Interleukin-1 Inhibitors (Arcalyst, Ilaris, Kineret)

POLICY NUMBER

L.5.01.485

Arcalyst (rilonacept)

Ilaris (canakinumab)

Kineret (anakinra)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Interleukin-1 (IL-1) is a key cytokine that mediates the pathophysiology of many inflammatory processes. Pharmacologic inhibitors of IL-1 are used in the treatment of various inflammatory and autoimmune disease.

Arcalyst (rilonacept) is an interleukin-1 blocker indicated for the treatment of CAPS, including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older for the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weight at least 10kg, and for the treatment of recurrent pericarditis and reduction in risk of recurrence in adults and pediatric patients 12 years and older.

Ilaris (canakinumab) is a monoclonal antibody that binds to interleukin-1B to neutralize its activity by blocking its interaction with IL-1 receptors. Ilaris (canakinumab) is indicated for the treatment of the following autoinflammatory Periodic Fever Syndromes: CAPS, in adults and children 4 years of age and older (including FCAS and MWS), Tumor Necrosis Factor (TNF) Receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients, Hyperimmunoglobulin D (Hyper-IgD) Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients, and Familial Mediterranean Fever (FMF) in adult and pediatric patients. Ilaris (canakinumab) is also indicated for the treatment of active Still’s Disease, including Adult-Onset Still’s Disease (AOSD) and Systemic Juvenile Idiopathic arthritis (SJIA) in patients 2 years and older and for the symptomatic treatment of adult patients with gout flares in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.

Kineret (anakinra) is an interleukin-1 receptor antagonist indicated for the treatment of a form of CAPS called Neonatal-Onset Multisystem Inflammatory Disease (NOMID) and active rheumatoid arthritis in patients 18 years of age and older who have failed 1 or more disease modifying antirheumatic drugs (DMARDs), and for the treatment of Deficiency of Interluekin-1 Receptor Antagonist (DIRA).

Related medical policies -

• Anti-Rheumatic Biologicals

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

 Initial Evaluation

Arcalyst (rilonacept), Ilaris (canakinumab), or Kineret (anakinra) may be considered medically necessary when ALL of the following criteria are met:

1. ONE of the following:

   1. The request is for Arcalyst (rilonacept) and ONE of the following:

      1. The individual has a documented diagnosis of Cryopyrin-Associated Periodic Syndrome (CAPS), Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS) andALL of the following:

         1. The individual is at least 12 years of age; AND

         2. ALL of the following:

            1. The individual has laboratory evidence of a genetic mutation in the Cold-Induced Auto-inflammatory Syndrome 1 (CIAS1), also known as NLRP3;

            2. The 

               individual

               has elevated 

               pretreatment serum

               inflammatory markers (C-reactive protein and serum amyloid A)

               ; AND

            3. The individual has

               at least TWO of the following 

               symptoms

               typical 

               for

               CAPS:

               1. Urticaria-like rash;

               2. Cold-triggered episodes;

               3. Sensorineural hearing loss;

               4. Musculoskeletal symptoms of arthralgia/arthritis/myalgia;

               5. Chronic aseptic meningitis; OR

               6. Skeletal abnormalities of epiphyseal overgrowth/frontal bossing;

      2. The individual has a documented diagnosis of deficiency of interleukin-1 receptor antagonist (DIRA) and ALL of the following:

         1. The individual weighs at least 10kg;

         2. The individual has laboratory evidence of genetic mutation in the IL1RN gene; AND

         3. The requested agent is being used for maintenance of remission; OR

      3. The individual has a documented diagnosis of recurrent pericarditis and ALL of the following:

         1. The individual is at least 12 years of age;

         2. The individual has had at least two episodes of pericarditis separated by a symptom-free interval of at least four- to six-weeks;

         3. ONE of the following:

            1. BOTH of the following:

               1. The individual has tried and had an inadequate response to at least a 6-month trial of colchicine; AND

               2. Colchicine was used concomitantly with at least a 1 week trial of a non-steroidal anti-inflammatory drug (NSAID) AND a corticosteroid; OR

            2. The individual has tried and had an inadequate response to an oral immunosuppressant (i.e., azathioprine, methotrexate, mycophenolate) used in the treatment of recurrent pericarditis;

   2. The request is for Ilaris (canakinumab) and ONE of the following:

      1. The individual has a diagnosis of Cryopryin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) and ALL of the following:

         1. The individual is at least 4 years of age; AND

         2. ALL of the following:

            1. Laboratory evidence of a genetic mutation in the Cold-Induced Auto-inflammatory Syndrome 1 (CIAS1), also known as NLRP3;

            2. The

               individual

               has elevated 

               pretreatment serum

               inflammatory markers (C-reactive protein and serum amyloid A)

               ; AND

            3. The individual has

               at least TWO of the following 

               symptoms

               typical 

               for

               CAPS:

               1. Urticaria-like rash;

               2. Cold-triggered episodes;

               3. Sensorineural hearing loss;

               4. Musculoskeletal symptoms of arthralgia/arthritis/myalgia;

               5. Chronic aseptic meningitis; OR

               6. Skeletal abnormalities of epiphyseal overgrowth/frontal bossing;

      2. The individual has a documented diagnosis of Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) and ALL of the following: 

         1. The individual is at least 2 years of age;

         2. The individual has a genetic mutation in the tumor necrosis factor receptor-1 (TNFR1) gene (TNFRSF1A);

         3. The individual has chronic or recurrent disease (defined as >6 flares per year); AND

         4. The individual has documented baseline serum level of C-Reactive Protein (CRP);

      3. The individual has a documented diagnosis of Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) and ALL of the following:

         1. The individual is at least 2 years of age;

         2. The diagnosis of HIDS/MKD was confirmed by ONE of the following:

            1. Pathogenic mutation in the MVK gene; OR

            2. Elevated serum IgD levels;

         3. The individual has a documented history of at least three (3) febrile episodes within a 6 month period; AND

         4. The individual has documented baseline serum level of C-Reactive Protein (CRP);

      4. The individual has a documented diagnosis of Familial Mediterranean Fever (FMF) and ALL of the following:

         1. The individual is at least 2 years of age;

         2. The individual has at least one known MEFV exon 10 mutation;

         3. The individual has failed colchicine therapy or has a documented intolerance or allergy;

         4. The individual has active disease defined as at least one febrile episode per month; AND

         5. The individual has documented baseline serum levels of C-Reactive Protein (CRP); OR

      5. The individual has a documented diagnosis of Still’s Disease (Adult-Onset Still’s Disease [AOSD] and Systemic Juvenile Idiopathic Arthritis [SJIA]) and ALL of the following:

         1. ONE of the following:

            1. The individual is at least 18 years of age with active Adult-Onset Still’s Disease; OR

            2. The individual is at least 2 years of age with active Systemic Juvenile Idiopathic Arthritis; AND

         2. ONE of the following:

            1. The individual has tried and had an inadequate response or intolerance to a conventional treatment (i.e., systemic glucocorticoid or oral non-steroidal anti-inflammatory drugs [NSAIDs]); OR

            2. The individual’s medication history indicates use of another biologic immunomodulator agent that is FDA labeled or supported in compendia for the treatment of AOSD or SJIA; OR

   3. The request is for Kineret (anakinra) and ONE of the following:

      1. The individual has a documented diagnosis of Neonatal-Onset Multisystem Inflammatory Disease (NOMID), also known as chronic infantile neurologic cutaneous and articular (CINCA) syndrome; OR

      2. The individual has a documented diagnosis of deficiency of interleukin-1 receptor antagonist (DIRA) with laboratory evidence of genetic mutation in the IL1RN gene;

2. The prescriber is a specialist in the area of the individual’s diagnosis (e.g., allergist, cardiologist, immunologist, pediatrician, rheumatologist) or has consulted with a specialist in the area of the individual’s diagnosis;

3. The individual will NOT be using the requested agent in combination with another immunomodulatory agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors);

4. The individual does NOT have any FDA labeled contraindications to the requested agent; AND

5. The prescribed dosage is within the program quantity limit based on FDA approved labeled dosage.

Length of Approval: 6 months

Renewal Evaluation

Arcalyst (rilonacept), Ilaris (canakinumab), or Kineret (anakinra) may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has been previously approved for the requested agent through the BCBSMS PA process;

2. The individual has documented clinical improvement (i.e., slowing of disease progression or decrease in symptom severity and/or frequency);

3. The prescriber is a specialist in area of the individual’s diagnosis (e.g., allergist, cardiologist, immunologist, pediatrician, rheumatologist) or has consulted with a specialist in the area of the individual’s diagnosis;

4. The individual will not be receiving the requested agent in combination with another biologic immunomodulator agent (e.g., TNF inhibitors, JAK inhibitors, IL-4 inhibitors)

   ;

5. The individual does NOT have any FDA labeled contraindications to the requested agent; AND

6. The prescribed dosage is within the program quantity limit based on FDA approved labeled dosage.

Length of Approval: 12 months

Services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medication Failure

Medication failure is defined as disease progression at generally accepted doses at a duration appropriate for the disease state being treated. Dosages below the recommended dose for the specific condition being treated and/or experience of common side effects of medication will not be considered medication failure or lack of response for the purpose of this review.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary. BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [ie, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

BCBSMS determines patient medication trial and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and to submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

04/05/2016: New policy added. Effective 01/01/2016.

05/31/2016: Policy number L.5.01.485 added.

06/13/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

05/16/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

03/27/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

07/23/2019: Code Reference section updated to add HCPCS codes J0638 and J2793.

02/18/2021: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added drug names to the top of the policy. Policy description updated regarding indications for Ilaris and Kineret. Policy section extensively revised to list medically necessary criteria for Arcalyst, Ilaris, and Kineret. Added renewal evaluation criteria. Added statement to state that services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary. Policy Guidelines updated regarding BCBSMS request for medical records, definition for investigative, and BCBSMS review of pharmacy claims data. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants.

07/15/2025: Effective 09/15/2025 - Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy title changed from "Cryopyrin-Associated Periodic Syndromes (CAPS)" to "Interleukin-1 Inhibitors (Arcalyst, Ilaris, Kineret)." Policy description updated regarding indications for Arcalyst (rilonacept), Ilaris (canakinumab), and Kineret (anakinra). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria for Arcalyst (rilonacept), Ilaris (canakinumab), and Kineret (anakinra) extensively revised. Renewal evaluation criteria updated regarding prescriber requirements, biologic immunomodulator agents, FDA labeled contraindications, and dose requirements. Policy Guidelines updated to define medication failure. Sources updated. Policy update effective 09/15/2025.

SOURCE(S)

1. Arcalyst prescribing information. Kiniksa Pharmaceuticals (UK), Ltd. November 2024. Last accessed March 2025.

2. Chiabrando, J, Bonaventura, A, Vecchié, A. et al. Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. JACC. 2020 Jan, 75 (1) 76–92. https://doi.org/10.1016/j.jacc.2019.11.021

3. Ilaris prescribing information. Novartis Pharmaceuticals Corporations. November 2024. Last accessed March 2025.

4. Kineret prescribing information. Swedish Orphan Biovitrum AB (publ). September 2024. Last accessed March 2025.

5. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS) Annals of the Rheumatic Diseases 2017;76:942-947.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

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