Canakinumab (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

), sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis (SJIA) and active Still's disease, including

adult-onset Still's disease 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 diagnos ...

(AOSD). It is a human

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha. Common side effects include infections (colds and upper respiratory tract infections), abdominal pain and injection-site reactions.

Medical uses

Canakinumab was approved for the treatment of

cryopyrin-associated periodic syndrome Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by Interleukin 1 beta, interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervo ...

s (CAPS) by the U.S.

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 ...

(FDA) in June 2009 and by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) in October 2009. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. CAPS is a spectrum of autoinflammatory syndromes including Familial Cold Autoinflammatory Syndrome (FCAS), Muckle–Wells syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID). In September 2016, the FDA approved the use of canakinumab for three additional rare and serious auto-inflammatory diseases: tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/

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 ...

(MKD), and

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 su ...

(FMF). In June 2020, canakinumab was approved in the United States for the indication to treat active Still's disease, including

(AOSD). In the European Union, canakinumab is indicated for autoinflammatory periodic fever syndromes,

s (CAPS), tumour necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/

(MKD),

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 su ...

(FMF), Still's disease, and

gouty arthritis 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 intensit ...

Adverse effects

The FDA prescribing information for canakinumab (Ilaris) includes a warning for potential increased risk of serious infections due to IL-1 blockade. Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in people with rheumatic conditions, in particular Still's disease, and should be aggressively treated. Treatment with immunosuppressants may increase the risk of malignancies. People are advised not to receive live vaccinations during treatment.

History

Canakinumab was being developed by

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

for the treatment of

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 involv ...

, but this trial was completed in October 2009. Canakinumab is also in phase I

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s as a possible treatment for

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

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 intensit ...

, and

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

(the CANTOS trial). It is also in trials for

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

. In gout, it may result in better outcomes than a low dose of a steroid, but costs five thousand times more. One 150 mg subcutaneous injection, usually needed every two weeks, costs over $16,700. On 27 August 2017, the results of the CANTOS trial were announced at the

European Society of Cardiology The European Society of Cardiology (ESC) is an independent non-profit, non-governmental professional association that works to advance the prevention, diagnosis and management of diseases of the heart and blood vessels, and improve scientific un ...

and published in ''

The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...

'' and ''

The New England Journal of Medicine ''The New England Journal of Medicine'' (''NEJM'') is a weekly medical journal published by the Massachusetts Medical Society. It is among the most prestigious peer-reviewed medical journals as well as the oldest continuously published one. His ...

''. Those treated in CANTOS had a 15% reduction in deaths from heart attacks, stroke and cardiovascular disease combined. However, there were serious side-effects and no statistically significant overall survival benefit. Although the CANTOS study says, "Overall, canakinumab was tolerated well with essentially identical discontinuation rates compared to placebo. Mild neutropenia and thrombocytopenia were slightly more common in those treated with canakinumab. Rates of death due to infection or sepsis were low but more likely in the canakinumab group compared to placebo (incidence rate 0.31 vs. 0.18 per 100 person-years, ''P'' = 0.02). In terms of the types of infections that occurred during follow up, only pseudomembranous colitis was more common in the canakinumab group; no evidence of opportunistic infection was observed, data emphasizing that canakinumab is not a clinically immunosuppressive intervention. Further demonstrating this issue, random allocation to canakinumab as compared to placebo in CANTOS resulted in large and highly significant dose-dependent reductions in cancer fatality, incident lung cancer, and fatal lung cancer." Nonetheless, David Goff, director of the division of cardiovascular sciences at the

National Heart, Lung and Blood Institute The National Heart, Lung, and Blood Institute (NHLBI) is the third largest Institute of the National Institutes of Health, located in Bethesda, Maryland, United States. It is tasked with allocating about $3.6 billion in FY 2020 in tax revenue to ...

feels the "public health impact potential is really substantial," and estimates that in the United States 3 million people might benefit from canakinumab. Further analysis on data from the CANTOS trial also showed a significant reduction in lung cancer incidence and mortality in the canakinumab treated group compared to placebo.

References

External links

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