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Anakinra

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Anakinra
Clinical data
Trade namesKineret
AHFS/DrugsMonograph
MedlinePlusa602001
License data
Pregnancy
category
  • AU:B1
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
Pharmacokineticdata
Bioavailability95%
Metabolismpredominantly kidney
Eliminationhalf-life4-6 hrs
Identifiers
  • Recombinant human Interleukin-1 receptor antagonist protein; syn. N2-l-methionyl-interleukin 1 receptor antagonist (human isoform x reduced)
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC759H1186N208O232S10
Molar mass17257.66g·mol−1
☒NcheckY(what is this?)(verify)

Anakinra,sold under the brand nameKineret,is abiopharmaceuticalmedication used to treatrheumatoid arthritis,cryopyrin-associated periodic syndromes,familial Mediterranean fever,andStill's disease.[3]It is a slightly modifiedrecombinantversion of the humaninterleukin 1 receptor antagonistprotein.[3]It is marketed bySwedish Orphan Biovitrum.[1]Anakinra is administered bysubcutaneous injection.[2]

Medical uses

[edit]

It is used as a second line treatment to manage symptoms of rheumatoid arthritis after treatment with adisease-modifying antirheumatic drug(DMARD) has failed.[1][2]It can be used in combination with some DMARDs.[1][2][4]

It is administered subcutaneously to patients diagnosed with acryopyrin-associated periodic syndrome,includingneonatal-onset multisystem inflammatory disease.[1][2]

It is used to treatSchnitzler's syndrome(off label in the US).[5]Its response rate is such that it has been suggested that "Treatment failures should lead to reconsider the diagnosis."[6]

Off label,it is used to treatsystemic juvenile idiopathic arthritis(SJIA),gout,calcium pyrophosphate deposition(CPPD),Behçet's disease,ankylosing spondylitis,uveitis,and otherauto-inflammatory syndromes.[7]

In December 2021, theEuropean Medicines Agencyauthorized the use of anakinra "to treatCOVID-19in adults with pneumonia requiring supplemental oxygen (low or high flow oxygen) and who are at risk of developing severe respiratory failure, as determined by blood levels of a protein called suPAR (soluble urokinase plasminogen activator receptor) of at least 6 ng per ml. "[3][8][9]In November 2022, the United StatesFDAapproved its use under anemergency use authorization"for the treatment of COVID-19 in hospitalized adults 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)."[10][11]

Safety

[edit]

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[clarification needed]or latent tuberculosis, or who are takingTNF inhibitors.[2]

Adverse reactions

[edit]

More than ten percent of people taking Anakinra haveinjection site reactions,headaches, and have increased cholesterol levels.[1]Recipients have eight percent more patients decreasewhite blood cellscounts, two percent more patients decreaseplateletscounts, one percent more patients get severe infections (4.5% for patients with asthma compared to 0% placebo patients with asthma).[1]It is unclear if taking Anakinra increases cancer risk; studies are complicated by the fact that people with rheumatoid arthritis already face higher cancer risk.[1][4]

Chemistry

[edit]

Anakinra differs from the sequence ofInterleukin 1 receptor antagonistby onemethionineamino acidadded to itsN-terminus;it also differs from the human protein in that it is notglycosylated,as it ismanufacturedinEscherichia coli.[2]

History

[edit]

It was approved for medical use in the US in 2001,[2]and in the European Union in 2002.[1][3]

In 2018,NHS Englandpublished aClinical Commissioning Policy: Anakinra to treat periodic fevers and autoinflammatory disorders (all ages)allowing Anakinra to be commissioned as a first-line treatment forSchnitzler's syndromeand in cases where the first-line treatment is not effective for Familial Mediterranean fever,Hyper-IgD syndromealso known asMevalonate kinase deficiency,andTNF receptor associated periodic syndrome(TRAPS),[12]and aClinical 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".[13]

In December 2020, Anakinra was approved by the USFood and Drug Administrationfor the treatment ofdeficiency of the interleukin-1–receptor antagonist(DIRA), a rare autoinflammatory disease of infancy.[14]In 2021, it was announced that theMinistry of Health of the Russian Federationhad approved the use of Anakinra for the treatment ofCAPS.[15]

In October 2021, NHS England publishedClinical Commissioning Policy: Anakinra for Haemophagocytic Lymphohistiocytosis (HLH) for adults and children in all ages,allowing Anakinra to be used in the treatment ofHLH.[16]

Society and culture

[edit]
[edit]
Approvals
Condition
Country RA CAPS FMF AOSD Schnitzler's MKD TRAPS DIRA HLH
US 2001 2020
UK 2018 2018 2018 2018 2021
EU 2002 2002 2002
Russia 2021

Research

[edit]

Anakinra effectively treated meningitis caused by a rare genetic mutation in the geneNALP3in a 67-year-old man enrolled in theUndiagnosed Diseases Network.[17]Researchers atJohns Hopkins Universityannounced in 2019 that anakinra given to pregnant mice withZika virushad reduced fetal deaths and birth defects.[18]In November 2019, researchers at theUniversity of Manchesterreported that Anakinra might have a use in preventing breast cancer from spreading to the bones.[19][20]

In 2021, it was reported that Anakinra appeared to reduce theneuropathic painexperienced by patients undergoingchemotherapywithvincristine,saying that "repurposing anakinra may be an effective co-treatment strategy to prevent vincristine-induced peripheral neuropathy".[21][22]

A review published in 2022 found that "Anakinra appears to show efficacy for numerousdermatologicconditions, with the strongest evidence forhidradenitis suppurativa,Behçet's disease,Muckle–Wells syndrome,andSAPHO syndrome."and concluded that" Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role. "[23]

In 2023, researchers atColumbia Universityexplored the effect of Anakinra on the ageing ofHematopoietic stem cellsin mice. They concluded "that targeting IL-1 as a key mediator of niche inflammation is a tractable strategy to improve blood production during ageing" and were reported to have said "that their findings could pave the way for science to delay aging and even lengthen the lifespan of humans".[24][25][26]

A 2023 preliminary study on the use of Anakinra in the treatment ofendometriosisconcluded that "there is justification for a larger study" and that "Anakinra may be a particularly impactful option for women desiring fertility."[27]

COVID-19

[edit]

Anakinra is undergoing multiple clinical trials to treatCOVID-19patients, by targeting mechanisms in patients with hyperinflammation.[28]In 2021 a review andmeta-analysisof 9 studies involving 1,119 cases concluded that "Available evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events."[29]

As of July 2021,theEuropean Medicines Agency(EMA) is evaluating an application to extend the use of anakinra to include treatment ofCOVID-19in adults with pneumonia who are at risk of developing severe respiratory failure (inability of the lungs to work properly).[30]According to study results published in September 2021 inNature Medicine,hospitalized COVID-19 patients at increased risk forrespiratory failureshowed significant improvement after treatment with Anakinra.[31][32]

References

[edit]
  1. ^abcdefghi"Kineret 100 mg solution for injection in a pre-filled syringe - Summary of Product Characteristics (SmPC)".UK Electronic Medicines Compendium.Retrieved2 March2022.
  2. ^abcdefghi"Kineret- anakinra injection, solution".DailyMed.30 December 2020.Retrieved2 March2022.
  3. ^abcde"Kineret EPAR".European Medicines Agency.17 September 2018.Retrieved20 July2021.Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. ^abSingh JA, Hossain A, Tanjong Ghogomu E, Kotb A, Christensen R, Mudano AS, et al. (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.2016(5): CD012183.doi:10.1002/14651858.CD012183.PMC7068903.PMID27175934.
  5. ^Gusdorf L, Lipsker D (August 2017). "Schnitzler Syndrome: a Review".Current Rheumatology Reports.19(8): 46.doi:10.1007/s11926-017-0673-5.PMID28718061.S2CID13780498.
  6. ^Néel A, Henry B, Barbarot S, Masseau A, Perrin F, Bernier C, et al. (October 2014)."Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: a French multicenter study"(PDF).Autoimmunity Reviews.13(10): 1035–1041.doi:10.1016/j.autrev.2014.08.031.PMID25220180.
  7. ^"Anakinra (Kineret)".American College of Rheumatology.Retrieved2021-11-22.
  8. ^"EMA recommends approval for use of Kineret in adults with COVID-19".European Medicines Agency.16 December 2021.Retrieved2 March2022.Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. ^Aripaka P, Karimi A (16 December 2021)."EU regulator builds Omicron defences with approvals of GSK-Vir, Sobi drugs".Reuters.Retrieved17 December2021.
  10. ^"Sobi's Kineret granted FDA Emergency Use Authorisation for COVID-19 related pneumonia".PMNews.November 2022.
  11. ^"FDA roundup".Food and Drug Administration.November 15, 2022.
  12. ^Clinical Commissioning Policy: Anakinra to treat periodic fevers and autoinflammatory disorders (all ages)(PDF).England: National Health Service (NHS). 29 June 2018.Retrieved9 July2018.
  13. ^Clinical Commissioning Policy: Anakinra/tocilizumab for the treatment of Adult-Onset Still's Disease refractory to second-line therapy (adults)(PDF).England: National Health Service (NHS). 29 June 2018. Archived fromthe original(PDF)on 13 July 2018.Retrieved13 July2018.
  14. ^Kaufman MB (2 February 2021)."FDA Approves New Rituximab Biosimilar & Anakinra to Treat a Rare Disease".The Rheumatologist.Retrieved4 February2021.
  15. ^"Kineret approved in Russia for the treatment of CAPS".The Pharma Letter.17 February 2021.Retrieved18 February2021.
  16. ^Clinical Commissioning Policy: Anakinra for Haemophagocytic Lymphohistiocytosis (HLH) for adults and children in all ages(PDF).England: National Health Service (NHS). October 2021. Archived fromthe original(PDF)on 13 October 2021.Retrieved14 October2021.
  17. ^Kolata G (2019-01-07)."When the Illness Is a Mystery, Patients Turn to These Detectives".The New York Times.Retrieved2019-01-09.
  18. ^"Rheumatoid Arthritis Drug Diminishes Zika Birth Defects in Mice".Newsroom.Johns Hopkins Medicine. 6 May 2019.Retrieved5 September2019.
  19. ^"Arthritis drugs could be repurposed to help prevent breast cancer spreading to the bone, study suggests".Press release.University of Manchester. 20 November 2019.Retrieved21 November2019.
  20. ^Eyre R, Alférez DG, Santiago-Gómez A, Spence K, McConnell JC, Hart C, et al. (November 2019)."Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling".Nature Communications.10(1): 5016.Bibcode:2019NatCo..10.5016E.doi:10.1038/s41467-019-12807-0.PMC6825219.PMID31676788.
  21. ^Starobova H, Monteleone M, Adolphe C, Batoon L, Sandrock CJ, Tay B, et al. (May 2021)."Vincristine-induced peripheral neuropathy is driven by canonical NLRP3 activation and IL-1β release".The Journal of Experimental Medicine.218(5): e20201452.doi:10.1084/jem.20201452.PMC7933984.PMID33656514.
  22. ^"Chemotherapy with fewer side effects may be on the way".University of Queensland. 15 March 2021.Retrieved15 March2021.
  23. ^Tegtmeyer K, Atassi G, Zhao J, Maloney NJ, Lio PA (February 2022). "Off-Label studies on anakinra in dermatology: a review".The Journal of Dermatological Treatment.33(1): 73–86.doi:10.1080/09546634.2020.1755417.PMID32279586.S2CID215749189.
  24. ^Caler L (1 February 2023)."This Arthritis Drug Could Rejuvenate Blood In The Elderly, Delay Aging".Medical Daily.Retrieved6 February2023.
  25. ^Mitchell CA, Verovskaya EV, Calero-Nieto FJ, Olson OC, Swann JW, Wang X, et al. (January 2023)."Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing".Nature Cell Biology.25(1): 30–41.doi:10.1038/s41556-022-01053-0.PMC7614279.PMID36650381.
  26. ^Irving M (6 February 2023)."Arthritis drug mimics" young blood "transfusions to reverse aging in mice".New Atlas.Retrieved6 February2023.
  27. ^Sullender R, Agarwal R, Jacobs M, Valentine H, Foster L, Agarwal SK (November 2023). "10217 IL-1 Antagonist Anakinra for the Treatment of Endometriosis: A Placebo Controlled, Randomized Pilot Study".Journal of Minimally Invasive Gynecology.30(11): S107.doi:10.1016/j.jmig.2023.08.342.S2CID264540594.
  28. ^"Anakinra in COVID-19: important considerations for clinical trials".Press release.May 2020.Retrieved5 January2021.
  29. ^Barkas F, Filippas-Ntekouan S, Kosmidou M, Liberopoulos E, Liontos A, Milionis H (December 2021)."Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis".Rheumatology.60(12): 5527–5537.doi:10.1093/rheumatology/keab447.PMC8194671.PMID33999135.
  30. ^"EMA starts evaluating the use of Kineret in adult COVID-19 patients at increased risk severe respiratory failure".European Medicines Agency(EMA)(Press release). 16 July 2021.Retrieved20 July2021.
  31. ^Kyriazopoulou E, Poulakou G, Milionis H, Metallidis S, Adamis G, Tsiakos K, et al. (October 2021)."Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial".Nature Medicine.27(10): 1752–1760.doi:10.1038/s41591-021-01499-z.PMC8516650.PMID34480127.
  32. ^"Anakinra improved survival in hospitalized COVID-19 patients".mdedge.Retrieved2021-09-09.
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