Tocilizumab associated with improved outcomes in patients with COVID-19
medwireNews: Treatment with the interleukin (IL)-6 receptor inhibitor tocilizumab may be associated with a reduction in time on mechanical ventilation, shorter hospital stay, and decreased mortality risk among patients with severe COVID-19, suggest findings from three studies conducted in Sweden and the USA.
Swedish study: Shorter hospital stay and duration of ventilation
In the first study, Johannes Eimer and team from Karolinska University Hospital Huddinge in Stockholm retrospectively evaluated the outcomes of 87 patients with confirmed SARS-CoV-2 infection who were admitted to the intensive care unit (ICU) at the hospital between 11 March and 15 April 2020. A total of 33% were treated with a single dose of tocilizumab 8 mg/kg according to physician discretion prior to or at the time of ICU admission, while the remaining 67% received usual care only.
The researchers report in a letter to the Journal of Internal Medicine that rates of the primary outcome of 30-day all-cause mortality were numerically lower among patients treated with tocilizumab than in control patients (17.2 vs 32.8%), but the between-group difference did not reach statistical significance.
However, patients in the tocilizumab group had significantly more ventilator-free days than those in the control group (median 19.0 vs 9.0 days), as well as a significantly shorter stay in the ICU (median 12.0 vs 20.0 days) and in hospital overall (20.5 vs 30.0 days).
Eimer and colleagues note that these findings “were confirmed in a propensity score-matched sub-cohort,” and that tocilizumab “was well tolerated and not associated with an increased rate of serious adverse events during the study period.”
US study: Improved mortality rates in some patients
The second study, also published as a letter to the Journal of Internal Medicine, was a retrospective investigation including 42 COVID-19 patients hospitalized at the Swedish Medical Center in Seattle, Washington, between 16 March and 17 April 2020 who were treated with tocilizumab, and 41 matched controls who did not receive the IL-6 inhibitor.
Overall rates of 7-day mortality and hospital discharge were comparable among patients who did and did not receive tocilizumab, at 21.4% versus 26.8% and 16.7% versus 17.1%, respectively. However, Krish Patel and colleagues from the institution say that among patients with severe COVID-19, mortality rates at day 7 were notably lower in the tocilizumab compared with the control group (14.2 vs 28.6%), while hospital discharge rates were “slightly higher” (33.3 vs 28.6%).
These findings suggest that tocilizumab “may improve outcomes for select patients with COVID-19 and warrants further study,” they write.
US study: Reduced mortality risk in the ICU
In the third study, Andrew Ip (Hackensack University Medical Center, New Jersey) and colleagues retrospectively evaluated the outcomes of 630 patients with confirmed SARS-CoV-2 infection who required ICU support at one of 13 hospitals in New Jersey.
During a median follow-up of 22 days, 49% of 210 patients treated with tocilizumab according to physician discretion died during or after hospitalization, compared with 61% of 420 propensity score-matched patients who did not receive tocilizumab. Median overall survival from the time of admission was not reached in the tocilizumab group compared with 19 days in the control group, translating into a significant 36% lower mortality risk with tocilizumab on multivariable analysis.
In a post-hoc analysis of 558 patients with available C-reactive protein (CRP) data, Ip and team found that tocilizumab was associated with a significant reduction in mortality risk among the 286 patients with CRP levels of 15 mg/dL or higher, but not among those with lower levels, “potentially suggesting that tocilizumab could exert its effects among patients whose COVID-19 illness is progressing to an inflammatory state.”
In a commentary accompanying the research published in The Lancet Rheumatology, Corrado Campochiaro and Lorenzo Dagna, both from Vita-Salute San Raffaele University in Milan, Italy, say that these findings “offer important real-life insight into the use of tocilizumab in the most critically ill population of mechanically ventilated patients admitted to the intensive care unit.”
While they acknowledge “the inherent limitations of a retrospective study,” the commentators stress that “[o]bservational studies are important in a rapidly evolving pandemic because they can offer clues for reshaping the design of future or ongoing randomised trials.”
And the study authors conclude: “Current evidence supports continued evaluation of tocilizumab in a randomised trial for patients with severe COVID-19.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group
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