Background

Ilaris is a human anti-interleukin-1β (IL-1β) monoclonal antibody that binds to human IL-1β and neutralizes its activity by blocking its interaction with IL-1 receptors.1 It does not bind IL-1α or IL-1 receptor antagonist (IL-1ra). IL-1 cytokine signaling is important in the pathogenesis of autoinflammatory conditions. Ilaris is indicated for the following uses:
1. Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children aged 4 years and older;
2. Active Still’s disease, including Adult-Onset Still’s Disease (AOSD) and Systemic juvenile idiopathic arthritis (SJIA) in patients ≥ 2 years of age;
3. Tumor necrosis factor receptor associated periodic syndrome (TRAPS), in adult and pediatric patients;
4. Hyperimmunoglobulin D Syndrome (HIDS)/mevalonate kinase deficiency (MKD), in adult and pediatric patients; AND
5. Familial Mediterranean Fever (FMF), in adult and pediatric patients.

Policy

The use of Ilaris is MEDICALLY NECESSARY for the treatment of periodic fever syndromes when the following criteria has been met:

1. Diagnosis of one of the following periodic fever syndromes:
   1. Cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS)
   2. Tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS)
   3. Hyperimmunoglobulin D (Hyper-IgD) syndrome (HIDS/mevalonate kinase deficiency (MKD)
   4. Familial mediterranean fever (FMF)
2. Prescribed by or in consultation with one of the following:
   1. Immunologist
   2. Allergist
   3. Dermatologist
   4. Rheumatologist
   5. Neurologist
3. Both of the following:
   1. Patient is not receiving concomitant treatment with Tumor Necrosis Factor (TNF) inhibitors (e.g., Enbrel [etanercept], Humira [adalimumab], Remicade [infliximab])
   2. Patient is not receiving concomitant treatment with Interleukin-1 inhibitor (e.g., Arcalyst [rilonacept], Kineret [anakinra])

The use of Ilaris is MEDICALLY NECESSARY for the treatment of Systemic Juvenile Idiopathic Arthritis (SJIA) when the following criteria has been met:

1. Diagnosis of active systemic juvenile idiopathic arthritis (SJIA)
2. Trial and failure, contraindication, or intolerance to one of the following conventional therapies at maximally tolerated doses:
   1. Minimum duration of a 3-month trial and failure of methotrexate
   2. Minimum duration of a 1-month trial of a nonsteroidal anti-inflammatory drug (NSAID) (e.g., ibuprofen, naproxen)
   3. Minimum duration of a 2-week trial of a systemic glucocorticoid (e.g., prednisone)
3. Both of the following:
   1. Patient is not receiving concomitant treatment with Tumor Necrosis Factor (TNF) inhibitors (e.g., Enbrel [etanercept], Humira [adalimumab], Remicade [infliximab])
   2. Patient is not receiving concomitant treatment with Interleukin-1 inhibitor (e.g., Arcalyst [rilonacept], Kineret [anakinra])
4. Prescribed by or in consultation with a rheumatologist

The use of Ilaris is MEDICALLY NECESSARY for the treatment of Adult-Onset Still’s Disease when the following criteria has been met:

1. Diagnosis of Still’s Disease, including Adult-Onset Still’s Disease (AOSD)
2. Trial and failure, contraindication, or intolerance to one of the following:
   1. Corticosteroids (e.g., prednisone)
   2. Methotrexate
   3. Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen)
3. Both of the following:
   1. Patient is not receiving concomitant treatment with Tumor Necrosis Factor (TNF) inhibitors (e.g., Enbrel [etanercept], Humira [adalimumab], Remicade [infliximab])
   2. Patient is not receiving concomitant treatment with Interleukin-1 inhibitor (e.g., Arcalyst [rilonacept], Kineret [anakinra])
4. Prescribed by or in consultation with a rheumatologist

The use of Ilaris is MEDICALLY NECESSARY for the treatment of gout flares when the following criteria has been met:

1. Diagnosis of gout flares
2. Trial and failure, contraindication, or intolerance to ALL of the following:
   1. Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, naproxen)
   2. Colchicine
   3. Corticosteroids (e.g., prednisone)
3. Patient has not received Ilaris in the last 12 weeks
4. Prescribed by or in consultation with one of the following:
   1. Rheumatologist
   2. Nephrologist

The continued use of Ilaris is MEDICALLY NECESSARY when the following criteria has been met:

1. Documentation of positive clinical response to therapy
2. Both of the following:
   1. Patient is not receiving concomitant treatment with Tumor Necrosis Factor (TNF) inhibitors (e.g., Enbrel [etanercept], Humira [adalimumab], Remicade [infliximab])
   2. Patient is not receiving concomitant treatment with Interleukin-1 inhibitor (e.g., Arcalyst [rilonacept], Kineret [anakinra])

References

1. Ilaris® for subcutaneous injection [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; December 2016.
2. Arcalyst® for injection [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals Inc; September 2016.
3. Hoffman HM, Throne ML, Amar NJ, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58:2443-2452.
4. Shinkai K, McCalmont TH, Leslie KS. Cryopyrin-associated periodic syndromes and autoinflammation. Clin Exp Dermatol. 2008;33:1-9.
5. Ringold S, Weiss PF, Beukelman T, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013;65(10):2499-2512.
6. Ozen S, Hoffman HM, Frenkel J, et al. Familial Mediterranean Fever (FMF) and beyond: a new horizon. Fourth International Congress on the Systemic Autoinflammatory Diseases held in Bethesda, USA, 6-10 November 2005. Ann Rheum Dis. 2006;65(7):961-964.
7. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, et al; Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360:2416-2425.
8. Russo RA, Melo-Gomes S, Lachmann HJ, et al. Efficacy and safety of canakinumab therapy in paediatric patients with cryopyrin-associated periodic syndrome: a single-centre, real-world experience. Rheumatology (Oxford). 2014;53(4):665-670.
9. Kuemmerle-Deschner JB, Hachulla E, Cartwright R, et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011;70(12):2095-2102.
10. Sibley CH, Chioato A, Felix S, et al. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease. Ann Rheum Dis. 2015;74(9):1714-1719.
11. Kuemmerle-Deschner JB, Ramos E, Blank N, et al. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011;13(1):R34.
12. Genetics Home Reference. US National Library of Medicine. Available at: https://ghr.nlm.nih.gov/. Accessed on October 2, 2017. Search terms: TRAPS, familial Mediterranean fever, MKD.
13. Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016;75(4):644-651.
14. ter Haar NM, Oswald M, Jeyaratnam J, et al. Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis. 2015;74(9):1636-1644.
15. Kimura Y, Morgan DeWitt E, Beukelman T, et al. Adding Canakinumab to the Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for Systemic Juvenile Idiopathic Arthritis: comment on the article by DeWitt et al. Arthritis Care Res (Hoboken). 2014;66(9):1430-1431.
16. DeWitt EM, Kimura Y, Beukelman T, et al. Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2012;64(7):1001-1010.
17. Ruperto N, Brunner HI, Quartier P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396-2406.
18. Novartis. Efficacy, safety and tolerability of ACZ885 in patients with active rheumatoid arthritis. In; ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Accessed on October 2, 2017. Available from: http://www.clinicaltrials.gov/ct2/show/NCT00424346?term=acz885&rank=10. NLM Identifier: NCT00424346
19. Alten R, Gomez-Reino J, Durez P, et al. Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. BMC Musculoskelet Disord. 2011;12:153.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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