medwireNews: Treatment with the interleukin (IL)-6 receptor inhibitor sarilumab does not improve clinical outcomes for people with severe or critical COVID-19, trial results suggest.
The phase 3 study – conducted at 45 centers in Asia, Europe, the Middle East, and North and South America – involved 416 hospitalized patients with SARS-CoV-2 infection and pneumonia who required supplemental oxygen, mechanical ventilation, or intensive care unit admission. Participants were randomly assigned in a 2:2:1 ratio to receive a single dose of intravenous sarilumab 400 mg, 200 mg, or placebo (with an optional second dose after 24–48 hours) in addition to local standard care.
François-Xavier Lescure (Bichat-Claude Bernard Hospital, Paris, France) and co-investigators from the Sarilumab COVID-19 Global Study Group found that the median time to clinical improvement (by ≥2 points on a 7-point scale) during 29 days of follow-up was comparable among patients given sarilumab 400 mg, sarilumab 200 mg, and placebo, at 10, 10, and 12 days, respectively. Survival rates were also similar in the sarilumab 400 mg and 200 mg versus placebo groups (92 and 90 vs 92%, respectively).
The researchers propose “several potential reasons” why sarilumab did not demonstrate efficacy in their trial, including that patients were not selected for inclusion based on markers of inflammation or worsening prognosis.
“[W]e might not have included a sufficient number of patients for whom immunomodulatory therapy would have been appropriate [or] chosen an optimal time in the disease course of COVID-19 to administer sarilumab,” they write in The Lancet Respiratory Medicine.
Commenting on these findings and those from the COVINTOC tocilizumab trial, Srinivas Murthy (University of British Columbia, Vancouver, Canada) and Todd Lee (McGill University, Montréal, Québec, Canada) say that they “add more pieces to the puzzle” on COVID-19 treatment strategies, and “need to be integrated with all the evidence available to establish the best strategies for patients around the world.”
Noting that the REMAP-CAP and RECOVERY trials demonstrated a reduction in mortality risk with IL-6 inhibitor treatment, they say that “the question will inevitably become which populations are most likely to benefit” from tocilizumab or sarilumab, and the absolute reduction in mortality risk “could vary considerably depending on the baseline risk of death.”
The commentators believe “it is vital that all trial teams urgently participate in a carefully planned meta-analysis, incorporating analyses for heterogeneous treatment effects and standardised subgroups, and focusing on the important clinical outcome of mortality.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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Lancet Respir Med 2021; doi:10.1016/S2213-2600(21)00099-0
Lancet Respir Med 2021; doi:10.1016/S2213-2600(21)00127-2