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Canakinumab (INN, trade name Ilaris, previously ACZ885) 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.
Canakinumab was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS) by the U.S. Food and Drug Administration (FDA) in June 2009 and by the European Medicines Agency in October 2009. 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, FDA approved the use of canakinumab on 3 additional rare and serious auto-inflammatory diseases: tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) and familial mediterranean fever (FMF).
Canakinumab was being developed by Novartis for the treatment of rheumatoid arthritis, but this trial was completed in October 2009. Canakinumab is also in phase I clinical trials as a possible treatment for chronic obstructive pulmonary disease, gout, and coronary artery disease (the CANTOS trial). It is also in trials for schizophrenia. 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; discounts are sometimes available.
On August 27, 2017, the results of the CANTOS trial were announced at the European Society of Cardiology and published in The Lancet and the New England Journal of Medicine. 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 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.
- Rondeau JM, Ramage P, Zurini M, Gram H (2015). "The molecular mode of action and species specificity of canakinumab, a human monoclonal antibody neutralizing IL-1β". MAbs. 7 (6): 1151–60. doi:10.1080/19420862.2015.1081323. PMC 4966334. PMID 26284424.CS1 maint: uses authors parameter (link)
- Dhimolea, Eugen (2010). "Canakinumab". MAbs. 2 (1): 3–13. doi:10.4161/mabs.2.1.10328. PMC 2828573. PMID 20065636.
- Lachmann, HJ; Kone-Paut I; Kuemmerle-Deschner JB; et al. (4 June 2009). "Use of canakinumab in the cryopyrin-associated periodic syndrome". N Engl J Med. 360 (23): 2416–25. doi:10.1056/NEJMoa0810787. PMID 19494217.
- "New biological therapy Ilaris approved in US to treat children and adults with CAPS, a serious life-long auto-inflammatory disease" (Press release). Novartis. 18 June 2009. Archived from the original on 22 June 2009. Retrieved 28 July 2009.
- Wan, Yuet (29 October 2009). "Canakinumab (Ilaris) and rilonacept (Arcalyst) approved in EU for treatment of cryopyrin-associated periodic syndrome". National electronic Library for Medicines. Archived from the original on 2 October 2011. Retrieved 14 April 2010.
- "FDA approves expanded indications for Ilaris for three rare diseases". FDA News Release. 23 September 2016.
- "clinicaltrials.gov, Identifier NCT00784628: Safety, Tolerability and Efficacy of ACZ885 (Canakinumab) in Patients With Active Rheumatoid Arthritis". Retrieved 21 August 2010.
- Yasothan U, Kar S (2008). "Therapies for COPD". Nat Rev Drug Discov. 7 (4): 285. doi:10.1038/nrd2533.
- "CANTOS Summary". theCANTOS.org.
- "Archived copy". Archived from the original on 4 November 2016. Retrieved 4 November 2016.CS1 maint: archived copy as title (link)
- Sivera, F; Wechalekar, MD; Andrés, M; Buchbinder, R; Carmona, L (1 September 2014). "Interleukin-1 inhibitors for acute gout". The Cochrane Database of Systematic Reviews. 9: CD009993. doi:10.1002/14651858.CD009993.pub2. PMID 25177840.
- Johnson, Carolyn (27 August 2017). "Major drug study opens up vast new opportunities in combating heart disease". The Washington Post.
- Aday, Aaron W.; Ridker, Paul M. (2018). "Antiinflammatory Therapy in Clinical Care: The CANTOS Trial and Beyond". Frontiers in Cardiovascular Medicine. 5. doi:10.3389/fcvm.2018.00062. ISSN 2297-055X.
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