Anakinra

Anakinra (brand name Kineret) is a biopharmaceutical drug used to treat rheumatoid arthritis. It is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein. It is marketed by Swedish Orphan Biovitrum.[1]

Anakinra
Clinical data
Trade namesKineret
AHFS/Drugs.comMonograph
MedlinePlusa602001
License data
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
    Routes of
    administration
    Subcutaneous
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability95%
    Metabolismpredominantly renal
    Elimination half-life4-6 hrs
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    UNII
    KEGG
    ChEMBL
    Chemical and physical data
    FormulaC759H1186N208O232S10
    Molar mass17,257.6 g/mol g·mol−1
     NY (what is this?)  (verify)

    Medical use

    Anakinra is administered at home by subcutaneous injection.[2]

    It is used as a second line treatment to manage symptoms of rheumatoid arthritis after treatment with a disease-modifying antirheumatic drug (DMARD) has failed.[1][2] It can be used in combination with some DMARDs.[1][2][3]

    It is used to treat anyone from infants to adults with a cryopyrin-associated periodic syndrome, including neonatal-onset multisystem inflammatory disease.[1][2]

    It is used off label to treat Schnitzler's syndrome.[4]

    It was not tested in pregnant women, but appeared to be safe in animal studies.[2]

    It should not be used in people who have active infections or latent tuberculosis, who have low white blood cells counts, or who are taking TNF inhibitors.[2]

    Adverse effects

    More than ten percent of people taking Anakinra have injection site reactions, headaches, and have increased levels of cholesterol in their blood.[1] Between one and ten percent of people have severe infections, decreased white blood cells, or decreased platelets.[1] It is unclear if taking Anakinra increases the risk of getting cancer; studies are complicated by the fact that people with rheumatoid arthritis are already at higher risk of getting cancer.[1][3]

    Chemistry

    Anakinra is a protein that differs from the sequence of Interleukin 1 receptor antagonist by one methionine added to its N-terminus; it also differs from the human protein in that it is not glycosylated, as it is manufactured in Escherichia coli.[2]

    History

    It was first approved in the US in 2001[2] and Europe in March 2002.[1]

    In June 2018 NHS England published a Clinical Commissioning Policy: Anakinra to treat periodic fevers and autoinflammatory disorders (all ages) allowing Anakinra to be commissioned as a first-line treatment for Schnitzler's syndrome and in cases where the first-line treatment is not effective for Familial Mediterranean fever, Hyper-IgD syndrome also known as Mevalonate kinase deficiency, and TNF receptor associated periodic syndrome (TRAPS),[5] and a Clinical Commissioning Policy: Anakinra/tocilizumab for the treatment of Adult-Onset Still's Disease refractory to second-line therapy (adults), allowing Anakinra to be commissioned for Adult-onset Still's disease "as a third line treatment where patients are refractory to steroid-sparing effect DMARDs".[6]

    Anakira effectively treated meningitis caused by a rare genetic mutation in the gene NALP3 in a 67-year-old man enrolled in the Undiagnosed Diseases Network.[7] Researchers at Johns Hopkins University announced in 2019 that anakinra given to pregnant mice with Zika virus had reduced fetal deaths and birth defects.[8] In November 2019 researchers at the University of Manchester reported that Anakinra might have a use in preventing breast cancer from spreading to the bones.[9][10]

    References

    1. "UK Anakinra label". UK Electronic Medicines Compendium. 5 October 2017. Retrieved 23 March 2018.
    2. "US Anakinra label" (PDF). FDA. May 2016. Retrieved 23 March 2018. For label updates see FDA index page for BLA 103950
    3. Singh, JA; Hossain, A; Tanjong Ghogomu, E; Kotb, A; Christensen, R; Mudano, AS; Maxwell, LJ; Shah, NP; Tugwell, P; Wells, GA (13 May 2016). "Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis". The Cochrane Database of Systematic Reviews (5): CD012183. doi:10.1002/14651858.CD012183. PMID 27175934.
    4. Gusdorf, L; Lipsker, D (August 2017). "Schnitzler Syndrome: a Review". Current Rheumatology Reports. 19 (8): 46. doi:10.1007/s11926-017-0673-5. PMID 28718061.
    5. NHS England (29 June 2018). Clinical Commissioning Policy: Anakinra to treat periodic fevers and autoinflammatory disorders (all ages) (PDF). Retrieved 9 July 2018.
    6. NHS England (29 June 2018). Clinical Commissioning Policy: Anakinra/tocilizumab for the treatment of Adult-Onset Still's Disease refractory to second-line therapy (adults) (PDF). Retrieved 13 July 2018.
    7. Kolata, Gina (2019-01-07). "When the Illness Is a Mystery, Patients Turn to These Detectives". The New York Times. ISSN 0362-4331. Retrieved 2019-01-09.
    8. "Rheumatoid Arthritis Drug Diminishes Zika Birth Defects in Mice". Newsroom. Johns Hopkins Medicine. 6 May 2019. Retrieved 5 September 2019.
    9. "Arthritis drugs could be repurposed to help prevent breast cancer spreading to the bone, study suggests". Press release. University of Manchester. 20 November 2019. Retrieved 21 November 2019.
    10. Eyre, Rachel; Alférez, Denis G.; Santiago-Gómez, Angélica; Spence, Kath; McConnell, James C.; Hart, Claire; Simões, Bruno M.; Lefley, Diane; Tulotta, Claudia; Storer, Joanna; Gurney, Austin; Clarke, Noel; Brown, Mick; Howell, Sacha J.; Sims, Andrew H.; Farnie, Gillian; Ottewell, Penelope D.; Clarke, Robert B. (1 November 2019). "Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling". Nature Communications. 10 (1): 5016. doi:10.1038/s41467-019-12807-0. PMC 6825219. PMID 31676788.
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