Anakinra Explained

Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a slightly modified recombinant version of the human interleukin 1 receptor antagonist protein. It is marketed by Swedish Orphan Biovitrum.[1] Anakinra is administered by subcutaneous injection.

Medical uses

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] It can be used in combination with some DMARDs.[1] [2] [3]

It is administered subcutaneously to patients diagnosed with a cryopyrin-associated periodic syndrome, including neonatal-onset multisystem inflammatory disease.[1] [2]

It is used to treat Schnitzler's syndrome (off label in the US).[4] Its response rate is such that it has been suggested that "Treatment failures should lead to reconsider the diagnosis."[5]

Off label, it is used to treat systemic juvenile idiopathic arthritis (SJIA), gout, calcium pyrophosphate deposition (CPPD), Behçet's disease, ankylosing spondylitis, uveitis, and other auto-inflammatory syndromes.[6]

In December 2021, the European Medicines Agency authorized the use of anakinra "to treat COVID-19 in 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."[7] [8] In November 2022, the United States FDA approved its use under an emergency 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)."[9] [10]

Safety

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, or who are taking TNF inhibitors.[2]

Adverse reactions

More than ten percent of people taking Anakinra have injection site reactions, headaches, and have increased cholesterol levels.[1] Recipients have eight percent more patients decrease white blood cells counts, two percent more patients decrease platelets counts, 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] [3]

Chemistry

Anakinra differs from the sequence of Interleukin 1 receptor antagonist by one methionine amino acid 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 approved for medical use in the US in 2001,[2] and in the European Union in 2002.[1]

In 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),[11] 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".[12]

In December 2020, Anakinra was approved by the US Food and Drug Administration for the treatment of deficiency of the interleukin-1–receptor antagonist (DIRA), a rare autoinflammatory disease of infancy.[13] In 2021, it was announced that the Ministry of Health of the Russian Federation had approved the use of Anakinra for the treatment of CAPS.[14]

In October 2021, NHS England published Clinical Commissioning Policy: Anakinra for Haemophagocytic Lymphohistiocytosis (HLH) for adults and children in all ages, allowing Anakinra to be used in the treatment of HLH.[15]

Society and culture

Legal status

Condition
CountryRACAPSFMFAOSDSchnitzler'sMKDTRAPSDIRAHLH
US20012020
UK20182018201820182021
EU200220022002
Russia2021

Research

Anakinra 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.[16] Researchers at Johns Hopkins University announced in 2019 that anakinra given to pregnant mice with Zika virus had reduced fetal deaths and birth defects.[17] 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.[18] [19]

In 2021, it was reported that Anakinra appeared to reduce the neuropathic pain experienced by patients undergoing chemotherapy with vincristine, saying that "repurposing anakinra may be an effective co-treatment strategy to prevent vincristine-induced peripheral neuropathy".[20] [21]

A review published in 2022 found that "Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Behçet's disease, Muckle–Wells syndrome, and SAPHO 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."[22]

In 2023, researchers at Columbia University explored the effect of Anakinra on the ageing of Hematopoietic stem cells in 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".[23] [24] [25]

A 2023 preliminary study on the use of Anakinra in the treatment of endometriosis concluded that "there is justification for a larger study" and that "Anakinra may be a particularly impactful option for women desiring fertility."[26]

COVID-19

Anakinra is undergoing multiple clinical trials to treat COVID-19 patients, by targeting mechanisms in patients with hyperinflammation.[27] In 2021 a review and meta-analysis of 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."[28]

, the European Medicines Agency (EMA) is evaluating an application to extend the use of anakinra to include treatment of COVID-19 in adults with pneumonia who are at risk of developing severe respiratory failure (inability of the lungs to work properly).[29] According to study results published in September 2021 in Nature Medicine, hospitalized COVID-19 patients at increased risk for respiratory failure showed significant improvement after treatment with Anakinra.[30] [31]

Notes and References

  1. Web site: Kineret 100 mg solution for injection in a pre-filled syringe - Summary of Product Characteristics (SmPC) . UK Electronic Medicines Compendium. 2 March 2022 .
  2. Web site: Kineret- anakinra injection, solution . DailyMed . 30 December 2020 . 2 March 2022.
  3. Singh JA, Hossain A, Tanjong Ghogomu E, Kotb A, Christensen R, Mudano AS, Maxwell LJ, Shah NP, Tugwell P, Wells GA . 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 . May 2016 . 27175934 . 7068903 . 10.1002/14651858.CD012183 .
  4. Gusdorf L, Lipsker D . Schnitzler Syndrome: a Review . Current Rheumatology Reports . 19 . 8 . 46 . August 2017 . 28718061 . 10.1007/s11926-017-0673-5 . 13780498 .
  5. Néel A, Henry B, Barbarot S, Masseau A, Perrin F, Bernier C, Kyndt X, Puechal X, Weiller PJ, Decaux O, Ninet J, Hot A, Aouba A, Astudillo L, Berthelot JM, Bonnet F, Brisseau JM, Cador B, Closs-Prophette F, Dejoie T, de Korwin JD, Dhote R, Fior R, Grosbois B, Hachulla E, Hatron PY, Jardel H, Launay D, Lorleac'h A, Pottier P, Moulis G, Serratrice J, Smail A, Hamidou M . Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: a French multicenter study . Autoimmunity Reviews . 13 . 10 . 1035–1041 . October 2014 . 25220180 . 10.1016/j.autrev.2014.08.031 .
  6. Web site: Anakinra (Kineret). 2021-11-22. American College of Rheumatology..
  7. Web site: EMA recommends approval for use of Kineret in adults with COVID-19 . European Medicines Agency . 16 December 2021 . 2 March 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. News: Aripaka P, Karimi A . EU regulator builds Omicron defences with approvals of GSK-Vir, Sobi drugs . 17 December 2021 . Reuters . 16 December 2021 .
  9. News: Sobi's Kineret granted FDA Emergency Use Authorisation for COVID-19 related pneumonia. PMNews. November 2022.
  10. Web site: FDA roundup. . November 15, 2022.
  11. Book: National Health Service (NHS) . England . Clinical Commissioning Policy: Anakinra to treat periodic fevers and autoinflammatory disorders (all ages) . 29 June 2018 . 9 July 2018.
  12. Book: National Health Service (NHS) . England . Clinical Commissioning Policy: Anakinra/tocilizumab for the treatment of Adult-Onset Still's Disease refractory to second-line therapy (adults) . 29 June 2018 . 13 July 2018 . 13 July 2018 . https://web.archive.org/web/20180713204934/https://www.england.nhs.uk/wp-content/uploads/2018/07/1609-anakinra-and-tocilizumab-for-aosd.pdf . dead .
  13. News: Kaufman MB . FDA Approves New Rituximab Biosimilar & Anakinra to Treat a Rare Disease . 4 February 2021 . The Rheumatologist . 2 February 2021.
  14. Web site: Kineret approved in Russia for the treatment of CAPS . The Pharma Letter . 18 February 2021 . 17 February 2021.
  15. Book: National Health Service (NHS) . England . Clinical Commissioning Policy: Anakinra for Haemophagocytic Lymphohistiocytosis (HLH) for adults and children in all ages . October 2021 . 14 October 2021 . 13 October 2021 . https://web.archive.org/web/20211013180802/https://www.england.nhs.uk/wp-content/uploads/2021/10/1924-Clinical-commissioning-policy-anakinra-for-haemophagocytic-lymphohistiocytosis-1.pdf . dead .
  16. News: When the Illness Is a Mystery, Patients Turn to These Detectives. Kolata G . 2019-01-07. The New York Times. 2019-01-09.
  17. News: Rheumatoid Arthritis Drug Diminishes Zika Birth Defects in Mice . 5 September 2019 . Newsroom . Johns Hopkins Medicine . 6 May 2019.
  18. News: Arthritis drugs could be repurposed to help prevent breast cancer spreading to the bone, study suggests . 21 November 2019 . Press release . University of Manchester . 20 November 2019.
  19. Eyre R, Alférez DG, Santiago-Gómez A, Spence K, McConnell JC, Hart C, Simões BM, Lefley D, Tulotta C, Storer J, Gurney A, Clarke N, Brown M, Howell SJ, Sims AH, Farnie G, Ottewell PD, Clarke RB . Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling . Nature Communications . 10 . 1 . 5016 . November 2019 . 31676788 . 6825219 . 10.1038/s41467-019-12807-0 . 2019NatCo..10.5016E .
  20. Starobova H, Monteleone M, Adolphe C, Batoon L, Sandrock CJ, Tay B, Deuis JR, Smith AV, Mueller A, Nadar EI, Lawrence GP, Mayor A, Tolson E, Levesque JP, Pettit AR, Wainwright BJ, Schroder K, Vetter I . Vincristine-induced peripheral neuropathy is driven by canonical NLRP3 activation and IL-1β release . The Journal of Experimental Medicine . 218 . 5 . e20201452 . May 2021 . 33656514 . 7933984 . 10.1084/jem.20201452 .
  21. Web site: Chemotherapy with fewer side effects may be on the way . University of Queensland . 15 March 2021 . 15 March 2021.
  22. Tegtmeyer K, Atassi G, Zhao J, Maloney NJ, Lio PA . Off-Label studies on anakinra in dermatology: a review . The Journal of Dermatological Treatment . 33 . 1 . 73–86 . February 2022 . 32279586 . 10.1080/09546634.2020.1755417 . 215749189 .
  23. News: Caler L . This Arthritis Drug Could Rejuvenate Blood In The Elderly, Delay Aging . 6 February 2023 . Medical Daily . 1 February 2023 . en.
  24. Mitchell CA, Verovskaya EV, Calero-Nieto FJ, Olson OC, Swann JW, Wang X, Hérault A, Dellorusso PV, Zhang SY, Svendsen AF, Pietras EM, Bakker ST, Ho TT, Göttgens B, Passegué E . Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing . Nature Cell Biology . 25 . 1 . 30–41 . January 2023 . 36650381 . 10.1038/s41556-022-01053-0 . 7614279 .
  25. News: Arthritis drug mimics "young blood" transfusions to reverse aging in mice. Irving M . 6 February 2023 . New Atlas. 6 February 2023.
  26. Sullender R, Agarwal R, Jacobs M, Valentine H, Foster L, Agarwal SK . 10217 IL-1 Antagonist Anakinra for the Treatment of Endometriosis: A Placebo Controlled, Randomized Pilot Study . Journal of Minimally Invasive Gynecology . November 2023 . 30 . 11 . S107 . 10.1016/j.jmig.2023.08.342. 264540594 .
  27. News: Anakinra in COVID-19: important considerations for clinical trials . 5 January 2021 . Press release . May 2020.
  28. Barkas F, Filippas-Ntekouan S, Kosmidou M, Liberopoulos E, Liontos A, Milionis H . Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis . Rheumatology . 60 . 12 . 5527–5537 . December 2021 . 33999135 . 8194671 . 10.1093/rheumatology/keab447 .
  29. EMA starts evaluating the use of Kineret in adult COVID-19 patients at increased risk severe respiratory failure . European Medicines Agency (EMA) . 16 July 2021 . 20 July 2021.
  30. Kyriazopoulou E, Poulakou G, Milionis H, Metallidis S, Adamis G, Tsiakos K, Fragkou A, Rapti A, Damoulari C, Fantoni M, Kalomenidis I, Chrysos G, Angheben A, Kainis I, Alexiou Z, Castelli F, Serino FS, Tsilika M, Bakakos P, Nicastri E, Tzavara V, Kostis E, Dagna L, Koufargyris P, Dimakou K, Savvanis S, Tzatzagou G, Chini M, Cavalli G, Bassetti M, Katrini K, Kotsis V, Tsoukalas G, Selmi C, Bliziotis I, Samarkos M, Doumas M, Ktena S, Masgala A, Papanikolaou I, Kosmidou M, Myrodia DM, Argyraki A, Cardellino CS, Koliakou K, Katsigianni EI, Rapti V, Giannitsioti E, Cingolani A, Micha S, Akinosoglou K, Liatsis-Douvitsas O, Symbardi S, Gatselis N, Mouktaroudi M, Ippolito G, Florou E, Kotsaki A, Netea MG, Eugen-Olsen J, Kyprianou M, Panagopoulos P, Dalekos GN, Giamarellos-Bourboulis EJ . 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 . October 2021 . 34480127 . 8516650 . 10.1038/s41591-021-01499-z . free .
  31. Web site: Anakinra improved survival in hospitalized COVID-19 patients. 2021-09-09. www.mdedge.com.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Anakinra".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.