Clinical data | |
---|---|
Trade names | Kineret |
AHFS/Drugs.com | Monograph |
MedlinePlus | a602001 |
License data | |
Pregnancy category |
|
Routes of administration | Subcutaneous |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 95% |
Metabolism | predominantly kidney |
Elimination half-life | 4-6 hrs |
Identifiers | |
| |
CAS Number | |
DrugBank | |
ChemSpider |
|
UNII | |
KEGG | |
ChEMBL | |
Chemical and physical data | |
Formula | C759H1186N208O232S10 |
Molar mass | 17257.66 g·mol−1 |
(what is this?) (verify) |
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. [3] It is a slightly modified recombinant version of the human interleukin 1 receptor antagonist protein. [3] It is marketed by Swedish Orphan Biovitrum. [1] Anakinra is administered 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] [4]
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). [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 treat systemic juvenile idiopathic arthritis (SJIA), gout, calcium pyrophosphate deposition (CPPD), Behçet's disease, ankylosing spondylitis, uveitis, and other auto-inflammatory syndromes. [7]
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." [3] [8] [9] 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)." [10] [11]
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 taking TNF inhibitors. [2]
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] [4]
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]
It was approved for medical use in the US in 2001, [2] and in the European Union in 2002. [1] [3]
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), [12] 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". [13]
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. [14] 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. [15]
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. [16]
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 |
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. [17] Researchers at Johns Hopkins University announced in 2019 that anakinra given to pregnant mice with Zika virus had reduced fetal deaths and birth defects. [18] 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. [19] [20]
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". [21] [22]
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." [23]
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". [24] [25] [26]
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." [27]
Anakinra is undergoing multiple clinical trials to treat COVID-19 patients, by targeting mechanisms in patients with hyperinflammation. [28] 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." [29]
As of July 2021 [update] , 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). [30] 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. [31] [32]
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.
Sjögren syndrome or Sjögren's syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands, and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system.
Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.
Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated disease-modifying drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to nonsteroidal anti-inflammatory drugs and steroids.
Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.
Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. It is taken by mouth, often in the form of hydroxychloroquine sulfate.
Leflunomide, sold under the brand name Arava among others, is an immunosuppressive disease-modifying antirheumatic drug (DMARD), used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.
Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID‑19. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.
Canakinumab, sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis, active Still's disease, including adult-onset Still's disease, gout flares. It is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.
Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagnosis of exclusion. Levels of the iron-binding protein ferritin may be extremely elevated with this disorder. AOSD may present in a similar manner to other inflammatory diseases and to autoimmune diseases, which must be ruled out before making the diagnosis.
Schnitzler syndrome or Schnitzler's syndrome is a rare disease characterised by onset around middle age of chronic hives (urticaria) and periodic fever, bone pain and joint pain, weight loss, malaise, fatigue, swollen lymph glands and enlarged spleen and liver.
Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, the Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease that were originally thought to be distinct entities, but in fact share a single genetic mutation and pathogenic pathway, and keratoendotheliitis fugax hereditaria in which the autoinflammatory symptoms affect only the anterior segment of the eye.
A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes, thereby interfering with the JAK-STAT signaling pathway in lymphocytes.
Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.
Sarilumab, sold under the brand name Kevzara, is a human monoclonal antibody medication against the interleukin-6 receptor. Regeneron Pharmaceuticals and Sanofi developed the drug for the treatment of rheumatoid arthritis (RA), for which it received US FDA approval on 22 May 2017 and European Medicines Agency approval on 23 June 2017.
Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It is taken by mouth.
Systemic juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis (JIA) with extra-articular manifestations like fever and rash apart from arthritis. It was originally called systemic-onset juvenile rheumatoid arthritis or Still's disease.
Filgotinib, sold under the brand name Jyseleca, is a medication used for the treatment of rheumatoid arthritis (RA). It was developed by the Belgian-Dutch biotech company Galapagos NV.
An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.