ARCALYST, Rilonacept Form

Rilonacept (Arcalyst®) is an interleukin-1 blocker. FDA Approved Indication(s) Arcalyst is indicated for: • Treatment of cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS) in adults and children 12 and older • Maintenance of remission of deficiency of interleukin-1 receptor antagonist (DIRA) in adults and pediatric patients weighing at least 10 kg. • Treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and pediatric patients 12 years and older 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 Arcalyst is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Cryopyrin-Associated Periodic Syndromes (must meet all):

1. Diagnosis of FCAS or MWS;
   2. Prescribed by or in consultation with a rheumatologist;
   3. Age ≥ 12 years;
   4. Documentation of one of the following (a or b): 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;

2. 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 1 of 8

   CLINICAL POLICY Rilonacept

3. Dose does not exceed both of the following (a and b): a. Loading dose (both i and ii): i. 320 mg; ii. Two injections; b. Once weekly dosing (both i and ii): i. 160 mg; ii. Single injection. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Deficiency of Interleukin-1 Receptor Antagonist (must meet all):
4. Diagnosis of DIRA confirmed by presence of loss-of-function ILRN mutations;
   2. Prescribed by or in consultation with a rheumatologist;
   3. Weight ≥ 10 kg;
   4. Member is in remission and has been stable for ≥ 6 months;
   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);
5. Dose does not exceed 4.4 mg/kg (up to 320 mg) once weekly. Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer C. Recurrent Pericarditis (must meet all):
6. Diagnosis of RP with pericarditis that recurs after a symptom-free interval of ≥ 4 weeks after an acute pericarditis episode;
7. Prescribed by or in consultation with a cardiologist or rheumatologist;
   
   3. Age ≥ 12 years;
   4. Member meets one of the following for the recurrent episode (a or b): a. Failure of colchicine in combination with an NSAID (e.g., aspirin, ibuprofen, indomethacin) at up to maximally indicated doses; b. Member has intolerance or contraindication to NSAIDs, and has had a failure of colchicine in combination with a glucocorticoid (e.g., prednisone) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
8. 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);

9. Dose does not exceed both of the following (a and b): a. Loading dose (both i and ii): i. 320 mg; ii. Two injections; b. Once weekly dosing (both i and ii): i. 160 mg; ii. Single injection. Page 2 of 8

   CLINICAL POLICY Rilonacept Approval duration:
   Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer D. Other diagnoses/indications (must meet 1 or 2):

10. 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
11. 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. All Indications in Section I (must meet all):
12. 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);

13. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. For CAPS or RP (both i and ii):
    i. 160 mg once weekly; ii. Single injection once weekly; b. For DIRA: 4.4 mg/kg (up to 320 mg) once weekly. Approval duration:
    Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer Page 3 of 8

    CLINICAL POLICY Rilonacept B. Other diagnoses/indications (must meet 1 or 2):

14. 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

15. 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 – 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 CAPS: cryopyrin-associated periodic syndromes
    DIRA: deficiency of interleukin-1 receptor antagonist FCAS: familial cold autoinflammatory syndrome
    FDA: Food and Drug Administration JAKi: Janus kinase inhibitors
    MWS: Muckle-Wells syndrome RP: recurrent pericarditis Page 4 of 8

    CLINICAL POLICY Rilonacept 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.
    Dosing Regimen Drug Name Dose Limit/ Maximum Dose 3,000 mg/day 2,400 mg/day 150 mg/day 1.2 mg/day aspirin
    ibuprofen (Advil, Motrin) indomethacin (Indocin) colchicine RP: 750 - 1,000 mg PO Q8H RP: 600 - 800 mg PO Q8H RP: 25-50 mg PO Q8H RP: 0.5 -1.2 mg PO in one or divided doses RP: 0.25 - 0.5 mg/kg/day prednisone 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 0.5 mg/kg/day Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Three related conditions make up the broader disease known as CAPS: FCAS, MWS, and neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic cutaneous articular syndrome (CINCA). Arcalyst is not FDA- approved for use in patients with NOMID/CINCA. • DIRA patients are homozygous or compound heterozygous for loss-of-function mutations in IL1RN, encoding IL-1Ra. Most mutations are nonsense or frameshift mutations that lead to either no expression of protein or expression of nonfunctional protein. Examples of disease-causing mutations in IL1RN identified include: 4 nonsense mutations, 1 in-frame deletion, 3 frameshift deletions, and a 22-kb and a genomic 175-kb deletion on chromosome 2.
    • Concomitant administration of Arcalyst with tumor necrosis factor (TNF) inhibitors (e.g., Enbrel, Humira, or Remicade) and interleukin-1 blocking agents (e.g., Kineret) is not recommended because this may increase the risk of serious infections. • Examples of positive response to therapy in CAPS include reduction/normalization of: C- reactive protein levels, serum amyloid A levels, flare frequency, or severity and duration of symptoms (e.g., joint pain, rash, fever/chills, eye pain, fatigue). • Do not initiate treatment with Arcalyst in patients with active or chronic infections.
    V. Dosage and Administration
    Indication Dosing Regimen CAPS (FCAS, MWS), RP Age ≥ 18 years: 320 mg SC loading dose followed by 160 mg SC once weekly Maximum Dose Loading dose: 320 mg; Maintenance dose: 160 mg weekly
    Page 5 of 8

    CLINICAL POLICY Rilonacept Indication Dosing Regimen Maximum Dose Age 12 to 17 years: 4.4 mg/kg SC loading dose followed by 2.2 mg/kg SC once weekly Adult patients: 320 mg SC weekly 320 mg/week DIRA Pediatric patients weight ≥ 10 kg:
    4.4 mg/kg up to a maximum of 320 mg, delivered as 1 or 2 injections once weekly VI. Product Availability
    Single-dose vial for reconstitution: 220 mg VII.