Canakinumab

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Canakinumab
Canakinumab bound to IL-1b.png
Ribbon diagram of canakinumab (blue) bound to IL-1β (yellow) from PDB entry 5bvp [1]
Monoclonal antibody
Type Whole antibody
Source Human
Target IL-1β
Clinical data
Trade names Ilaris
Other namesACZ885, ACZ-885
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		Intravenous, subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C6452H9958N1722O2010S42
Molar mass 145157.20 g·mol−1
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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. [4] [5] [6] 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. [7]

Contents

Common side effects include infections (colds and upper respiratory tract infections), abdominal pain and injection-site reactions. [2] [3] [4]

Medical uses

Canakinumab was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS) by the U.S. Food and Drug Administration (FDA) in June 2009, [2] [8] and by the European Medicines Agency (EMA) in October 2009. [3] [9] 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: [10] tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), and familial mediterranean fever (FMF). [10]

In June 2020, canakinumab was approved in the United States for the indication to treat active Still's disease, including adult-onset Still's disease. [4]

In the European Union, canakinumab is indicated for autoinflammatory periodic fever syndromes, cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), familial Mediterranean fever (FMF), Still's disease, and gouty arthritis. [3]

In August 2023, the FDA expanded coverage to cover the treatment of gout flares. [6]

Adverse effects

Injection site reactions such as redness and pain are common, occurring in approximately 15.5% of cases. [11] The FDA prescribing information for canakinumab (Ilaris) includes a warning for potential increased risk of serious infections due to IL-1 blockade. [4] 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. [4] Treatment with immunosuppressants may increase the risk of malignancies. [4] People are advised not to receive live vaccinations during treatment. [4] [2]

History

Canakinumab was being developed by Novartis for the treatment of rheumatoid arthritis, but this trial was completed in October 2009. [12] Canakinumab is also in phase I clinical trials as a possible treatment for chronic obstructive pulmonary disease, [13] gout, and coronary artery disease (the CANTOS trial [14] ). It is also in trials for schizophrenia. [15] In gout, it may result in better outcomes than a low dose of a steroid, but costs five thousand times more. [16]

In August 2017, the results of the CANTOS trial were announced at the European Society of Cardiology. [17] 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." [18] 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. [17] 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. [19]

In August 2023, the FDA approved canakinumab for the symptomatic treatment of adults with gout flares in whom nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate based on three studies. [6]

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References

  1. ↑ 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): 1151–1160. doi:10.1080/19420862.2015.1081323. PMC   4966334 . PMID   26284424.
  2. 1 2 3 4 "Ilaris- canakinumab injection, powder, lyophilized, for solution Ilaris- canakinumab injection, solution". DailyMed. 14 September 2019. Retrieved 16 June 2020.
  3. 1 2 3 4 "Ilaris EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 16 June 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  4. 1 2 3 4 5 6 7 "FDA Approves First Treatment for Adult Onset Still's Disease, a Severe and Rare Disease". U.S. Food and Drug Administration (FDA) (Press release). 16 June 2020. Retrieved 16 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. ↑ Dhimolea E (2010). "Canakinumab". mAbs. 2 (1): 3–13. doi:10.4161/mabs.2.1.10328. PMC   2828573 . PMID   20065636.
  6. 1 2 3 "FDA Approves Canakinumab for Gout Flares" . Medscape. Retrieved 1 September 2023.
  7. ↑ Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, et al. (June 2009). "Use of canakinumab in the cryopyrin-associated periodic syndrome". The New England Journal of Medicine. 360 (23): 2416–2425. doi: 10.1056/NEJMoa0810787 . PMID   19494217.
  8. ↑ "Drug Approval Package: Ilaris (canakinumab) Subcutaneous Injection NDA #125319". U.S. Food and Drug Administration (FDA). 26 August 2009. Retrieved 23 February 2023.
  9. ↑ Wan Y (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.
  10. 1 2 "FDA approves expanded indications for Ilaris for three rare diseases" (Press release). U.S. Food and Drug Administration (FDA). 23 September 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  11. ↑ Kim PJ, Lansang RP, Vender R (July 2023). "A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections". Journal of Cutaneous Medicine and Surgery. 27 (4): 358–367. doi:10.1177/12034754231188444. PMC   10486173 . PMID   37533141.
  12. ↑ Clinical trial number NCT00784628 for "Safety, Tolerability and Efficacy of ACZ885 (Canakinumab) in Patients With Active Rheumatoid Arthritis" at ClinicalTrials.gov
  13. ↑ Yasothan U, Kar S (2008). "Therapies for COPD". Nat Rev Drug Discov. 7 (4): 285. doi:10.1038/nrd2533. S2CID   29625221.
  14. ↑ "CANTOS Summary". theCANTOS.org. Archived from the original on 15 October 2017. Retrieved 6 June 2017.
  15. ↑ "Canakinumab Add-On Treatment for Schizophrenia (CATS) Study". NeuRA. Archived from the original on 4 November 2016. Retrieved 4 November 2016.
  16. ↑ Sivera F, Wechalekar MD, Andrés M, Buchbinder R, Carmona L (September 2014). "Interleukin-1 inhibitors for acute gout". The Cochrane Database of Systematic Reviews. 9 (9): CD009993. doi:10.1002/14651858.CD009993.pub2. PMC   10891421 . PMID   25177840.
  17. 1 2 Johnson C (27 August 2017). "Major drug study opens up vast new opportunities in combating heart disease". The Washington Post .
  18. ↑ Aday AW, Ridker PM (2018). "Antiinflammatory Therapy in Clinical Care: The CANTOS Trial and Beyond". Frontiers in Cardiovascular Medicine. 5: 62. doi: 10.3389/fcvm.2018.00062 . PMC   5996084 . PMID   29922680.
  19. ↑ Chabner BA, Nabel CS (June 2018). "Canakinumab and Lung Cancer: Intriguing, but Is It Real?". The Oncologist. 23 (6): 637–638. doi: 10.1634/theoncologist.2018-0116 . PMC   6067938 . PMID   29666299.
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