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canakinumab (Ilaris)

Indications: - hereditary periodic fever syndrome - cryopyrin-associated periodic syndromes a) familial cold autoinflammatory syndrome (FCAS) b) Muckle-Wells Syndrome (MWS) - colchicine-resistant familial Mediterranean fever [8] - familial hibernian fever (TRAPS) - hyper IgD syndrome (mevalonate kinase deficiency) - juvenile idiopathic arthritis [3] - Still's disease [11] - may reduce risk of gout flares in post MI patients [9] - treatment of gout flares in adults with contraindications to NSAIDs, colchicine, or repeated courses of glucocorticoids (FDA-approved) [14] - may risk of recurrent major cardiovascular events* [4] - may reduce risk of lung cancer & lung cancer mortality [4,5] - may reduce progression of osteoarthritis [12] * no effect of serum cholesterol [4] Contraindications: - does not prevent progression of prediabetes to type 2 diabetes [7] - not approved for prevention of recurrent myocardial infarction in patients with heart failure - does not increase likelihood of survival without mechanical ventilation [13] Pregnancy category: C [2] Dosage: - subcutaneous injection every 8 weeks - 150 mg patients with body weight greater than 40 kg - 2 mg/kg with body weight 15-40 kg - may increase to 3 mg/kg if inadequate response to 2 mg/kg - 150 mg every 3 months for 15% cardiovascular risk reduction [4] - 300 dose failed to meet prespecified threshold for benefit [4] - 50 mg dose not effective [4] - 300 mg every 3 months associated with 77% reduction in fatal lung cancer [4] Sterile, single-use 6-mL, glass vial containing 180 mg of Ilaris lyophilized powder for reconstitution Monitor: - complete blood count (CBC) at baseline & every 3 months [2] Adverse effects: - nasopharyngitis, diarrhea, influenza, headache, nausea - increase in deaths due to infection (0.31 vs 0.18 for placebo per 100 person-years) [4,6] Mechanism of action: - fully humanized monoclonal antibody - interleukin-1 beta antagonist [2] Notes: - cost of canakinumab U.S. 2017 is ~ $65,000-200,000/year [4] Management: - whenever possible bring patients up to date on vaccinations prior to initiating biologic immunosuppressive agent [2]

Interactions

drug adverse effects of immunosuppressive agents monitor with immunosuppressive agents

Related

interleukin-1; lymphocyte-activating factor (IL1)

General

biologic immunosuppressive agent (biologic agent, biologic immune modulator) pharmaceutical monoclonal antibody

References

  1. Prescriber's Letter 17(2): 2010 New Drugs Approved by the FDA in 2009 Detail-Document#: 260213 (subscription needed) http://www.prescribersletter.com
  2. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18, 19. American College of Physicians, Philadelphia 2012, 2015, 2018, 2022.
  3. Deprecated Reference
  4. Wendling p CANTOS: Anti-Inflammatory Drug Cuts CV Events, Cancer Medscape - Aug 27, 2017 http://www.medscape.com/viewarticle/884745 - Ridker PM, Everett BM, Thuren T et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017 Aug 27; PMID: 28845751 http://www.nejm.org/doi/10.1056/NEJMoa1707914 - Harrington RA. Targeting inflammation in coronary artery disease. N Engl J Med 2017 Aug 27 PMID: 28844177 http://www.nejm.org/doi/10.1056/NEJMe1709904
  5. Ridker PM, MacFadyen JG, Thuren T, et al Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo- controlled trial. Lancet. 2017 Aug 25. pii: S0140-6736(17)32247-X. PMID: 28855077
  6. Ridker PM, Everett BM, Thuren T et al Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med 2017; 377:1119-1131. September 21, 2017 PMID: 28845751 Free full text http://www.nejm.org/doi/full/10.1056/NEJMoa1707914
  7. Wendling P CANTOS: Canakinumab Fails to Prevent New-Onset Diabetes. Medscape - Mar 14, 2018. https://www.medscape.com/viewarticle/893887
  8. De Benedetti F, Gattorno M, Anton J et al Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. N Engl J Med 2018; 378:1908-1919. May 17, 2018 PMID: 29768139 https://www.nejm.org/doi/full/10.1056/NEJMoa1706314
  9. Walsh N IL-1 Blockade Appears Effective Against Gout. Canakinumab lowered the risk of attacks by more than half in post-MI patients. MedPage Today. June 14, 2018 https://www.medpagetoday.com/meetingcoverage/eular/73503 - Solomon D et al Serum urate, gout, and cardiovascular disease in a randomized controlled trial of canakinumab: a CANTOS secondary analysis. European Congress of Rheumatology (EULAR) 2018; abstract OP0014.
  10. NEJM J Watch editors Anti-inflammatory Agent Rejected as Heart Disease Drug. David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  11. Medscape. Aug 14, 2020 FDA Drug Approvals, Internal Medicine - 2020 Midyear Review. https://reference.medscape.com/viewarticle/935373
  12. Schieker M et al. Effects of interleukin-1beta inhibition on incident hip and knee replacement: Exploratory analyses from a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2020 Aug 4; PMID: 32744862 https://www.acpjournals.org/doi/10.7326/M20-0527
  13. Caricchio R, Abbate A, Gordeev I et al Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19. A Randomized Clinical Trial. JAMA. 2021;326(3):230-239 PMID: 34283183 https://jamanetwork.com/journals/jama/fullarticle/2782185
  14. Hicks L FDA Approves Canakinumab for Gout Flares. Medscape. August 30, 2023 https://www.medscape.com/viewarticle/995993
  15. HIGHLIGHTS OF PRESCRIBING INFORMATION ILARIS (canakinumab) for subcutaneous injection https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/ilaris.pdf