Sunflower Health Plan ILARIS, Canakinumab Form

Canakinumab (Ilaris®) is an interleukin-1 blocker. FDA Approved Indication(s) Ilaris is indicated for the treatment of: • Periodic fever syndromes: o Cryopyrin-associated periodic syndromes (CAPS) in adults and children 4 years of age and older including:  Familial cold autoinflammatory syndrome (FCAS)  Muckle-Wells syndrome (MWS) o Tumor necrosis factor receptor associated periodic syndrome (TRAPS) in adult and pediatric patients o Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) in adult and pediatric patients o Familial Mediterranean fever (FMF) in adult and pediatric patients • Active Still’s disease, including adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older • Gout flares in adults in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Ilaris is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Periodic Fever Syndromes (must meet all): 1. Diagnosis of FCAS, MWS, TRAPS, HIDS/MKD, or FMF; 2. Prescribed by or in consultation with a rheumatologist; 3. Member meets one of the following (a or b): a. FCAS or MWS: Age ≥ 4 years; b. TRAPS, HIDS/MKD, or FMF: Age ≥ 2 years; Page 1 of 11 CLINICAL POLICY Canakinumab 4. Documentation of one of the following (a – e): a. For FCAS, classic signs and symptoms (e.g., recurrent, intermittent fever and rash often exacerbated by exposure to generalized cool ambient temperature) AND functional impairment limiting activities of daily living; b. For MWS, classic signs and symptoms (e.g., chronic fever and rash of waxing and waning intensity, sometimes exacerbated with exposure to generalized cool ambient temperature) AND functional impairment limiting activities of daily living; c. For TRAPS, chronic or recurrent disease activity with history of ≥ 6 flares within the last 12 months; d. For HIDS/MKD, ≥ 3 febrile acute flares within the last 6 months; e. For FMF, active disease with at least one flare per month and one of the following (i or ii): i. Age < 4 years; ii. Failure of a ≥ 6-month trial of colchicine at up to maximally indicated doses unless contraindicated or clinically significant adverse effects are experienced; 5. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized); 6. Dose does not exceed one of the following (a or b): a. FCAS or MWS (i or ii): i. Weight 15 to 40 kg: 3 mg/kg/dose every 8 weeks; ii. Weight > 40 kg: 150 mg every 8 weeks; b. TRAPS, HIDS/MKD, or FMF (i or ii): i. Weight ≤ 40 kg: 4 mg/kg/dose every 4 weeks; ii. Weight > 40 kg: 300 mg every 4 weeks. Approval duration: Medicaid/HIM – 3 months for FCAS or MWS; 6 months for all other indications Commercial – 6 months or to the member’s renewal date, whichever is longer B. Systemic Juvenile Idiopathic Arthritis (must meet all): 1. Diagnosis of SJIA; 2. Prescribed by or in consultation with a dermatologist, rheumatologist, or gastroenterologist; 3. Age ≥ 2 years; 4. Member meets one of the following (a or b): a. Failure of a ≥ 3 consecutive month trial of methotrexate (MTX) or leflunomide at up to maximally indicated doses, unless clinically significant adverse effects are experienced or both are contraindicated; b. Failure of a ≥ 2-week trial of a systemic corticosteroid at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 5. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized); Page 2 of 11 CLINICAL POLICY Canakinumab 6. Dose does not exceed both of the following (a and b): a. 300 mg every 4 weeks; b. 2 vials every 4 weeks. Approval duration: Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer C. Adult-Onset Still’s Disease (must meet all): 1. Diagnosis of AOSD; 2. Prescribed by or in consultation with a rheumatologist or hematologist; 3. Age ≥ 18 years; 4. Member meets one of the following (a or b): a. Failure of a ≥ 3 consecutive month trial of MTX, at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; b. Failure of a ≥ 2-week trial of a systemic corticosteroid at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 5. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized); 6. Dose does not exceed both of the following (a and b): a. 300 mg every 4 weeks; b. 2 vials every 4 weeks. Approval duration: Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer D. Treatment of Acute Gout Flare 1. Diagnosis of acute gout flare; 2. Age ≥ 18 years; 3. Failure of colchicine, unless contraindicated or clinically significant adverse effects are experienced; 4. Failure of a nonsteroidal anti-inflammatory drug (NSAID) used for gout flare (e.g., naproxen, indomethacin, sulindac), unless member has one of the following contraindications (a, b, c, or d): a. Heart failure or uncontrolled hypertension; b. Current use of an anticoagulant (e.g., aspirin, warfarin, low molecular weight heparin, direct thrombin inhibitors, factor Xa inhibitors, clopidogrel); c. Active duodenal or gastric ulcer (not gastroesophageal reflux disease [GERD]); d. Chronic kidney disease with CrCl < 60 mL/min per 1.73 m2; 5. Member meets both of the following (a and b): a. Failure of a corticosteroid used for gout flare, unless contraindicated or clinically significant adverse effects are experienced; b. Repeated courses of corticosteroids are not appropriate (see Appendix D); Page 3 of 11 CLINICAL POLICY Canakinumab 6. Member is currently taking or will be initiating a urate-lowering therapy (e.g., allopurinol, Uloric, or probenecid), unless contraindicated or clinically significant adverse effects are experienced; 7. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized); 8. Dose does not exceed 150 mg per 12 weeks. Approval duration: 3 months E. Other diagnoses/indications (must meet 1 or 2): 1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or 2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. II. Continued Therapy A. Treatment of Acute Gout Flare 1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B); 2. Member is responding positively to therapy; 3. Member is currently prescribed a urate-lowering agent (e.g., allopurinol, Uloric, or probenecid), unless contraindicated or clinically adverse effects are experienced; 4. Previous Illaris dose was administered ≥ 12 weeks prior; 5. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized); 6. Dose does not exceed 150 mg per 12 weeks. Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer Page 4 of 11 CLINICAL POLICY Canakinumab B. All Other Indications in Section I (must meet all): 1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B); 2. Member is responding positively to therapy; 3. Member does not have combination use with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (see Section III: Diagnoses/Indications for which coverage is NOT authorized); 4. If request is for a dose increase, new dose does not exceed one of the following (a, b, or c): a. FCAS or MWS (i or ii): i. Weight 15 to 40 kg: 3 mg/kg/dose every 8 weeks; ii. Weight > 40 kg: 150 mg every 8 weeks; b. TRAPS, HIDS/MKD, FMF, or SJIA (i or ii): i. Weight ≤ 40 kg: 4 mg/kg/dose every 4 weeks; ii. Weight > 40 kg: 300 mg every 4 weeks; c. SJIA or AOSD: 300 mg every 4 weeks. Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer C. Other diagnoses/indications (must meet 1 or 2): 1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or 2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – Page 5 of 11 CLINICAL POLICY Canakinumab CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents; B. Combination use with biological disease-modifying antirheumatic drugs (bDMARDs) or potent immunosuppressants, including but not limited to any tumor necrosis factor (TNF) antagonists [e.g., Cimzia®, Enbrel®, Humira® and its biosimilars, Simponi®, Avsola®, Inflectra®, Remicade®, Renflexis®], interleukin agents [e.g., Arcalyst® (IL-1 blocker), Ilaris® (IL-1 blocker), Kineret® (IL-1RA), Actemra® (IL-6RA), Kevzara® (IL- 6RA), Stelara® (IL-12/23 inhibitor), Cosentyx® (IL-17A inhibitor), Taltz® (IL-17A inhibitor), Siliq™ (IL-17RA), Ilumya® (IL-23 inhibitor), Skyrizi® (IL-23 inhibitor), Tremfya® (IL-23 inhibitor)], Janus kinase inhibitors (JAKi) [e.g., Xeljanz®/Xeljanz® XR, Cibinqo™, Olumiant®, Rinvoq®], anti-CD20 monoclonal antibodies [Rituxan®, Riabni™, Ruxience™, Truxima®, Rituxan Hycela®], selective co-stimulation modulators [Orencia®], and integrin receptor antagonists [Entyvio®] because of the additive immunosuppression, increased risk of neutropenia, as well as increased risk of serious infections. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AOSD: adult-onset Still’s disease CAPS: cryopyrin-associated periodic syndromes FCAS: familial cold autoinflammatory syndrome FDA: Food and Drug Administration FMF: familial Mediterranean fever GI: gastrointestinal HIDS: hyperimmunoglobulin D syndrome JAKi: Janus kinase inhibitors MKD: mevalonate kinase deficiency MTX: methotrexate MWS: Muckle-Wells syndrome NSAID: non-steroidal anti-inflammatory drugs SJIA: systemic juvenile idiopathic arthritis TRAPS: tumor necrosis factor receptor associated periodic syndrome Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose FMF 2.4 mg/day Gout flare 1.8 mg/treatment Varies colchicine (Colcrys®) corticosteroids (e.g., prednisone, methylprednisolone) FMF PO in 1-2 divided doses based on age: Age 4– 6 years: 0.3-1.8 mg/day Age 6 – 12 years: 0.9-1.8 mg/day Age > 12 years: 1.2-2.4 mg/day Gout flare 1.2 mg at first sign of flare, followed by 0.6 mg one hour later SJIA* 0.5 – 2 mg/kg/day PO of prednisone or equivalent Page 6 of 11 CLINICAL POLICY Canakinumab Drug Name Dosing Regimen Dose Limit/ Maximum Dose 20 mg/day leflunomide (Arava®) AOSD* Varies Gout flare Varies SJIA* 10 – 19.9 kg:10 mg PO QD 20- 40 kg: 15 mg PO QD > 40 kg: 20 mg PO QD SJIA* 0.5 – 1 mg/kg/week PO or SC AOSD* 7.5 – 25 mg/week PO or SC 30 mg/week methotrexate (Trexall®, Otrexup®TM, Rasuvo®, RediTrex®, Xatmep®TM, Rheumatrex®) NSAIDs (e.g., naproxen, indomethacin) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. *Off-label Gout flare Varies Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): confirmed hypersensitivity to the active substance or to any of the excipients • Boxed warning(s): none reported Appendix D: General Information • Periodic fever syndromes are a group of rare autoinflammatory diseases that include cryopyrin-associated periodic syndromes (CAPS), tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), and familial Mediterranean fever (FMF). Diagnosis of these diseases can be confirmed by genetic testing. • Three related conditions make up the broader disease known as CAPS: familial cold • auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal- onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic cutaneous articular syndrome (CINCA). While Ilaris is FDA-approved for FCAS and MWS, it is not FDA-approved for use in patients with NOMID/CINCA. Ilaris is the first therapeutic option for TRAPS and HIDS/MKD and the first biologic option for FMF. In FMF, the current standard of care is colchicine, a relatively safe oral therapy indicated in patients ages 4 and up. Colchicine has well-established benefit in FMF and has been used for decades. Although no United States clinical practice guidelines exist for TRAPS, HIDS/MKD, and FMF, the European League Against Rheumatism (EULAR) guidelines for the management of FMF recommend colchicine be initiated at diagnosis for all patients and response to therapy be assessed every 6 months. Page 7 of 11 CLINICAL POLICY Canakinumab • Examples of positive response to therapy: o Periodic fever syndromes (FCAS, MWS, TRAPS, HIDS/MKD, and FMF) include reduction/normalization of: C-reactive protein (CRP) levels, serum amyloid A (SAA) levels, flare frequency, or severity and duration of symptoms (e.g., joint pain, rash, fever/chills, eye pain, fatigue). o SJIA include improvement in: quantitative measures such as physician global assessment of disease activity, parent or patient global assessment of well-being, number of joints with active arthritis, number of joints with limited range of motion, CRP, and functional ability (CHAQ). o AOSD include normalization or improvement in laboratory test results for serum markers of inflammation (e.g., ESR or CRP), sustained improvement in member’s symptoms and disease stability. Chart notes indicating improvement in rash, joint pain and/or swelling and fevers. • Failure of a trial of conventional DMARDs: o Child-bearing age is not considered a contraindication for use of MTX. Each drug has risks in pregnancy. An educated patient and family planning would allow use of MTX in patients who have no intention of immediate pregnancy. o Social use of alcohol is not considered a contraindication for use of MTX. MTX may only be contraindicated if patients choose to drink over 14 units of alcohol per week. However, excessive alcohol drinking can lead to worsening of the condition, so patients who are serious about clinical response to therapy should refrain from excessive alcohol consumption. • Examples where repeated corticosteroids are not appropriate may include, but are not limited to the following: osteoporosis, osteonecrosis, Cushing syndrome, diabetes mellitus, myopathy, glaucoma, congestive heart failure, or peptic ulcer disease. V. Dosage and Administration Indication CAPS (FCAS and MWS) CAPS (TRAPS, HIDS/MKD, FMF) SJIA, AOSD Treatment of gout flares Dosing Regimen Weight > 40 kg: 150 mg SC every 8 weeks Maximum Dose 150 mg/8 weeks Weight ≥ 15 kg to ≤ 40 kg: 2 mg/kg SC every 8 weeks (if inadequate response, may increase to 3 mg/kg) Weight > 40 kg: 150 mg SC every 4 weeks (if inadequate response, may increase to 300 mg every 4 weeks) Weight ≤ 40 kg: 2 mg/kg SC every 4 weeks (if inadequate response, may increase to 4 mg/kg) Weight ≥ 7.5 kg: 4 mg/kg SC (up to a maximum of 300 mg) every 4 weeks 150 mg SC (interval of at least 12 weeks before a new dose) 300 mg/4 weeks 300 mg/4 weeks 150 mg/ 12 weeks Page 8 of 11 CLINICAL POLICY Canakinumab VI. Product Availability • Single-dose vial for injection, solution: 150 mg/mL VII.