Pegloticase (Krystexxa) Form

Pegloticase (Krystexxa®) is a PEGylated uric acid specific enzyme. FDA Approved Indication(s) Krystexxa is indicated for the treatment of chronic gout in adult patients refractory to conventional therapy. Limitation(s) of use: Krystexxa is not recommended for the treatment of asymptomatic hyperuricemia.
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 Krystexxa is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Gout (must meet all):

1. Diagnosis of chronic gout;
2. Age ≥ 18 years;

3. Positive for symptomatic gout with one or more of the following: a. At least 3 gout flares in the previous 18 months; b. At least 1 gout tophus; c. Chronic gouty arthritis;

   4. Failure to normalize uric acid to < 6 mg/dL with allopurinol and febuxostat at maximally indicated doses, each used for at least 3 months unless clinically significant adverse effects are experienced or both are contraindicated;
   5. Failure of one uricosuric agent (e.g., probenecid or losartan), at maximally indicated doses, in combination with allopurinol or febuxostat unless clinically significant adverse effects are experienced or all are contraindicated;
   6. Krystexxa is not prescribed concurrently with oral urate-lowering agents (e.g., allopurinol, febuxostat, probenecid);
   7. Dose does not exceed 8 mg (uricase protein) every two weeks. Approval duration:
      Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer Page 1 of 6

   CLINICAL POLICY Pegloticase B. 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. Chronic Gout (must meet all):
   3. 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);
   4. Member is responding positively to therapy as evidenced by a decrease in plasma uric acid levels;
   5. Krystexxa is not prescribed concurrently with oral urate-lowering agents (e.g., allopurinol, febuxostat, probenecid);
   6. If request is for a dose increase, new dose does not exceed 8 mg (uricase protein) every two weeks. Approval duration:
      Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):
   7. 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 Page 2 of 6

   CLINICAL POLICY Pegloticase 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 2 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.
      IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration G6PD: glucose-6-phosphate dehydrogenase 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 800 mg/day 80 mg/day 2 gm/day allopurinol (Zyloprim) Uloric (febuxostat) probenecid
      100 mg PO QD; may be increased by 100 mg every 2 to 4 weeks until serum urate concentration is ≤ 6 mg/dL or until maximum of 800 mg/day is reached
      40 mg PO QD 250 mg PO BID for the first week, then 500 mg PO BID
      losartan (Cozaar) 50 mg PO QD 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 50 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): glucose-6-phosphate dehydrogenase (G6PD) deficiency • Boxed warning(s): anaphylaxis and infusion reactions; G6PD deficiency-associated hemolysis and methemoglobinemia Page 3 of 6

   CLINICAL POLICY Pegloticase V. Dosage and Administration
   Indication Chronic gout Dosing Regimen 8 mg IV every 2 weeks, co-administered with weekly PO methotrexate 15 mg. Krystexxa alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate
   Maximum Dose 8 mg/2 weeks VI. Product Availability
   Vial: 8 mg of uricase protein/1 mL VII.