Misplaced Pages

Anakinra: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively
Page 1
Page 2
← Previous editContent deleted Content addedVisualWikitext
Revision as of 12:46, 28 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit Latest revision as of 05:31, 21 October 2024 edit undo1AmNobody24 (talk | contribs)Edit filter helpers, Extended confirmed users, Pending changes reviewers, Rollbackers21,708 editsm added link(s) to Journal of Minimally Invasive Gynecology (via WP:JWB) 
(209 intermediate revisions by 91 users not shown)
Line 1: Line 1:
{{Short description|Pharmaceutical drug}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox {{Drugbox
| Verifiedfields = changed
| IUPAC_name = Recombinant human Interleukin-1 receptor antagonist protein; syn. N2-l-methionyl-interleukin 1 receptor antagonist (human isoform x reduced)
| verifiedrevid = 457810558
| image = Anakinra.png | image = Anakinra.png
| width = 220 | width = 220
| alt =


<!--Clinical data--> <!-- Clinical data -->
| pronounce =
| tradename = Kineret | tradename = Kineret
| Drugs.com = {{drugs.com|monograph|anakinra}} | Drugs.com = {{drugs.com|monograph|anakinra}}
| MedlinePlus = a602001 | MedlinePlus = a602001
| DailyMedID = Anakinra
| pregnancy_category = B (in some countries : contraindicated)
| pregnancy_AU = B1
| legal_status = Rx only, not a controlled substance
| pregnancy_AU_comment =
| routes_of_administration = s.c. injection only
| pregnancy_category=
| routes_of_administration = ]
| class =
| ATC_prefix = L04
| ATC_suffix = AC03
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref name="Kineret SmPC" />
| legal_US = Rx-only
| legal_US_comment = <ref name="Kineret FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Kineret EPAR">{{cite web | title=Kineret EPAR | website=] | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kineret | access-date=20 July 2021}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=COVID-19 medicines | website=European Medicines Agency (EMA) | date=14 October 2024 | url=https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/coronavirus-disease-covid-19/covid-19-medicines | access-date=14 October 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = 95% | bioavailability = 95%
| protein_bound = | protein_bound =
| metabolism = predominantly renal | metabolism = predominantly kidney
| metabolites =
| onset =
| elimination_half-life = 4-6 hrs | elimination_half-life = 4-6 hrs
| duration_of_action =
| excretion =


<!--Identifiers--> <!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| ChemSpiderID = NA
| CAS_number = 143090-92-0 | CAS_number = 143090-92-0
| ATC_prefix = L04 | PubChem =
| IUPHAR_ligand =
| ATC_suffix = AC03
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ATC_supplemental =
| PubChem =
| DrugBank = DB00026 | DrugBank = DB00026
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9013DUQ28K | UNII = 9013DUQ28K
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02934 | KEGG = D02934
| ChEBI_Ref =
| ChEMBL = <!-- blanked - oldvalue: 1201570 -->
| C=759 | H=1186 | N=208 | O=232 | S=10 | ChEBI =
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| molecular_weight = 17,257.6 g/mol
| ChEMBL = 1201570
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =

<!-- Chemical and physical data -->
| IUPAC_name = Recombinant human Interleukin-1 receptor antagonist protein; syn. N2-l-methionyl-interleukin 1 receptor antagonist (human isoform x reduced)
| C=759 | H=1186 | N=208 | O=232 | S=10
}} }}
'''Anakinra''' (brand name '''Kineret''') is a ] used to treat ].<ref name="pmid16396977">{{cite journal |author=Fleischmann RM, Tesser J, Schiff MH, ''et al.'' |title=Safety of extended treatment with anakinra in patients with rheumatoid arthritis |journal=Annals of the rheumatic diseases |volume=65 |issue=8 |pages=1006–12 |year=2006 |month=August |pmid=16396977 |doi=10.1136/ard.2005.048371 |url=http://ard.bmj.com/cgi/pmidlookup?view=long&pmid=16396977 |pmc=1798263}}</ref>


'''Anakinra''', sold under the brand name '''Kineret''', is a ] medication used to treat ], ]s, ], and ].<ref name="Kineret EPAR" /> It is a slightly modified ] version of the human ] ].<ref name="Kineret EPAR" /> It is marketed by ].<ref name="Kineret SmPC">{{cite web | title=Kineret 100 mg solution for injection in a pre-filled syringe - Summary of Product Characteristics (SmPC) |url=https://www.medicines.org.uk/emc/product/559|publisher=UK Electronic Medicines Compendium|access-date=2 March 2022 }}</ref> Anakinra is administered by ].<ref name="Kineret FDA label"/>
==Mechanism==
Anakinra is an ] (IL-1) ].<ref name="pmid17352828">{{cite journal |author=So A, De Smedt T, Revaz S, Tschopp J |title=A pilot study of IL-1 inhibition by anakinra in acute gout |journal=Arthritis research & therapy |volume=9 |issue=2 |pages=R28 |year=2007 |pmid=17352828 |pmc=1906806 |doi=10.1186/ar2143 |url=http://arthritis-research.com/content/9/2/R28}}</ref> Anakinra blocks the biologic activity of naturally occurring IL-1, including ] and cartilage degradation associated with ], by competitively inhibiting the binding of IL-1 to the Interleukin-1 type ], which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various ] responses, including ] and immunologic reactions. IL-1 additionally stimulates ] and induces tissue damage like cartilage degradation as a result of loss of ]. In patients with rheumatoid arthritis the natural IL-1 receptor antagonist is not found in effective concentrations in ] and ] to counteract the elevated IL-1 concentrations in these patients.


==Medical uses==
Anakinra is not considered a ']' (DMARD) but rather a 'Biological Response Modifier' (BRM) because its able to selectively target the pathologic element of the disease.
It is used as a second line treatment to manage symptoms of rheumatoid arthritis after treatment with a ] (DMARD) has failed.<ref name="Kineret SmPC"/><ref name="Kineret FDA label"/> It can be used in combination with some DMARDs.<ref name="Kineret SmPC"/><ref name="Kineret FDA label">{{cite web | title=Kineret- anakinra injection, solution | website=DailyMed | date=30 December 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d9d74915-6606-4570-9c52-c4001d3177de | access-date=2 March 2022}}</ref><ref name=Cochrane2016>{{cite journal | vauthors = Singh JA, Hossain A, Tanjong Ghogomu E, Kotb A, Christensen R, Mudano AS, Maxwell LJ, Shah NP, Tugwell P, Wells GA | title = 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 | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 5 | pages = CD012183 | date = May 2016 | pmid = 27175934 | pmc = 7068903 | doi = 10.1002/14651858.CD012183 }}</ref>


It is administered subcutaneously to patients diagnosed with a ], including ].<ref name="Kineret SmPC"/><ref name="Kineret FDA label"/>
==Basic chemical, pharmacological, and marketing data==
The anakinra molecule is a recombinant, non-glycosylated version of human IL-1RA (RA for receptor antagonist)prepared from cultures of genetically modified '']'' using recombinant DNA technology. It consists of 153 amino acids and has a molecular weight of 17,257.6 g/mol (approx. 17.3 kilodaltons) and differs from native human IL-1RA in that it has the addition of a single methionine residue on its amino terminus.


It is used to treat ] (off label in the US).<ref name=Gusdorf2017>{{cite journal | vauthors = Gusdorf L, Lipsker D | title = Schnitzler Syndrome: a Review | journal = Current Rheumatology Reports | volume = 19 | issue = 8 | pages = 46 | date = August 2017 | pmid = 28718061 | doi = 10.1007/s11926-017-0673-5 | s2cid = 13780498 }}</ref> Its response rate is such that it has been suggested that "Treatment failures should lead to reconsider the diagnosis."<ref>{{cite journal | vauthors = 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 | title = Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: a French multicenter study | journal = Autoimmunity Reviews | volume = 13 | issue = 10 | pages = 1035–1041 | date = October 2014 | pmid = 25220180 | doi = 10.1016/j.autrev.2014.08.031 | url = https://hal-univ-rennes1.archives-ouvertes.fr/hal-01072523/file/1-s2.0-S156899721400175X-main.pdf }}</ref>
Anakinra had an absolute bioavailability of 95% for healthy adults (n = 11) after a 70&nbsp;mg subcutaneous bolus injection. Peak plasma concentrations of anakinra generally occurred 3 to 7 hours after s.c. administration of clinically relevant doses (1 to 2&nbsp;mg/kg: n = 18) for patients with rheumatoid arthritis. The terminal half-life ranged from 4 to 6 hours. After daily s.c. dosing for up to 24 weeks, no unexpected accumulations of anakinra were observed in the plasma samples of rheumatoid arthritis patients.


], it is used to treat ] (SJIA), ], ] (CPPD), ], ], ], and other ].<ref>{{cite web|title=Anakinra (Kineret)|url=https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Anakinra-Kineret|access-date=2021-11-22|website=American College of Rheumatology.}}</ref>
This drug is sold under the ] "Kineret" and is produced by the pharmaceutical company ]. Since 15 December 2008 ] AB is the global Market Authorisation Holder for Kineret on the indication adult rheumatoid arthritis. It is delivered as injection concentrate containing 100&nbsp;mg each single dose.


In December 2021, the ] authorized the use of anakinra "to treat ] 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."<ref name="Kineret EPAR" /><ref>{{cite web | title=EMA recommends approval for use of Kineret in adults with COVID-19 | website=European Medicines Agency | date=16 December 2021 | url=https://www.ema.europa.eu/en/news/ema-recommends-approval-use-kineret-adults-covid-19 | access-date=2 March 2022}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name="aripaka">{{cite news | vauthors = Aripaka P, Karimi A |title=EU regulator builds Omicron defences with approvals of GSK-Vir, Sobi drugs |url=https://www.reuters.com/business/healthcare-pharmaceuticals/eu-regulator-okays-covid-19-treatments-gsk-vir-sobi-2021-12-16/ |access-date=17 December 2021 |publisher=Reuters |date=16 December 2021 }}</ref> In November 2022, the United States ] approved its use under an ] "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)."<ref>{{cite news|title=Sobi's Kineret granted FDA Emergency Use Authorisation for COVID-19 related pneumonia|url= https://www.pmlive.com/pharma_news/sobis_kineret_granted_fda_emergency_use_authorisation_for_covid-19_related_pneumonia_1480673|work=PMNews|date=November 2022}}</ref><ref>{{cite web|title=FDA roundup|website=] |date=November 15, 2022|url=https://www.fda.gov/news-events/press-announcements/fda-roundup-november-15-2022}}</ref>
==Indications==
Anakinra is indicated for the management of signs and symptoms of rheumatoid arthritis and to inhibit the progression of structural damage associated with the disease in adults with moderately to severely active disease who have had an absence of clinical improvement of symptoms or inadequate response in therapy with one or more disease-modifying anti-rheumatic drugs (DMARDs). It is used as monotherapeutic agent or in combination with DMARDs. Anakinra should not be used in combination with anti-TNF agents such as ] (Enbrel), ] (Remicade) or ] (Humira).


== Safety ==
Anakinra showed moderate but statistically significant therapeutic efficacy; in most studies ] was administered concomitantly. In the methotrexate plus anakinra group 38% of 250 patients reached an improvement/relief of symptoms of at least 20% within 24 weeks. In the control group of 251 patients under methotrexate treatment alone response was seen in 22% only. The clinical response was measured according to ACR-criteria (20, 50, and 70).
It was not tested in pregnant women, but appeared to be safe in animal studies.<ref name="Kineret FDA label"/>


It should not be used in people who have active infections{{Clarify|date=February 2023}} or latent tuberculosis, or who are taking ]s.<ref name="Kineret FDA label"/>
There are no direct studies comparing anakinra with TNF-α inhibitors, but indirect data suggests that anakinra may be inferior to TNF-α inhibitors. In a study with infliximab plus methotrexate 50% of all patients had significant remission (according to at least ACR 20 criteria) after a 30-week treatment period.


==Adverse reactions==
==Contraindications and precautions==
More than ten percent of people taking Anakinra have ]s, headaches, and have increased cholesterol levels.<ref name="Kineret SmPC"/> Recipients have eight percent more patients decrease ] counts, two percent more patients decrease ] counts, one percent more patients get severe infections (4.5% for patients with asthma compared to 0% placebo patients with asthma).<ref name="Kineret SmPC"/> 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.<ref name="Kineret SmPC"/><ref name=Cochrane2016/>
* ] to anakinra, other E. coli derived proteins, or to any other ingredient (absolute contraindication).
* Preexisting malignant diseases (e.g., solid ]s, ]): absolutely contraindicated (anakinra may be a human carcinogen and the suppression of immune function may worsen already existing malignancies).
* Patients with ] due to any reason : absolutely contraindicated. Neutrophil counts should be obtained before initiating therapy and regularly thereafter (see recommended laboratory tests).
* Severely impaired ] (creatinine clearance less than 30 ml/minute): absolutely contraindicated.
* Preexisting active ] (disease may be worsened – see side-effects).
* Concomitant application of live-virus vaccines (see Interactions).
* ]: it is unknown if anakinra is distributed into human milk. Nursing mothers should either discontinue the drug or breast-feeding, taking into account the importance of the drug to the mother.
* Pediatric patients: no well controlled human data exists in patients under age 18. Therefore, therapy is contraindicated in those patients.


==Chemistry==
Precautions:
Anakinra differs from the sequence of ] by one ] ] added to its ]; it also differs from the human protein in that it is not ], as it is ] in '']''.<ref name="Kineret FDA label"/>


==History==
* Geriatric patients (over 65 yrs of age): risk of infections is increased.
It was approved for medical use in the US in 2001,<ref name="Kineret FDA label"/> and in the European Union in 2002.<ref name="Kineret SmPC"/><ref name="Kineret EPAR" />
* ]: increased risk of severe infections.
* Women of childbearing potential should use effective ] methods.
* Pregnancy: animal studies showed no adverse effects. Human data is not available. The drug should be applied to pregnant women only if clearly indicated.
* Mild to moderately impaired renal function: caution.


In 2018, ] 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 ] and in cases where the first-line treatment is not effective for Familial Mediterranean fever, ] also known as ], and ] (TRAPS),<ref name="nhse-schs">{{cite book | publisher = National Health Service (NHS) | location = England |title=Clinical Commissioning Policy: Anakinra to treat periodic fevers and autoinflammatory disorders (all ages) |date=29 June 2018 |url=https://www.england.nhs.uk/wp-content/uploads/2018/07/1713-anakinra-for-periodic-fever.pdf |access-date=9 July 2018}}</ref> 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".<ref name="nhse-aosd">{{cite book | publisher = National Health Service (NHS) | location = England |title=Clinical Commissioning Policy: Anakinra/tocilizumab for the treatment of Adult-Onset Still's Disease refractory to second-line therapy (adults) |date=29 June 2018 |url=https://www.england.nhs.uk/wp-content/uploads/2018/07/1609-anakinra-and-tocilizumab-for-aosd.pdf |access-date=13 July 2018 |archive-date=13 July 2018 |archive-url=https://web.archive.org/web/20180713204934/https://www.england.nhs.uk/wp-content/uploads/2018/07/1609-anakinra-and-tocilizumab-for-aosd.pdf |url-status=dead }}</ref>
==Side-effects==
* ] : Frequently, nausea (8%), diarrhea (7%), unspecific abdominal pain (5%).
* ] : Rare cases of allergic reactions including severe ] have been noticed. If necessary, the usual symptomatic therapy with ], ], antihistaminics and i.v. fluid correction should be initiated as soon as possible. Rare cases of allergic skin ] have also been seen.
* ] : Frequently, infections of upper respiratory tract (13%), ] (7%), ] (6%), Infrequently, ] and ].
* ] : Frequently ], infrequently skin ], Lupus-erythematosis-like syndrome, ], and isolated cases of melanoma (see malignancies).
* ] : Frequently, infections (40%, severe in 2%). Infrequently, production of ] with neutralizing activity.
* Blood and blood forming organs : Frequently, decrease in neutrophil counts (8% under anakinra, placebo 2%), infrequent significant neutropenia (0.4% under anakinra), moderate ], moderate ], and malignant ]s (0.12 cases/patient year) (see malignancies).
* Musculosceletal system : Infrequent are arthritic symptoms, arthritic symptoms associated with inflammation, bony infections.
* Pain, inflammation, and erythema at injection sites : Very frequently (70% of patients), usually during first 4 weeks of therapy, reversible within 1 to 2 weeks. These reactions are reasons why many patients discontinue therapy.


In December 2020, Anakinra was approved by the US ] for the treatment of ] (DIRA), a rare autoinflammatory disease of infancy.<ref name="dira">{{cite news | vauthors = Kaufman MB |title=FDA Approves New Rituximab Biosimilar & Anakinra to Treat a Rare Disease |url=https://www.the-rheumatologist.org/article/fda-approves-new-rituximab-biosimilar-anakinra-to-treat-a-rare-disease/ |access-date=4 February 2021 |work=The Rheumatologist |date=2 February 2021}}</ref> In 2021, it was announced that the ] had approved the use of Anakinra for the treatment of ].<ref name="pharmaletter2021">{{cite web |title=Kineret approved in Russia for the treatment of CAPS |url=https://www.thepharmaletter.com/article/kineret-approved-in-russia-for-the-treatment-of-caps |website=The Pharma Letter |access-date=18 February 2021 |date=17 February 2021}}</ref>
==Recommended Laboratory Tests==
In patients receiving anakinra a decrease in neutrophil counts may be found. In the placebo-controlled studies 8% of patients receiving anakinra had decreases in neutrophil counts of at least 1 ] (WHO) toxicity grade compared with 2% in the placebo control group. anakinra-treated patients experienced defined neutropenia (ANC < 1 x 109/L) in 0.4%.


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 ].<ref name="nhse-hlh">{{cite book | publisher = National Health Service (NHS) | location = England |title=Clinical Commissioning Policy: Anakinra for Haemophagocytic Lymphohistiocytosis (HLH) for adults and children in all ages |date=October 2021 |url=https://www.england.nhs.uk/wp-content/uploads/2021/10/1924-Clinical-commissioning-policy-anakinra-for-haemophagocytic-lymphohistiocytosis-1.pdf |access-date=14 October 2021 |archive-date=13 October 2021 |archive-url=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 |url-status=dead }}</ref>
'''Neutrophil counts should be assessed prior to initiating anakinra treatment, and while receiving anakinra, monthly for 3 months, and thereafter quarterly for a period up to 1 year.'''


== Society and culture ==
==Malignancies==
=== Legal status ===
Among 5,300 rheumatoid arthritis patients treated with anakinra in clinical trials for a mean of 15 months (approximately 6,400 patient years of treatment), 8 cases of lymphomas were observed resulting in a rate of 0.12 cases/100 patient years. This is 3.6 fold higher than the rate of lymphomas expected in the general population. However, the 'natural' incidence of lymphomas in patients with rheumatoid arthritis is considerably increased and may even be higher in patients with high disease activity.
{| class="wikitable"
|+Approvals
!
! colspan="9" |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 ==
Additionally, 37 solid tumors of different origination have been found. Of these, the number of 3 melanomas reported in study 4 is significant (1 case expected), but the clear association to anakinra therapy remains unclear.
Anakinra effectively treated meningitis caused by a rare genetic mutation in the gene ] in a 67-year-old man enrolled in the ].<ref>{{cite news|url=https://www.nytimes.com/2019/01/07/health/patients-medical-mysteries.html|title=When the Illness Is a Mystery, Patients Turn to These Detectives| vauthors = Kolata G |date=2019-01-07|work=The New York Times|access-date=2019-01-09}}</ref> Researchers at ] announced in 2019 that anakinra given to pregnant mice with ] had reduced fetal deaths and birth defects.<ref name="johns">{{cite news |title=Rheumatoid Arthritis Drug Diminishes Zika Birth Defects in Mice |url=https://www.hopkinsmedicine.org/news/newsroom/news-releases/rheumatoid-arthritis-drug-diminishes-zika-birth-defects-in-mice |access-date=5 September 2019 |work=Newsroom |publisher=Johns Hopkins Medicine |date=6 May 2019}}</ref> In November 2019, researchers at the ] reported that Anakinra might have a use in preventing breast cancer from spreading to the bones.<ref name="manchester-2019">{{cite news |title=Arthritis drugs could be repurposed to help prevent breast cancer spreading to the bone, study suggests |url=https://www.manchester.ac.uk/discover/news/arthritis-drugs-could-be-repurposed-to-help-prevent-breast-cancer-spreading-to-the-bone-study-suggests/ |access-date=21 November 2019 |work=Press release |publisher=University of Manchester |date=20 November 2019}}</ref><ref name="eyre">{{cite journal | vauthors = 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 | title = Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling | journal = Nature Communications | volume = 10 | issue = 1 | pages = 5016 | date = November 2019 | pmid = 31676788 | pmc = 6825219 | doi = 10.1038/s41467-019-12807-0 | bibcode = 2019NatCo..10.5016E }}</ref>


In 2021, it was reported that Anakinra appeared to reduce the ] experienced by patients undergoing ] with ], saying that "repurposing anakinra may be an effective co-treatment strategy to prevent vincristine-induced peripheral neuropathy".<ref name="starabova">{{cite journal | vauthors = 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 | title = Vincristine-induced peripheral neuropathy is driven by canonical NLRP3 activation and IL-1β release | journal = The Journal of Experimental Medicine | volume = 218 | issue = 5 | pages = e20201452 | date = May 2021 | pmid = 33656514 | pmc = 7933984 | doi = 10.1084/jem.20201452 }}</ref><ref name="queensland">{{cite web |title=Chemotherapy with fewer side effects may be on the way |url=https://www.uq.edu.au/news/article/2021/02/chemotherapy-fewer-side-effects-may-be-way-0 |publisher=University of Queensland |access-date=15 March 2021 |date=15 March 2021}}</ref>
The Cochrane Collaboration (www.cochrane.org) is an independent body which produces systematic literature reviews to a high academic standard. The Cochrane review entitled, ‘Anakinra for rheumatoid arthritis’ (Mertens and Singh, 2009; http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD005121/pdf_standard_fs.html) evaluates the clinical effectiveness and safety of anakinra in adult patients with rheumatoid arthritis, using data from 2876 patients, from five trials which constituted in total 781 randomized to placebo and 2065 to anakinra. The authors conclude, “There were no statistically significant differences noted in most safety outcomes with treatment with anakinra versus placebo - including number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). Injection site reactions were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%) of patients treated with anakinra versus placebo, respectively”. These injection site reactions last for no more than four months and are not serious. Each of the trials reviewed measured prevalence of malignancies and found no evidence that these are increased amongst patients taking anakinra.


A review published in 2022 found that "Anakinra appears to show efficacy for numerous ] conditions, with the strongest evidence for ], ], ], and ]." 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."<ref>{{cite journal | vauthors = Tegtmeyer K, Atassi G, Zhao J, Maloney NJ, Lio PA | title = Off-Label studies on anakinra in dermatology: a review | journal = The Journal of Dermatological Treatment | volume = 33 | issue = 1 | pages = 73–86 | date = February 2022 | pmid = 32279586 | doi = 10.1080/09546634.2020.1755417 | s2cid = 215749189 }}</ref>
==Interactions==
* TNF-Blocking Agents:
An increased incidence of serious infections and an increased risk of neutropenia have been seen when anakinra and etanercept were used concomitantly in patients with rheumatoid arthritis. Similar interactions can be anticipated for the combination therapy of anakinra together with other agents blocking TNF (alpha) (e.g., adalimumab, infliximab). Therefore, combined drug therapy with anakinra and any TNF-blocking agent is not recommended and should be avoided. Moreover, in a 24-week clinical study a regime with anakinra and etanercept did not provide any additional benefit to the patients.


In 2023, researchers at ] explored the effect of Anakinra on the ageing of ]s 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".<ref>{{cite news | vauthors = Caler L |title=This Arthritis Drug Could Rejuvenate Blood In The Elderly, Delay Aging |url=https://www.medicaldaily.com/arthritis-drug-could-rejuvenate-blood-elderly-delay-aging-467939 |access-date=6 February 2023 |work=Medical Daily |date=1 February 2023 |language=en}}</ref><ref name="mitchell">{{cite journal | vauthors = 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 | title = Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing | journal = Nature Cell Biology | volume = 25 | issue = 1 | pages = 30–41 | date = January 2023 | pmid = 36650381 | doi = 10.1038/s41556-022-01053-0 | pmc = 7614279 }}</ref><ref>{{cite news|url=https://newatlas.com/medical/arthritis-drug-young-blood-reverses-aging-mice/|title=Arthritis drug mimics "young blood" transfusions to reverse aging in mice| vauthors = Irving M |date=6 February 2023 |work=New Atlas|access-date=6 February 2023}}</ref>
* Methotrexate:
Methotrexate has been coadministered with anakinra in quite extended clinical studies. Neither specific drug interactions nor increased toxicity of anakinra and/or methotrexate have been noticed. In animal models (rats) studying the effects of both drugs when coadminstered, no effects on clearing of both drugs form plasma or on the respective toxicologic properties have been seen. Therefore, the concomitant use of both disease modifiers in patients with rheumatoid arthritis can be regarded as safe.


A 2023 preliminary study on the use of Anakinra in the treatment of ] concluded that "there is justification for a larger study" and that "Anakinra may be a particularly impactful option for women desiring fertility."<ref name="Sullender_2023">{{cite journal | vauthors = Sullender R, Agarwal R, Jacobs M, Valentine H, Foster L, Agarwal SK |title=10217 IL-1 Antagonist Anakinra for the Treatment of Endometriosis: A Placebo Controlled, Randomized Pilot Study |journal=] |date=November 2023 |volume=30 |issue=11 |pages=S107 |doi=10.1016/j.jmig.2023.08.342|s2cid=264540594 }}</ref>
* Vaccines:
Live-virus vaccines should not be given to patients during anakinra treatment. Information is not available, if anakinra would affect the rate of secondary transmission of vaccine virus (e.g., measles or poliomyelitis viruses) following administration of a live virus vaccine or regarding any other effect of vaccination on patients receiving the drug. Due to the fact that anakinra decreases the immune response to antigens in general, vaccine efficacy may be reduced in patients receiving anakinra.


==Dosage regimen== === COVID-19 ===
{{anchor|COVID-19 research}}
The usual dosage is 100&nbsp;mg subcutaneosly (s.c.) once a day. Dose reduction to 100&nbsp;mg s.c. every other day should be considered in patients with severe renal impairment, if these are treated in exceptional cases (see contraindications and precautions). No additional benefits of doses exceeding 100&nbsp;mg daily have been seen.


Anakinra is undergoing multiple clinical trials to treat ] patients, by targeting mechanisms in patients with hyperinflammation.<ref name="The Lancet">{{cite news |title=Anakinra in COVID-19: important considerations for clinical trials |url=https://www.researchgate.net/publication/341554901 |access-date=5 January 2021 |work=Press release |date=May 2020}}</ref> In 2021 a review and ] 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."<ref name="barkas">{{cite journal | vauthors = Barkas F, Filippas-Ntekouan S, Kosmidou M, Liberopoulos E, Liontos A, Milionis H | title = Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis | journal = Rheumatology | volume = 60 | issue = 12 | pages = 5527–5537 | date = December 2021 | pmid = 33999135 | pmc = 8194671 | doi = 10.1093/rheumatology/keab447 }}</ref>
==Duration of treatment==
In the pre-clinical and clinical studies the usual duration of therapy was 24 weeks. It is possible to extend therapy to 48 weeks in patients with satisfying remission after 24 weeks to maintain clinically evident improvements. Under continued therapy anakinra has been shown to slow progression of disease over a period of at least 12 month evidenced by X-ray studies or other clinical examinations. Some experience with 48 to 60 weeks (15 months) treatment duration has already been gained and no evidence has been seen regarding additional toxicity.


{{As of|2021|July}}, the ] (EMA) is evaluating an application to extend the use of anakinra to include treatment of ] in adults with pneumonia who are at risk of developing severe respiratory failure (inability of the lungs to work properly).<ref>{{cite press release | title=EMA starts evaluating the use of Kineret in adult COVID-19 patients at increased risk severe respiratory failure | website=] (EMA) | date=16 July 2021 | url=https://www.ema.europa.eu/en/news/ema-starts-evaluating-use-kineret-adult-covid-19-patients-increased-risk-severe-respiratory-failure | access-date=20 July 2021}}</ref> According to study results published in September 2021 in '']'', hospitalized COVID-19 patients at increased risk for ] showed significant improvement after treatment with Anakinra.<ref>{{cite journal | vauthors = 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 | title = Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial | journal = Nature Medicine | volume = 27 | issue = 10 | pages = 1752–1760 | date = October 2021 | pmid = 34480127 | pmc = 8516650 | doi = 10.1038/s41591-021-01499-z | doi-access = free }}</ref><ref>{{cite web|title=Anakinra improved survival in hospitalized COVID-19 patients|url=https://www.mdedge.com/rheumatology/article/245801/coronavirus-updates/anakinra-improved-survival-hospitalized-covid-19|access-date=2021-09-09|website=www.mdedge.com}}</ref>
==Possible future indications==
Due to the specific mechanism of action of anakinra, a possible efficiency may be anticipated in patients with inflammatory joint diseases such as ], and ]. Possibly, anakinra may even benefit patients with destructive ] in inflammatory phases. Anakinra may also be effective in pediatric patients with ] (JRA). '''Clinical studies have not been initiated so far regarding these diseases. Currently, the use of anakinra in these patients is therefore not recommended.'''


== References ==
On April 12, 2007 an article in the ] discussed the possibility of using anakinra for treatment of ].<ref>{{cite web | url = http://uk.reuters.com/article/2007/04/12/health-type-2-diabetes-dc-idUKCOL24490420070412 | title = New type of drug helpful in type 2 diabetes | accessdate = 2011-04-28 | date = 2007-04-12 | publisher = ]}}</ref> A few studies have looked at the effectiveness of anakinra in some familial ]s.

On May 2, 2008 an article in the review ] discussed the possibility of using anakinra for treatment of ].
"Since Anakinra (IL-1ra) is efficiently used in the clinical treatment of autoinflammatory
syndromes as well as gout patients, the present study suggests a potential use of
Anakinra in order to slow down progression of asbestosis, silicosis and possibly other
inflammatory lung diseases."
<ref>{{cite journal | title = Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica | journal = Science | date = 2008-05-02 | first = Catherine | last = Dostert | coauthors = Virginie Pétrilli, Robin Van Bruggen, Chad Steele, Brooke T. Mossman, Jürg Tschopp | volume = 320 | issue = 5876 | pages = 674–7| id = | url = http://www.sciencemag.org/content/320/5876/674.short | accessdate = 2011-04-28 | doi=10.1126/science.1156995 | pmid = 18403674 | pmc = 2396588}}</ref>
There is anecdotal evidence suggesting that IL-1 inhibitors may indeed be effective in gouty arthritis,and this approach is currently under study.<ref>{{cite journal|author=Arthur Kavanaugh |title=Gout:Treatment Reaction to Allopurinol- - What Next?|journal=Medscape Rheumatology | url = http://www.medscape.com/viewarticle/563931}}</ref>

In 2008, an article in the European Journal of Pediatrics discussed treatment of ]-resistant ] with anakinra.<ref>{{cite journal | title = The efficacy of anakinra in an adolescent with colchicine-resistant familial Mediterranean fever | journal = European Journal of Pediatrics | date = 2008-06-01 | first = Lorenzo | last = Calligaris | coauthors = Federico Marchetti, Alberto Tommasini, Alessandro Ventura | volume = 167 | issue = 6 | pages = 695–6 | accessdate = 2011-04-28 | pmid=17588171 | doi=10.1007/s00431-007-0547-3 | pmc = 2292480}}</ref>

==References==
{{Reflist}} {{Reflist}}


==External links==
*
* http://www.rheuma-online.de/medikamente/anakinra-kineret/anakinra-zb-kineret/tumorrisiko.html (on the risk of cancerogenity (in German))
* http://www.rheuma-online.de/medikamente/anakinra-kineret/anakinra-zb-kineret/ausblicke-moegliche-zukuenftige-anwendungen-von-anakinra-kineret.html (same site on future indications)
* http://www.rheuma-online.de/medikamente/anakinra-kineret/anakinra-zb-kineret/anakinra-kineret-in-der-kinderrheumatologie.html (same site on possible pediatric indications)
{{Immunosuppressants}} {{Immunosuppressants}}
{{Interleukin receptor modulators}}
{{Portal bar | Medicine | Viruses | COVID-19}}


] ]
]

]
]
]
]
]