Subject:
Canakinumab (Ilaris)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Canakinumab (Ilaris) is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It binds to human IL-1β and neutralizes its activity by blocking its interaction with IL-1 receptors. Canakinumab is expressed in a murine cell line and comprised of two heavy chains and two light chains, with a molecular mass of 145157 Daltons when deglycosylated. The FDA approved indication for canakinumab is the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 4 years of age and older, and Active Systemic Juvenile Idiopathic Arthritis (SJIA) in patients ages 2 years and older.
Cryopyrin-Associated Periodic Syndromes, or CAPS, are a group of rare, inherited conditions that share a number of symptoms in common, including recurrent rash, fever/chills, joint pain, fatigue, and eye pain/redness. There are three related disorders classified as auto-inflammatory diseases that make up CAPS: Familial Cold Auto-inflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID). These conditions may occur alone or as overlapping syndromes. The incidence of CAPS has been reported to be approximately 1 in 1,000,000 people in the United States.
FCAS is a rare, inherited inflammatory disorder characterized by recurrent attacks of rash, fever/chills, joint pain, fatigue, and conjunctivitis, triggered by exposure to cooling temperatures. Onset of FCAS occurs during early childhood or adolescence and persists throughout the patient's life.
MWS is a form of CAPS characterized by recurrent rash, fever/chills, joint pain, fatigue, and eye pain/redness. MWS symptoms are triggered by random, unknown factors and possibly exercise, stress, or cold. MWS is often associated with hearing loss and/or amyloidosis, an accumulation of amyloid protein in organs such as the kidney.
Systemic juvenile idiopathic arthritis (SJIA) is a severe autoinflammatory disease, driven by innate immunity by means of pro-inflammatory cytokines such as interleukin 1β (IL-1β).
Adult onset Still's disease (AOSD) is a rare inflammatory disorder that affected the entire body (systemic disease). The cause of the disorder is idiopathic. It is the adult form of systemic juvenile rheumatoid arthritis.
NOMID, also known as Chronic Infantile Neurologic Cutaneous Articular (CINCA) syndrome, is a rare, congenital, systemic, inflammatory condition distinguished by recurrent rash, fever/chills, joint pain, fatigue, eye pain/redness, and significant central nervous system (CNS) complications. Symptoms of NOMID generally appear shortly after birth. NOMID is the most severe form of CAPS. Canakinumab is not FDA-approved for NOMID.
Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a rare disorder, with a prevalence of approximately one per million. It is inherited in an autosomal dominant fashion with incomplete penetrance. The genetic defect in TRAPS resides in the gene that encodes the 55 kDA receptor for tumor necrosis factors. Clinical manifestation includes recurrent fever over months or years in the absence of associated viral or bacterial infections. Other features include focal myalgia, conjunctivitis, periorbital edema, abdominal pain and rash.
Hyperimmunoglobulin D syndrome (HIDS) is a rare, autosomal recessive genetic disorder characterized by recurrent febrile episodes typically associated with lymphadenopathy, abdominal pain and an elevated serum polyclonal immunoglobulin D (IgD) level.
Familial Mediterranean Fever is a hereditary auto-inflammatory disorder characterized by recurrent bouts of fever and serosal inflammation. Most patients with FMF experience their first attack in early childhood. The initial attack occurs before the ages of 10 and 20 years in 65 and 90 percent of cases. The onset of pain and fever is usually abrupt, peaking soon after onset.
Policy:
(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
I. Prior to starting therapy with canakinumab the following must be documented:
- Patient is not using a tumor necrosis factor blocking agent (e.g. adalimumab, etanercept and infliximab) AND
- The prescriber is a specialist in the area of the patient's diagnosis (e.g. rheumatologist) or has consulted with a specialist in the area of the patient's diagnosis
II. Canakinumab (Ilaris) is considered medically necessary for the treatment of the following FDA-approved indications:
- Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 4 years of age and older when the following criteria are met:
- Member has genetic documentation of an CIAS1 (NLRP3) mutation based on DNA sequencing; AND
- Member has documented baseline serum levels of inflammatory proteins (C-reactive protein and/or Serum Amyloid A); AND
- Member has two or more of any of the following CAPS-typical symptoms:
· Urticaria-like rash
· Cold-triggered episodes
· Sensonineural hearing loss
· Musculoskeletal symptoms
· Chronic aseptic meningitis
· Skeletal abnormalities
2. Treatment of Active Still's disease, including Adult-Onset Still's Disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 years and older
[INFORMATIONAL NOTE: As per the FDA labeled package insert clinical trials section, the efficacy of Ilaris in adults with AOSD is based on the pharmacokinetic exposure and extrapolation of the established efficacy of Ilaris in SJIA patients. Efficacy of Ilaris was also assessed in a randomized, double-blind, placebo-controlled study that enrolled 36 patients (22 to 70 years old) diagnosed with AOSD. The efficacy data were generally consistent with the results of a pooled efficacy analysis of SJIA patients.]
3. Treatment of Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients 2 years and older when the following criteria are met:
- Current or recurrent disease activity defined as 6 flare ups a year AND
- Confirmed with a mutation of the TNFRSF1A gene
.; AND
- Documented baseline serum levles of C-reactive protein (CRP)
4. Treatment of Hyperimmunoglobulin D syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients 2 years and older when the following criteria are met:
- Diagnosis of HIDS and MKD is confirmed by genetic MVK/enzymatic findings; AND
- Member has a documented prior history of greater than or equal to 3 febrile acute flares within a 6-month period
5. Treatment of Familial Mediterranean Fever (FMF) in adult and pediatric patients 2 years and older when the following criteria are met:
- Genetic confirmation of either homozygous or compound heterozygous; AND
- Treatment with colchicine was ineffective, not tolerated, or is contraindicated
.; AND
- Member has active disease defined as at least one flare per month AND baseline CRP >10mg/L
[INFORMATIONAL NOTE: Use of canakinumab with TNF inhibitors may result in an increased risk of srious infections and an increased risk of neutropenia. Patients should be cautioned not to receive cananakinumab if they have a chronic or active infection, including HIV, Hepatitis B, or Hepatitis C.
As per the FDA approved package insert, live vaccines should not be given at the same time as canakinumab, as there is no data on efficacy or safety. It is recommended that adult and pediatric patients get the pneumococcal and inactivated influenza vaccine.
Macrophage activation syndrome (MAS) is a life-threatening disorder that can develop in patients with SJIA. It should be treated aggressively. Physicians should pay attention to signs of infection of worsening SJIA because these are known triggers of MAS. Eleven cases of MAS were observed in 201 SJIA patients treated with canakinumab in clinical trials. However, no definitive conclusion has been reached.]
III. When canakinumab (Ilaris) is considered medically necessary, initial therapy will be eligible at the FDA approved doses indicated below for a period of 12 months:
1. Cryopyrin-Associated Periodic Syndromes
- Body weight greater than 40 kg - 150 mg every 8 weeks subcutaneously.
- Body weight between 15 kg to 40 kg - 2 mg/kg every 8 weeks subcutaneously.
- Body weight between 15 kg to 40 kg with an inadequate response – dose can be increased to 3 mg/kg every 8 weeks subcutaneously.
2. Still's Disease (Adult onset Still's Disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (SJIA))
- Body weight greater than or equal to 7.5 kg - 4 mg/kg (with a maximum of 300mg) subcutaneously every 4 weeks.
3. Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS)/ Hyperimmunoglobulin D syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)/ Familial Mediterranean Fever (FMF)
- Body weight less than or equal to 40 kg - 2mg/kg every 4 weeks and dose can be increases to 4mg/kg every 4 weeks if the clinical response is not adequate
- Body weight greater than 40 kg -150 mg every 4 weeks and dose can be increased to 300 mg every 4 weeks if clinical response is not adequate
IV. Continued therapy will be considered annually if the member meets ALL of the following criteria:
- Member continues to meet initial criteria; AND
- There is absence of unacceptable toxicity from the drug, including severe hypersensitivity reactions, serious infections, and macrophage activation syndrome; AND
- For Cryopyrin-Associated periodic syndromes
- Disease response as indicated by improvement in member’s symptoms from baseline and/or improvements in serum levels of CRP and/or SAA from baseline; OR
- For Still's Disease (Adult onset Still's Disease (AOSD) and Systemic Juvenile Idiopathic Arthritis (SJIA))
- Disease response as indicated by improvement in signs and compared to baseline such as the number of tender and swollen joint counts; OR
- For Tumor Necrosis Factor Receptor associated periodic syndrome, Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency; or Familial Mediterranean Fever
- Disease response as indicated by improvement in member’s symptoms from baseline and/or improvement of serum levels of CRP
V. Other uses of canakinumab (Ilaris) are considered investigational, including but not limited to Neonatal Onset Multisystem Inflammatory disease (NOMID)/ Chronic Infantile Neurological, Cutaneous and Articular Syndrome (CINCA) gout, osteoarthritis, chronic obstructive pulmonary disease (COPD), and type 1 and 2 diabetes, chronic systolic heart failure, active hyper –IgD syndrome, urticaria, pyoderma gangrenosum, Schnitzler syndrome, acute gouty arthritis, atherosclerosis proliferative diabetic retinopathy, dry eyes, rheumatoid arthritis, majeed syndrome, periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA), pulmonary sarcoidosis, urticarial vasculitis, acute coronary syndrome, breast cancer, colorectal cancer, non-small lung cancer, inflammatory dermatosis, ocular diseases, osteomyelitis, peripheral artery disease, polymyalgia rheumatic, and pulmonary sarcoidosis.
[INFORMATIONAL NOTE: On June 21, 2011, the FDA’s Arthritis Advisory Committee has voted against approval of canakinumab for the treatment of acute gout flares in patients who do not respond to nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine, saying that it had too many concerns about safety.]
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specifically for this drug. Per Local Coverage Article A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Therefore, Medicare Advantage Products will cover Canakinumab (Ilaris) when the Horizon BCBSNJ policy criteria is met AND the drug is furnished and administered by a licensed medical provider as part of a physician service.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Canakinumab (Ilaris)
Ilaris (Canakinumab)
References:
1. Canakinumab (Ilaris) [Prescribing Information]. Novartis Pharmaceuticals Corporation. East Hanover, NJ: June 2020.
2. Canakinumab (Ilaris) [Formulary Dossier]. Novartis Pharmaceuticals Corporation. East Hanover, NJ: 6/1/2009.
3. Capscommunity. Healthcare Professional: Disease Information. Available at http://www.capscommunity.com/caps_forhcp.html. Accessed 8/18/2009.
4. Canakinumab (Ilaris). Micromedex. DrugDex Evaluations. Updated 01/31/2013.Available at http://www.thomsonhc.com. Accessed January 2019.
5. ClinicalTrials.Gov . Canakinmumab. U.S National Institutes of Health. Available from: http://clinicaltrials.gov/ct2/results?term=canakinumab. Accessed January 2019.
6. Ringold S, Weiss PF, Beukelman T, DeWitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Nigrovic PA, Robinson AB, and Vehe RK. 2013 update of the 2011 American college of rheumatology recommendations for the treatment of juvenile idiopathic arthritis. Arthritis & Rheumatism. 2013;65(10):2499-2512.
7. `Hull KM, Drewe E, Aksentijevich I, et al. The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 2002; 81:349.
8. Lidar M, Yaqubov M, Zaks N, et al. The prodrome: a prominent yet overlooked pre-attack manifestation of familial Mediterranean fever. J Rheumatol 2006; 33:1089.
9. Petty RE, Southwood TR, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004; 31:390.
10. Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016; 75:644.
11. UpToDate. Management of familial Mediterranean fever. Literature review current through: January 2018. Topic last updated: April 2017. Available at: https://www.uptodate.com/contents/management-of-familial-mediterranean-fever. Accessed February 2018.
12. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017 Jun;76(6):942-947.
13. Henderson LA. A Bullseye for Children with Systemic Juvenile Idiopathic Arthritis. Editorial article: doi:10.1002/art/40867.
14. Haar NM, Dijkhuizen PV, et al. Treat-to-target using first-line recombinant interleukin-1 receptor antagonist monotherapy in new-onset systemic juvenile idiopathic arthritis: results from a five year follow-up study. 2019. The Authors Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
15. Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non‐Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care & Research, vol. 71, no. 6, 2019, pp. 717–734., doi:10.1002/acr.23870.
16. Clinicaltrials.gov. Ilaris. https://clinicaltrials.gov/ct2/results?cond=ilaris&term=&cntry=&state=&city=&dist=. Accessed January 2020.
17. Pubmed. Canakinumab. https://www.ncbi.nlm.nih.gov/pubmed/?term=ilaris Accessed January 2020.
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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