Anakinra, sold under the brand name Kineret, is a

biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...

medication used to treat

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...

cryopyrin-associated periodic syndrome 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 ...

familial Mediterranean fever Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in Mediterranean fever gene, which encodes a 781–amino acid protein called pyrin. While all ethnic groups are sus ...

, and Still's disease. It is a recombinant and slightly modified version of the human

interleukin 1 receptor antagonist The interleukin-1 receptor antagonist protein (IL-1RN) is a protein that in humans is encoded by the ''IL1RN'' gene. IL-1RN was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. IL-1RN is a ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

. It is marketed by Swedish Orphan Biovitrum. 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 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 nonsteroida ...

(DMARD) has failed. It can be used in combination with some DMARDs. It is used to people with a

, including

neonatal-onset multisystem inflammatory disease Neonatal-onset multisystem inflammatory disease is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period. Symptoms include skin rashes, severe arthritis, and chro ...

. It is used to treat Schnitzler's syndrome (off label in the US). Its response rate is such that it has been suggested that "Treatment failures should lead to reconsider the diagnosis." Off label, it is used to treat systemic juvenile idiopathic arthritis (SJIA),

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...

, calcium pyrophosphate deposition (CPPD),

Behçet's disease Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the ey ...

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hi ...

uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...

, and other auto-inflammatory syndromes. In December 2021, the European Medicines Agency authorized the use of anakinra "to treat

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickly ...

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." In November 2022, the United States FDA approved its use under an

emergency use authorization An Emergency Use Authorization (EUA) in the United States is an authorization granted to the Food and Drug Administration (FDA) under sections of the Federal Food, Drug, and Cosmetic Act as added to and amended by various Acts of Congress, includ ...

"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)."

Safety

It was not tested in pregnant women, but appeared to be safe in animal studies. It should not be used in people who have active infections or latent tuberculosis, who have low

white blood cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

counts, or who are taking TNF inhibitors.

Adverse effects

More than ten percent of people taking Anakinra have

injection site reaction Injection site reactions are allergic reactions that result in cutaneous necrosis that may occur at sites of medication injection, typically presenting in one of two forms, (1) those associated with intravenous infusion or (2) those related to intra ...

s, headaches, and have increased cholesterol levels. Between one and ten percent of recipients have severe infections, decreased white blood cells, or decreased platelets. 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.

Chemistry

Anakinra differs from the sequence of

Interleukin 1 receptor antagonist The interleukin-1 receptor antagonist protein (IL-1RN) is a protein that in humans is encoded by the ''IL1RN'' gene. IL-1RN was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. IL-1RN is a ...

by one methionine

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

added to its N-terminus; it also differs from the human protein in that it is not glycosylated, as it is

manufactured Manufacturing is the creation or production of goods with the help of equipment, labor, machines, tools, and chemical or biological processing or formulation. It is the essence of secondary sector of the economy. The term may refer to a ran ...

in ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

''.

History

It was approved for medical use in the US in 2001, and in the European Union in 2002. 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 Mevalonate kinase deficiency (MKD) is an autosome, autosomal Dominance (genetics), recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. It is a Rare genetic disease, very rare genetic disease. It is charact ...

also known as

Mevalonate kinase deficiency Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. It is a very rare genetic disease. It is characterized by an elevated level of immunoglobulin D in th ...

, and

TNF receptor associated periodic syndrome TNF receptor associated periodic syndrome (TRAPSsubscription needed) is a periodic fever syndrome associated with mutations in a receptor for the molecule tumor necrosis factor (TNF) that is inheritable in an autosomal dominant manner. Individua ...

(TRAPS), 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". In December 2020, Anakinra was approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

for the treatment of deficiency of the interleukin-1–receptor antagonist (DIRA), a rare autoinflammatory disease of infancy. 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 Caps are flat headgear. Caps or CAPS may also refer to: Science and technology Computing * CESG Assisted Products Service, provided by the U.K. Government Communications Headquarters * Composite Application Platform Suite, by Java Caps, a Ja ...

. 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.

Society and culture

Legal status

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. Researchers at

Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hemisphere. It consi ...

announced in 2019 that anakinra given to pregnant mice with

Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active '' Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, w ...

had reduced fetal deaths and birth defects. In November 2019, researchers at the

University of Manchester , mottoeng = Knowledge, Wisdom, Humanity , established = 2004 – University of Manchester Predecessor institutions: 1956 – UMIST (as university college; university 1994) 1904 – Victoria University of Manchester 1880 – Victoria Univ ...

reported that Anakinra might have a use in preventing breast cancer from spreading to the bones. In 2021, it was reported that Anakinra appeared to reduce the

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...

experienced by patients undergoing

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

with

vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...

, saying that "repurposing anakinra may be an effective co-treatment strategy to prevent vincristine-induced peripheral neuropathy". A review published in 2022 found that "Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa,

Muckle–Wells syndrome Muckle–Wells syndrome (MWS) is a rare autosomal dominant disease which causes sensorineural deafness and recurrent hives, and can lead to amyloidosis. Individuals with MWS often have episodic fever, chills, and joint pain. As a result, MWS is ...

, and

SAPHO syndrome SAPHO syndrome includes a variety of inflammatory bone disorders that may be associated with skin changes. These diseases share some clinical, radiologic, and pathologic characteristics. An entity initially known as chronic recurrent multifocal ...

." 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."

COVID-19

Anakinara is undergoing multiple clinical trials to treat

patients, by targeting mechanisms in patients with hyperinflammation. In 2021 a review and

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

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." , the European Medicines Agency (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). According to study results published in September 2021 in ''

Nature Medicine ''Nature Medicine'' is a monthly peer-reviewed medical journal published by Nature Portfolio covering all aspects of medicine. It was established in 1995. The journal seeks to publish research papers that "demonstrate novel insight into disease ...

'', hospitalized COVID-19 patients at increased risk for

respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...

showed significant improvement after treatment with Anakinra.

References

External links

* {{Portal bar , Medicine , Viruses , COVID-19 Immunosuppressants Disease-modifying antirheumatic drugs