Among patients with moderate to severe COVID-19 pneumonia, treatment with sarilumab did not improve early outcomes, according to study results published in Lancet Rheumatology.
Researchers conducted an open-label, Bayesian randomized, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort (ClinicalTrials.gov Identifier: NCT04324073) to evaluate the effect of sarilumab on outcomes of COVID-19 pneumonia.
Primary study outcomes were the percentage of patients with World Health Organization Clinical Progression Scale (WHO-CPS) scores of greater than 5 on a 10-point scale on day 4 and survival without invasive or noninvasive ventilation at day 14.
Adult patients were enrolled in the study from 6 centers in France. Patients were required to have at least 3 L/min of oxygen, but not ventilation assistance, and a WHO-CPS score of at least 5. Patients were randomly assigned to a sarilumab group receiving standard care plus 400 mg of sarilumab intravenously on day 1, and on day 3 if clinically indicated, or a standard-care alone group.
The study outcome was the percentage of patients with WHO-CPS scores greater than 5 on day 4 and survival without invasive or noninvasive ventilation at day 14.
Of 165 patients enrolled between March and April 2020, 148 were selected for the study and followed-up with for 90 days. The sarilumab group had 68 patients and the standard-care group had 80 patients, of whom 4 withdrew consent and excluded from the analysis.
At day 4, the number of patients with a WHO-CPS score greater than 5 in the sarilumab and standard-care groups were 26% each (n=18 and 20, respectively; median posterior absolute risk difference, 0.2%; 90% credible interval [CrI], -11.7% to 12.2%). A posterior probability of absolute risk difference greater than 0 of 48.9% were noted.
At day 14, the number of patients needing ventilation or who had died were 25 (37%) patients in the sarilumab group and 26 (34%) patients in the standard-care group (median posterior hazard ratio [HR], 1.10; 90% CrI, 0.69-1.74). A posterior probability HR of greater than 1 of 37.4% were observed.
Serious adverse events were reported in 27 (40%) and 28 (37%) patients in the sarilumab and standard-care groups, respectively (P =.73).
Study limitations included a small sample size that was designed to detect a large drug effect, lack of blinding, an imbalance in the group sizes, potential differences in the standard-care group across centers and over time, and that results may not be generalizable to the entire COVID-19 population. Unblinding may have also led to a performance bias in the sarilumab group. An additional study limitation was the infrequent use of dexamethasone.
According to the researchers, “Larger [randomized] controlled trials with longer follow-up, as well as meta-analyses, are needed for determining the exact effects of sarilumab and other [interleukin] (IL)-6 receptor antagonists in different subsets of patients, and whether combined therapy with dexamethasone might further improve outcomes.”
Mariette X, Hermine O, Tharaux PL, et al. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial. Lancet Rheumatol. 2022;4(1):e24-e32. doi:10.1016/S2665-9913(21)00315-5