Background:Off-label intravenous (IV) route of anakinra is increasingly recognized to enable higher and faster maximal plasma concentrations than subcutaneous route for treatment of cytokine storm syndromes.Objective:To describe off-label indications of IV anakinra, corresponding dosing and safety profiles, particularly during the coronavirus disease 19 (COVID-19) pandemic.Methods:A retrospective, single-cohort study was conducted at an academic medical center to evaluate use of IV anakinra in hospitalized pediatric patients (age ≤21 years). Institutional Review Board review was considered exempt. The primary endpoint was the primary indication(s) for IV anakinra. The key secondary endpoints were dosing of IV anakinra, previous immunomodulatory therapies, and adverse events.Results:Of 14 pediatric patients, 8 (57.1%) received IV anakinra for treatment of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, whereas 3 and 2 were treated for hemophagocytic lymphohistiocytosis (HLH) and flares of systemic onset juvenile idiopathic arthritis (SoJIA), respectively. The initial dosing regimen of IV anakinra for MIS-C associated with COVID-19 was a median dose of 2.25 mg/kg/dose with a median dosing interval of 12 hours for a median initial treatment duration of 3.5 days. Eleven (78.6%) patients received previous immunomodulatory therapies (IV immune globulin [n = 10; 71.4%] and steroids [n = 9; 64.3%]). No adverse drug events were documented.Conclusion:IV anakinra was used off-label for treatment of MIS-C associated with COVID-19, HLH and SoJIA flares in critically ill patients with no adverse drug events documented. This study helped ascertain the off-label indications of IV anakinra and corresponding patient characteristics.