SARILUMAB PLUS STANDARD of CARE (SOC) VERSUS SOC for SEVERE COVID-19 (ESCAPE STUDY)

ABSTRACT

Background: We aimed to evaluate the efficacy of sarilumab, an IL-6 receptor inhibitor, combined with SOC, in patients (pts) affected by severe COVID-19 pneumonia. Methods: Open-label, Phase III, randomized trial assessing clinical efficacy and safety of intravenous sarilumab in pts with severe COVID-19, at 5 clinical centers in Italy. We included hospitalized pts with SARS-CoV-2 infection and pneumonia, in severe or critical condition (excluding mechanically ventilated). Pts were randomized 21 to receive sarilumab 400 mg plus SOC (armA) or to continue SOC (armB). The primary endpoint was time to clinical improvement of 2 points on a 7-point category ordinal scale, ranging from 1 (discharged with resumption of normal activities) to 7 (death). Pts were stratified according to baseline disease severity (PaO2/FiO2 ratio < or ≥ 200 mmHg), C reactive protein (CRP < or ≥ 7 mg/dL) and lymphocytes count (< or ≥ 870/mmc). The key secondary endpoint was time to death. Adverse events (AE) were evaluated as safety outcomes. We used chi square test to compare proportions between arms, and Cox regression stratified by clinical center to estimate the hazard risk (HR) of primary endpoint. Results: Of 191 pts screened, 176 were assigned to armA (121) and B (55). A similar proportion of pts were treated with steroids (44 armA vs 26 armB, p=0.170) and remdesivir (22 armA vs 8 armB, p=0.552). 58/121 (48%) pts underwent to a second dose of sarilumab 12 hours after the first dose. At day 30, no significant differences in the primary endpoint were found between the arms (Figure1). After stratifying for inflammatory parameters, the probability of improvement seemed greater in armA than B, for the strata with CRP <7 mg/dL (88% [95% CI 77-96] vs 79% [63-91], HR 1.55 [0.9-2.6];log-rank p=0.049) and with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7];log-rank p=0.058). Figure2 for interaction tests between strata. There were no significant differences in death probability (armA 5% [2.3-10.9]) and armB 3.6% [0.9-13.8] HR 1.30 [0.41-4.15];log-rank p=0.79) and in the rates of AE (armA 32% [39/121] and armB 23% [14/55], p=0.195) and serious AE (armA 18% [22/121] and armB 11% [7/55], p=0.244). Conclusion: In our population, efficacy of sarilumab in pts with severe COVID-19 was not confirmed, even if some benefits were shown in those treated at an early stage of the disease with lower inflammatory burden. Further trials are needed for identifying targeted subgroups for maximizing benefit of this treatment.