients who might benefit from tocilizumab and the optimal biomarkers for identifying cytokine storm in the setting of COVID-19 remain[s] unknown.”
And Schulert believes “[t]he most crucial question concerns the relative utility of tocilizumab treatment versus other non-specific immunomodulatory agents (including corticosteroids) and other cytokine-directed therapies, which is the focus of multiple ongoing randomised trials.”
The results of the Italian study are supported by a smaller study from Cleveland Clinic in Ohio, USA, which also compared the outcomes of hospitalized patients with severe COVID-19 who received standard treatment with (n=28) or without (n=23) concomitant tocilizumab between 13 March and 19 April 2020.
Local standard treatment involved systemic corticosteroids, hydroxychloroquine, or azithromycin for most patients, and tocilizumab was given when patients had hypoxia, lung infiltrates on chest radiography, elevated inflammatory markers, risk for clinical deterioration, and no contraindications.
Bassel Akbik and co-authors report in EClinicalMedicine that among the 25 patients who required vasopressor support, those receiving tocilizumab (n=16) had a significantly shorter median duration of vasopressor support than those in the control group, at 2 versus 5 days.
The median time to clinical improvement in patients who required mechanical ventilation was numerically, but not significantly, lower in the tocilizumab compared with the control group (8 vs 13 days), as was the median duration of mechanical ventilation (7 vs 10 days).
“[O]ur findings suggest that use of tocilizumab in selected patients with severe COVID-19 may provide clinical benefit,” say the researchers, but they stress the need for validation in randomized controlled trials.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group
29 June 2020: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.