COVID-19 Curbside Consults

Cytokine release syndrome and the prospects for immunotherapy with COVID-19. Part 2: The role of interleukin 1

Leonard H. Calabrese, DO and Cassandra Calabrese, DO
Cleveland Clinic Journal of Medicine July 2020, DOI: https://doi.org/10.3949/ccjm.87a.ccc044

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  • TABLE 1

    Currently available interleukin 1 inhibitors

    AgentMechanism of actionCurrent FDA-approved indications and dosingContraindications and cautions
    Anakinra (Kineret)Recombinant human IL-1 receptor antagonist
    Inhibits activity of IL-1 alpha and IL-1 beta    		Rheumatoid arthritis: 100 mg subcutaneously once a day
    CAPS/NOMID: 1-2 mg/kg subcutaneously once a day; can increase by 0.5-1 mg/kg increments; maximum dose 8 mg/kg
    Renal dosing: if creatinine clearance is < 30 mL/min or patient is in end-stage renal disease, consider alternate dosing    		Use with caution in patients with:
    Concomitant TNF inhibitor use
    Serious active infection
    Neutropenia
    Canakinumab (Ilaris)Human monoclonal anti-IL-1 beta
    Neutralizes IL-1 beta activity    		Systemic juvenile idiopathic arthritis: 4 mg/kg subcutaneously once a month; not to exceed 300 mg/dose (≥ 2 years and weight ≥ 7.5 kg)
    CAPS: If 15-40 kg, 2 mg/kg subcutaneously every 8 weeks
    If ≥ 40 kg, 150 mg subcutaneously every 8 weeks
    FMF, TRAPS and HIDS/MVD: If ≤ 40 kg, 2 mg/kg subcutaneously every 4 weeks, can increase to 4 mg/kg every 4 weeks
    If > 40 kg, 150 mg subcutaneously every 4 weeks; can increase to 300 mg every 4 weeks    		Use with caution in patients with serious active infection
    Rilonacept (Arcalyst)Fusion protein of extracellular domains of IL-1-RAcP and IL-1-R1 fused to FC portion of human IgG1
    Binds to IL-1 alpha and IL-1 beta to block IL-1 signaling    		CAPS:
    Adults—loading dose 320 mg subcutaneously, followed by 160 mg subcutaneously weekly
    Children (12-17 years)—loading dose of 4.4 mg/kg (maximum dose 320 mg), followed by 2.2 mg/kg subcutaneously weekly (maximum dose 160 mg)    		Use with caution in patients with serious active infection

    • CAPS = cryopyrin-associated periodic syndromes; FC = fragment crystallizable; FMF = familial Mediterranean fever, HIDS/MKD = hyperimmunoglobulin D syndrome/mevalonate kinase deficiency; IG = immunoglobulin; IL = interleukin; IL-1-RAcP = IL-1 receptor accessory protein; IL-1-R1 = interleukin 1 receptor, type I; NOMID = neonatal-onset multisystem inflammatory disease; TNF = tumor necrosis factor; TRAPS = tumor necrosis factor receptor associated periodic syndrome

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