Anakinra
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Anakinra is a recombinant form of human interleukin-1 receptor antagonist used in the treatment of rheumatoid arthritis, neonatal-onset multisystem inflammatory disease and deficiency of interleukin-1 receptor antagonist (DIRA).
Anakinra is a recombinant form of human interleukin-1 receptor antagonist used in the treatment of rheumatoid arthritis, neonatal-onset multisystem inflammatory disease and deficiency of interleukin-1 receptor antagonist (DIRA).
Interleukin-1 (IL-1) plays an important role in inflammation and immunological responses. Inflammatory stimuli trigger its production, and it binds to the IL-1 receptor to activate a wide variety of mechanisms. The activity of the IL-1 receptor is also regulated by a naturally occurring IL-1 receptor antagonist (IL-1Ra) that competes for the binding sites of the IL-1 receptor. In rheumatoid arthritis (RA) patients, IL-1 levels are elevated, inducing cartilage degradation and the stimulation of bone resorption, and the amount of IL-1Ra in the synovium and synovial fluid of RA patients cannot compete with the high level of IL-1 present. Anakinra is a recombinant, non-glycosylated form of IL-1Ra that competes with and inhibits IL-1 by binding to the IL-1 receptor; therefore, the administration of this drug reduces the inflammatory response in RA patients. Anakinra can also be used in the treatment of neonatal-onset multisystem inflammatory disease (NOMID) and deficiency of interleukin-1 receptor antagonist (DIRA). Patients with NOMID have spontaneous mutations in CIAS1/NLRP3, a gene that encodes cryopyrin, an inflammasome component. When activated, the inflammasome enhances and promotes the production of IL-1β, an isoform of IL-1. DIRA is an autoinflammatory disease caused by mutations in the IL1RN gene. These mutations reduce the amount of IL-1Ra that is secreted, leading to the unopposed action of IL-1. Anakinra controls NOMID and DIRA symptoms by inhibiting IL-1 activity.
Anakinra is an interleukin-1 receptor antagonist indicated for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis (RA), in patients 18 years of age or older who have failed one or more disease-modifying antirheumatic drugs (DMARDs). Anakinra can be used alone or in combination with DMARDs other than Tumor Necrosis Factor (TNF) blocking agents. Anakinra is also indicated for the treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID) and the treatment of Deficiency of Interleukin-1 Receptor Antagonist (DIRA). Anakinra is also used off-label for the treatment of several inflammatory diseases. The FDA has issued an emergency use authorization (EUA) for the emergency use of anakinra for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults with positive results of direct SARS-CoV-2 viral testing with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR). Since anakinra is approved for this condition under EUA, the drug should only be used when there are no alternative treatment available.
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