Interleukin-1 (IL-1) inhibitors are a class of biologic therapies that block the activity of IL-1, a master pro-inflammatory cytokine that drives inflammation in autoinflammatory diseases, certain rheumatologic conditions, and other inflammatory disorders.
Three IL-1 inhibitors are currently FDA-approved: anakinra, canakinumab, and rilonacept.
Anakinra (Kineret) is a recombinant IL-1 receptor antagonist that binds to the IL-1 receptor and blocks signaling from both IL-1α and IL-1β.
It has a short half-life requiring daily subcutaneous injections and is FDA-approved for rheumatoid arthritis, neonatal-onset multisystem inflammatory disease (NOMID), and deficiency of interleukin-1 receptor antagonist (DIRA).
Canakinumab (Ilaris) is a human monoclonal antibody that selectively neutralizes IL-1β but not IL-1α.
Its long half-life permits subcutaneous dosing every 3 months.
It is FDA-approved for multiple conditions including cryopyrin-associated periodic syndromes (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS), [familial Mediterranean fever](/rare-disease/familial-mediterranean-fever) (FMF), Still’s disease (both adult-onset and systemic juvenile idiopathic arthritis), and gout flares.
Rilonacept (Arcalyst) is a recombinant fusion protein that binds to both IL-1α and IL-1β, with a relatively longer half-life than anakinra.
It is FDA-approved for CAPS and DIRA.
The American College of Rheumatology and European League Against Rheumatism recommend IL-1 targeted biologic therapy as the current standard of care for IL-1-mediated autoinflammatory diseases.
These agents have demonstrated rapid and sustained reduction in disease severity, including reversal of inflammation-mediated organ damage.