RXMP-24 Pegloticase (Krystexxa) Form

pegloticase (Krystexxa)

Updated on: 11/28/2025

Page 1 of 4 Policy Number RXMP-24 Line of Business Medicaid & Medicare Effective Date 10/1/2023 (Medicaid), 1/1/2024 (Medicare) Revision Date 12/15/2025

Products: Krystexxa (pegloticase)

Override(s)
Approval Duration
Prior Authorization
Initial: 3 months; COC: up to 9 months (total of 3-9 months per criteria)

HCPCS Description Medical Benefit: Authorization Required; Pharmacy Benefit: Not Covered J2507 Injection, pegloticase (Krystexxa), 1mg

Medicare Criteria
Medicare Part B Coverage Criteria
Review using the most current National Coverage Determination (NCD) then Local Coverage Determination (LCD) that applies to the Hawaii region. The NCD or LCD can be found at: https://www.cms.gov/medicare-coverage- database/search.aspx. • No NCD/ LCD found as of 11/12/2025. Review the criteria below Medicare Part B 90-Day Transition Period For new Medicare members, a 90-day transition period applies. During this time, if a member is currently on an active course of the requested treatment, including when furnished by an out-of-network provider, Coverage and Step Therapy do not apply. After the first 90 days of enrollment, Coverage and Step Therapy Criteria must be met for continued coverage. Medicare Part B Step Therapy Criteria • For new starts, Medicare Part B Step Therapy Criteria must be met in addition to Coverage Criteria before a request may be approved.
• Step therapy: Trial and failure of 2 preferred oral uric acid lowering therapy such as: allopurinol, febuxostat, or probenecid (alone or in combination with allopurinol or febuxostat).

Approval Criteria Products Krystexxa (pegloticase) Line of Business Medicare and Medicaid Approval Length Initial: 3 months Override Type PA, QL Initial Criteria Note: Pharmacy staff: For QUEST non-ABD members with cancer, send ADRC (Aid to Disability Referral Committee) referral with chart notes through G8 CM module.

Criteria:

1. Medication is prescribed or recommended in consultation with a Rheumatologist or Nephrologist; AND
2. Member is 18 years of age or older; AND
3. The requested medication will NOT be used concomitantly with oral urate-lowering therapies; AND
4. One of the following: a. The member has at least 2 flares per year that were inadequately controlled by colchicine or NSAIDs; OR b. The member has at least 1 gout tophus or gouty arthritis AND
5. Member has had an inadequate response to or a clinical reason (see below) for not completing at least a three- month trial at the medically appropriate maximum doses of the following medications: a. Allopurinol or febuxostat b. Probenecid (alone or in combination with allopurinol or febuxostat)

pegloticase (Krystexxa)

Updated on: 11/28/2025

Page 2 of 4 AND

6. The requested medication will be co-administered with weekly oral methotrexate and folic acid or folinic acid supplementation, unless contraindication to or clinical reason to avoid oral methotrexate therapy. AND
7. Lab report within the last 30 days showing that baseline serum uric acid of 6 mg/dL or greater prior to initiating pegloticase; AND
8. The member does not have one or more of the following exclusions for Krystexxa (pegloticase) such as: a. Member has asymptomatic hyperuricemia; b. Member has known hypersensitivity to pegloticase or any of its components; c. Member has a known glucose-6-phosphate dehydrogenase (G6PD) deficiency; or d. Member is using in combination with oral urate-lowering therapy, including but not limited to allopurinol, febuxostat, or probenecid. Renewal Criteria Line of Business Medicare and Medicaid Approval Length COC: up to 9 months (per member demographics) Override Type PA, QL
9. Medication is prescribed or recommended in consultation with a Rheumatologist or Nephrologist; AND
10. The request is for the diagnosis of chronic gout; AND
11. Member is 18 years of age or older; AND
12. The requested medication will NOT be used concomitantly with oral urate-lowering therapies; AND
13. The requested medication will be co-administered with weekly oral methotrexate and folic acid or folinic acid supplementation, unless contraindication to or clinical reason to avoid oral methotrexate therapy;
    AND
14. The member’s last two consecutive uric acid levels are NOT above 6 mg/dL since starting treatment with Krystexxa (pegloticase) or within the last 3 months;
15. AND
16. Member is experiencing benefit from therapy such as: a. Gout flare reduction;
    b. Tophus resolution; or c. Reduction in joint pain. AND
17. For members with no initial tophi, both of the following: a. The member has not received 6-12 months of therapy since the last gout flare-up AND b. Justification as to why the member cannot be uric acid lowering therapy such as: allopurinol, febuxostat, probenecid (alone or in combination with allopurinol or febuxostat), unless contraindicated. NOTE: Prompt replacement of pegloticase with oral uric acid lowering therapy such as: allopurinol, febuxostat, probenecid (alone or in combination with allopurinol or febuxostat) is recommended for those with on therapy for 6-12 months after the last gout flare-up. OR
18. For members with tophi, both of the following: a. Documentation tophus burden have NOT reduced by 90% (from the original); AND b. The member’s functional limitation (such as hand function) was NOT restored NOTE: Oral uric acid lowering therapy such as: allopurinol, febuxostat, probenecid (alone or in combination with allopurinol or febuxostat) should be used once the tophus burden have been reduced by 90% and functional status is restored. Clinical Reasons for not Completing a Three-Month Trial with Allopurinol, Febuxostat, and Probenecid (examples, not all inclusive): • Member experienced a severe allergic reaction to the medication; • Member experienced toxicity with the medication; • Member could not tolerate the medication;

pegloticase (Krystexxa)

Updated on: 11/28/2025

Page 3 of 4 • Member’s current medication regimen has a significant drug interaction; • Member has severe renal dysfunction (allopurinol); • Member has known blood dyscrasias or uric acid kidney stones (probenecid); • Member has renal insufficiency (i.e., glomerular filtration rate 30 mL/minute or less) (probenecid); • Member has end stage renal impairment (febuxostat); • Member has a history of CVD or a new CV event (febuxostat).

Contraindications/Clinical Reasons to Avoid Oral Methotrexate Therapy (examples, not all inclusive) • Clinical diagnosis of alcohol use disorder, alcoholic liver disease, or other chronic liver disease; • Breastfeeding; • Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia); • Elevated liver transaminases; • History of intolerance or adverse event; • Hypersensitivity; • Interstitial pneumonitis or clinically significant pulmonary fibrosis; • Myelodysplasia; • Pregnancy or currently planning pregnancy; • Renal impairment; or • Significant drug interaction

Exclusion

1. Member has asymptomatic hyperuricemia.
2. Member has known hypersensitivity to pegloticase or any of its components.
3. Member has a known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
4. Member is using in combination with oral urate-lowering therapy, including but not limited to allopurinol, febuxostat, or probenecid.

5. For continuation requests, the two most recent serum uric acid levels have been 6 mg/dL or greater.

   FDA Indications & Dosing Indication Dosing/Administration Treatment of chronic gout in adults refractory to conventional therapy. 8 mg IV infusion every 2 weeks as monotherapy (if methotrexate is contraindicated or not clinically appropriate), or coadministered with weekly oral methotrexate and folic acid or folinic acid supplementation; begin methotrexate and folic acid/folinic acid at least 4 weeks prior to starting pegloticase.
   Note: Discontinue pegloticase if pre-infusion serum uric acid levels initially decrease but subsequent preinfusion levels rebound to >6 mg/dL, especially if 2 consecutive levels of >6 mg/dL are observed.

   References

6. DailyMed. Package inserts. U.S. National Library of Medicine, National Institutes of Health website. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Updated periodically.
7. Mandell BF, Yeo AE, Lipsky PE. Tophus resolution in patients with chronic refractory gout who have persistent urate- lowering responses to pegloticase. Arthritis Res Ther. 2018;20(1):286. Published 2018 Dec 29. doi:10.1186/s13075- 018-1782-x
8. Botson JK, Saag K, Peterson J, et al. A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings. Arthritis Rheumatol. 2023;75(2):293-304. doi:10.1002/art.42335
9. Holladay EE, Mudano AS, Xie F, et al. Urate-lowering therapy, serum urate, inflammatory biomarkers, and renal function in patients with gout following pegloticase discontinuation. Arthritis Res Ther. 2024;26(1):86. Published 2024 Apr 12. doi:10.1186/s13075-024-03318-5.

pegloticase (Krystexxa)

Updated on: 11/28/2025

Page 4 of 4

5. Morton AH, Hosey T, LaMoreaux B. Retreatment with Pegloticase after a Gap in Therapy in Patients with Gout: A Report of Four Cases. Rheumatol Ther. 2018;5(2):583-594. doi:10.1007/s40744-018-0111-9

6. Padnick-Silver L, Concoff A, Gao HY, Fu Q, LaMoreaux B, Edwards NL. Oral Urate-Lowering Therapy Use and Efficacy Following Pegloticase Treatment: Findings from a Rheumatology Network Database. Rheumatol Ther. 2025;12(4):709-719.

   Review History 11/25/25: HB Updated to include duration for tophi vs no tophi 12/15/25: YM Updated the initial approval duration