Efficacy and Safety of Sarilumab in Hospitalized Patients With Coronavirus Disease 2019: A Randomized Clinical Trial

Abstract

Background: Open-label platform trials and a prospective meta-analysis suggest efficacy of anti-interleukin (IL)-6R therapies in hospitalized patients with coronavirus disease 2019 (COVID-19) receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti-IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19.

Methods: In this adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial, adults hospitalized with COVID-19 received intravenous sarilumab 400 mg or placebo. The phase 3 primary analysis population included patients with critical COVID-19 receiving mechanical ventilation (MV). The primary outcome was proportion of patients with ≥1-point improvement in clinical status from baseline to day 22.

Results: There were 457 and 1365 patients randomized and treated in phases 2 and 3, respectively. In phase 3, patients with critical COVID-19 receiving MV (n = 298; 28.2% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive, not receiving MV) at day 22 was 43.2% for sarilumab and 35.5% for placebo (risk difference, +7.5%; 95% confidence interval [CI], -7.4 to 21.3; P =.3261), a relative risk improvement of 21.7%. In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio for death for sarilumab vs placebo was 0.76 (95% CI, .51 to 1.13) overall and 0.49 (95% CI, .25 to .94) in patients receiving corticosteroids at baseline.

Conclusions: This study did not establish the efficacy of sarilumab in hospitalized patients with severe/critical COVID-19. Post hoc analyses were consistent with other studies that found a benefit of sarilumab in patients receiving corticosteroids.

Clinical trials registration: NCT04315298.

Keywords: COVID-19; hospitalized; interleukin-6 receptor; monoclonal antibodies.

Figure 1.

Phase 3, cohort 1: flow diagram. ^* Includes 9 screen failures that were randomized.

Figure 2.

Improvement in clinical status and risk of death in phase 3, cohort 1. A, Risk difference for various population strata achieving ≥1-point improvement in clinical status from baseline to day 22 using the 7-point ordinal scale. B, Hazard ratios for the risk of death in various population strata. C, Hazard ratios for the risk of death in various population strata by steroid use. ^aUnstratified analysis. ^bKey secondary end point for phase 3, cohort 1. ^cPrimary end point for phase 3, cohort 1. ^dHazard ratio could not be calculated, as the number of events was too small. Abbreviations: CI, confidence interval; EITT, exploratory intention to treat; ITT, intention to treat; IV, intravenous; MSOD, multisystemic organ dysfunction.

Figure 3.

Kaplan-Meier curve of time to death in phase 3, cohort 1. A, Severe patients (exploratory intention-to-treat [ITT] population). B, Critical patients on mechanical ventilation at baseline (ITT population). C, Critical patients not on mechanical ventilation at baseline (ITT population). Abbreviation: IV, intravenous.