Subject: Ilaris (canakinumab) for Systemic Juvenile Original Effective Date: 4/24/2015 Idiopathic Arthritis (SJIA) Policy Number: MCP-246 Revision Date(s): Review Date(s): 12/15/2016; 6/22/2017 DISCLAIMER This Medical Policy is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this Molina medical coverage policy (MCP) document and provide the directive for all Medicare members. SUMMARY This policy addresses the coverage of Ilaris (canakinumab) for the treatment of Systemic Juvenile Idiopathic Arthritis (SJIA) when appropriate criteria are met. ∑ PREFERRED AGENT for the treatment of Systemic Juvenile Idiopathic Arthritis (SJIA): Actemra (tocilizumab) ∑ Due to the lack of evidence regarding the safety and efficacy of Ilaris (canakinumab) in comparison to other biologic treatments for SJIA, the most cost-effective agent will be preferred: Actemra (tocilizumab) ∑ Consensus guidelines from the Childhood Arthritis Rheumatology and Research Alliance recommend the use of both Actemra (tocilizumab) and Kineret (anakinra) in the management of SJIA.A ‹ Actemra (tocilizumab) is a biologic agent that is also FDA-approved for the treatment of SJIA. It has also been shown to improve ACR 30 response in patients with SJIA. ‹ Kineret (anakinra) is a subcutaneously administered biologic medication used for the treatment of SJIA. It has also been shown to improve ACR 30 response. ‹ Based on the American College of Rheumatology guidelines for the treatment of systemic juvenile idiopathic arthritis,B anakinra is effective and is recommended as initial therapy2,3 or as adjunct therapy in children and adolescents with systemic juvenile idiopathic arthritis in whom an adequate trial of glucocorticoids and/or or nonsteroidal anti-inflammatory drugs (NSAIDs) has failed2,4; additional trials may be necessary to further define the role of anakinra in this condition.d Page 1 of 12 ∑ 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 In September 2013, the ACR released updated guidelines for the treatment of systemic JIA, which included the medications canakinumab, rilonacept, and tocilizumab.B These guidelines include the following treatment recommendations: ‹ For systemic JIA with active systemic features and varying degrees of synovitis, initial treatment for most patients should consist of anakinra with systemic glucocorticoids ‹ For systemic JIA without active systemic features and with varying degrees of active synovitis, initial treatment should be methotrexate or leflunomide for an active joint count higher than 4, with a change to abatacept, anakinra, a tumor necrosis factor (TNF)-α inhibitor, or tocilizumab if disease activity continues after 3 months; for patients with 4 or fewer active joints, NSAID monotherapy or intra-articular glucocorticoid injections should be initial treatment ‹ For systemic JIA with features suggesting macrophage activation syndrome (MAS), initial treatment should include anakinra, a calcineurin inhibitor, or systemic glucocorticoid monotherapy for up to 2 weeks FDA INDICATIONS Systemic juvenile idiopathic arthritis: For the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients � 2 years and older. � NOTE: Ilaris (canakinumab) for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial � Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) is not addressed in the policy. Refer to � MCP-110. � Available as: Ilaris 180mg vials (powder for subcutaneous injection) in a single-use 6 ml glass vial FDA Approved: FCAS and MWS in June 2009; Systemic juvenile idiopathic arthritis in May 2013 Black Box Warnings: None at the time of this writing CLASSIFICATION: Immune Modulator; Monoclonal Antibody; Interleukin-1B blocker Page 2 of 12 RECOMMENDATIONS/COVERAGE CRITERIA Ilaris (canakinumab) may be authorized for members who meet ALL of the following criteria [ALL] 1. � Prescriber specialty [ONE] ¶ Prescribed by, or in consultation with, a board-certified rheumatologist, pediatric rheumatologist or physician experienced in the management of systemic juvenile idiopathic arthritis (SJIA). Submit consultation notes if applicable. 2. � Diagnosis/Indication [ONE] Clinical documented diagnosis of (includes clinical notes from the member’s medical records including any applicable labs and/or tests, supporting the diagnosis): ¶ Active systemic juvenile idiopathic arthritis (SJIA) with disease activity 3. � Age/Gender/Other restrictions [ALL] ¶ 2 years of age or older ‹ The safety and effectiveness of canakinumab in patients younger than 2 years have not been established. ¶ Tuberculin skin test (TST) or Centers for Disease Control (CDC)-recommended equivalent: Screening test must be negative. If test is positive, start treatment for TB prior to starting canakinumab. Documentation required. ‹ Screen all patients for TB prior to initiation and treat latent TB before starting Ilaris therapy. 4. � Step/Conservative Therapy/Other condition Requirements [ALL] ß Member meets ONE (1) of the following: [A or B] A. � New member to Molina Healthcare and stabilized on Ilaris (canakinumab) with a documented positive response or improvement as evaluated the member and Prescriber, such as: [ALL APPLICABLE] û Improvement in serum C reactive protein and signs and symptoms of SJIA (e.g., time between flare-ups and number of joints with active arthritis and limited range of motion) û Resolution of fevers; improvement in limitation of motion; less joint pain or tenderness; decreased duration of morning stiffness or fatigue û Improved function or activities of daily living û Reduced dosage of corticosteroids û Functional ability (Childhood Health Assessment Questionnaire – CHAQ) Page 3 of 12 B. � Documentation of inadequate response, intolerance, or contraindication to the following: [ALL] û At least ONE (1) oral systemic agent for SJIA [ONE] o Glucocorticoid (oral or IV) o Nonsteroidal anti-inflammatory drugs (NSAIDs) o Methotrexate, leflunomide, or sulfasalazine ‹ Ilaris (canakinumab) May be used alone or in combination with corticosteroids, methotrexate (MTX), or NSAIDs. û Actemra (tocilizumab) ‹ FDA approved for the treatment of active systemic juvenile idiopathic arthritis in patients 2 years and older. ¶ Member is NOT concurrently taking another biologic agent for an inflammatory condition, such as: [ANY] û Tumor Necrosis Factor [TNF] blocking agents [i.e. Cimzia (certolizumab pegol), Enbrel, Humira, Remicade (infliximab infusion), Simponi (golimumab), Simponi Aria (golimumab for IV infusion)] û IL-1 inhibitor , IL-6 inhibitor, IL-12/23: Kineret (anakinra), Actemra (tocilizumab), Stelara û Janus kinase inhibitors (i.e. Xeljanz [tofacitinib citrate]) û Other biologics: Orencia (abatacept), Rituxan NOTE: Molina staff: Verify pharmacy claims data for drug names within the last 30 days, OR for new members to Molina Healthcare, confirm drug names in medical chart history 5. � Contraindications/Exclusions/Discontinuations Authorization will not be granted if ANY of the following conditions apply [ANY] ¶ Non-FDA approved indications ¶ Hypersensitivity to canakinumab or any of the excipients ‹ Symptoms of underlying disease may mimic symptoms of hypersensitivity. ¶ Concurrent Biologic Therapy. Ilaris should not be administered in combination with another biologic agent for an inflammatory condition [e.g., tumor necrosis factor (TNF) blocking agents [e.g., Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Simponi (golimumab), Simponi Aria (golimumab)], Kineret (anakinra), or Arcalyst ‹ May increase the risk of serious infections. ‹ Tumor necrosis factor (TNF) antagonist include adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi and Simponi Aria), and infliximab (Remicade) ¶ Concomitant use with live vaccines ‹ Adult and pediatric patients should be brought up to date with all immunizations prior to starting canakinumab therapy. ¶ Latent or active tuberculosis (TB) ‹ There is increased risk for developing new TB infection or reactivation of latent