CurrentAnthemPolicy CC-0057

Krystexxa (pegloticase) Clinical Criteria

Defines medical necessity criteria, continuation and exclusion criteria, quantity limits, coding, and administration requirements for Krystexxa (pegloticase) under the medical benefit.

Policy Summary

PayerAnthem

PolicyKrystexxa (pegloticase) Clinical Criteria

Policy CodePolicy CC-0057

Change TypeQuantity limit; methotrexate coadministration requirement

Effective DateJul 23, 2025

Next Review Date

Key ActionWhen seeking prior authorization, document age (>=18), chronic gout diagnostic features, baseline serum uric acid >=6 mg/dL, failure/intolerance/contraindication to specified conventional therapies, and a plan to coadminister methotrexate plus folic/folinic acid unless contraindicated.

SourceLink

POLICY UPDATE CHANGES

04/01/2024 - Add quantity limit.

05/19/2023 - Add criteria for combination use with methotrexate; add may not approve criteria for combination use with oral urate-lowering therapy and for repeated elevated serum uric acid levels.

06/09/2025 - Annual Review: No changes. Coding Reviewed: No changes.

2Vial limit per 28 days

>=18Minimum age (years)

>=6Baseline serum uric acid threshold (mg/dL)

Consecutive elevated SUA levels that may prompt discontinuation

Coverage Summary

Coverage stance: covered_with_criteria. Scope: This policy defines medical necessity criteria, continuation and exclusion criteria, quantity limits, coding, and administration requirements for Krystexxa (pegloticase) under the medical benefit. Subject: Krystexxa (pegloticase). Status: CURRENT.

Summary: Initial and continuation use may be approved only when specific clinical criteria are met (for example, adult patients with chronic refractory gout as defined by recurrent flares, tophi, or gouty arthropathy, baseline serum uric acid ≥ 6 mg/dL, prior failure/intolerance/contraindication to conventional therapies, and a plan to coadminister methotrexate with folic/folinic acid unless contraindicated). A quantity limit of 2 vials per 28 days is applied.

Key thresholds and limits for Krystexxa (pegloticase)

Baseline serum uric acid>= 6 mg/dL

Continuation serum uric acid requirementRecent two levels < 6 mg/dL required; two most recent >= 6 mg/dL may prompt discontinuation/denial

Minimum age>= 18 years

Vial limit per 28 days2 vials per 28 days

Initial Therapy Criteria (Approval)

Initial therapy (Approval criteria)

Initial requests for Krystexxa (pegloticase) may be approved if ALL of the following are met:

ALL of the following

Age: Individual is 18 years of age or older>=18
Chronic gout diagnosis
- ONE of
  - Three or more gout flares in the previous 18 months
  - One or more tophus present

Continuation Therapy Criteria (Renewal)

Continuation therapy (Renewal criteria)

Continuation requests for Krystexxa (pegloticase) may be approved if ALL of the following are met:

ALL of the following

Clinical improvement: There is clinically significant improvement in clinical signs and symptoms of disease (including but not limited to reduction in serum uric acid level, gout flare reduction, tophus resolution, reduction in joint pain)
Examples listed as provided in source
Methotrexate coadministration: Krystexxa will be administered in combination with methotrexate and folic acid/folinic acid supplementation unless contraindicated or not clinically appropriate
Methotrexate coadministration required unless contraindicated

ref

Not Approved / Exclusions

Not approved (Exclusions)

Krystexxa (pegloticase) may not be approved when ANY of the following are present:

ANY of the following

Asymptomatic hyperuricemia: Individual has asymptomatic hyperuricemia
G6PD deficiency: Individual has a known glucose-6-phosphate dehydrogenase (G6PD) deficiency
Do not administer to individuals with G6PD deficiency (risk of hemolysis and methemoglobinemia)
Concurrent oral ULT: Individual is using in combination with oral urate-lowering therapy (including but not limited to allopurinol, febuxostat, probenecid)
Concurrent oral ULT prohibited

Applicable Codes

HCPCS - Drug administration code for KrystexxaHCPCSCovered

J2507

Injection, pegloticase, 1mg [Krystexxa]

ICD-10 Diagnosis codes (informational)ICD-10

M1A.00X0-M1A.9XX1	Chronic gout
M10.00-M10.9	Gout

Billing Rule

Quantity limit

Limit = 2 vials per 28 days for Krystexxa (8 mg/mL single dose vial).

J2507

Provider Actions & Documentation Requirements

Prior Authorization

Prior authorization required with documented criteria

Submission must include documentation of age >=18; chronic gout diagnostic features (three or more gout flares in the previous 18 months OR one or more tophus OR history of gouty arthropathy); baseline serum uric acid >=6 mg/dL prior to initiation; failure, intolerance, or contraindication to specified conventional therapies; and a plan for methotrexate plus folic/folinic acid coadministration unless contraindicated.

J2507

Documentation Required

Monitoring & screening

Baseline serum uric acid prior to initiation
Monitor serum uric acid prior to infusions

Clinical Evidence & Guidelines

Evidence: Pivotal trials — Sundy et al. 2011 randomized trials support the efficacy and tolerability of pegloticase in patients with chronic gout refractory to conventional treatment. Guideline: The 2020 ACR gout guideline (FitzGerald 2020) is referenced for therapy sequencing and serum urate targets, including recommending xanthine oxidase inhibitors as first-line ULT and targeting serum urate < 6 mg/dL.

Background & Definitions

Krystexxa (pegloticase) is a recombinant uricase approved for adults with chronic gout refractory to conventional therapy. The policy defines chronic refractory gout consistent with the trials as three or more gout flares in 18 months, one or more tophi, or gouty arthropathy. Krystexxa carries black box warnings for anaphylaxis and infusion reactions and for hemolysis/methemoglobinemia in individuals with G6PD deficiency; individuals should be screened for G6PD deficiency and Krystexxa should not be administered to those with known G6PD deficiency.

Methotrexate coadministration reduces anti-drug antibody incidence and titers, allowing increased Krystexxa exposure, and the policy specifies Krystexxa should be coadministered with weekly methotrexate plus folic/folinic acid unless contraindicated or not clinically appropriate.

Term	Definition
Chronic refractory gout (trial definition)
Three or more self-reported gout flares during the previous 18 months, one or more tophi, or gouty arthropathy with joint damage due to gout.
G6PD deficiency
Glucose-6-phosphate dehydrogenase deficiency; contraindication to Krystexxa due to risk of hemolysis and methemoglobinemia.

Revision History

04/01/2024material

04/01/2024 - Add quantity limit. Krystexxa (pegloticase) 8 mg/mL single dose vial limit = 2 vials per 28 days.

05/19/2023material

05/19/2023 - Add criteria for combination use with methotrexate (requirement that Krystexxa be administered in combination with methotrexate and folic/folinic acid unless contraindicated); clarify may not approve when used in combination with oral urate-lowering therapy; add continuation denial criteria for repeated elevated serum uric acid levels (two most recent SUA levels ≥ 6 mg/dL).

06/09/2025non-materialLatest

Policy Summary

PayerAnthem

PolicyKrystexxa (pegloticase) Clinical Criteria

Policy CodePolicy CC-0057

Change TypeQuantity limit; methotrexate coadministration requirement

Effective DateJul 23, 2025

Next Review Date

SourceLink

On This Page

History of chronic gouty arthropathy, defined clinically or radiographically as joint damage due to gout

Baseline SUA: Documentation is provided that individual has a baseline serum uric acid of 6 mg/dL or greater prior to initiating Krystexxa (pegloticase)>=6 mg/dL

Prior conventional therapy

Options
- A xanthine oxidase inhibitor (allopurinol or febuxostat)
- Combination therapy of 1 xanthine oxidase inhibitor given with a uricosuric agent (for example, probenecid)

Methotrexate coadministration: Krystexxa will be administered in combination with methotrexate and folic acid/folinic acid supplementation unless contraindicated or not clinically appropriate

Methotrexate coadministration required unless contraindicated

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Prior Authorization

Prior authorization required with documented criteria

Prior authorization requires documentation of: age >=18; chronic gout diagnostic features (three or more gout flares in the previous 18 months OR one or more tophus OR history of chronic gouty arthropathy); baseline serum uric acid >=6 mg/dL prior to initiating therapy; failure, intolerance, or medical contraindication to specified conventional therapies (e.g., xanthine oxidase inhibitor such as allopurinol or febuxostat, or combination therapy with a uricosuric); and a documented plan to administer Krystexxa in combination with methotrexate plus folic acid/folinic acid supplementation unless contraindicated.

J2507

Documentation Required

Co-administration with methotrexate

Coadministration of weekly methotrexate with folic acid or folinic acid supplementation is required for approval unless contraindicated or not clinically appropriate. Document the plan for methotrexate plus folic/folinic acid when submitting requests.

Unless contraindicated or not clinically appropriate

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Documentation Required

Baseline and ongoing serum uric acid monitoring

Provide a baseline serum uric acid (SUA) measurement prior to initiating Krystexxa and monitor SUA prior to each infusion. Two consecutive SUA levels of 6 mg/dL or greater are grounds to consider discontinuation and may lead to denial for continuation.

Documentation Required

Co-administration with methotrexate required for continuation

For continuation, document the plan to coadminister methotrexate with folic acid/folinic acid supplementation; coadministration is required unless contraindicated or not clinically appropriate.

Continuation SUA elevations: For continuation requests, the two most recent serum uric acid levels have been 6 mg/dL or greater>=6 mg/dL (two most recent)

Two consecutive elevated SUA levels may prompt discontinuation/denial

Other indications not met: May not be approved when the above criteria are not met and for all other indications

Documentation Required

G6PD screening

Screen individuals at risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to initiating Krystexxa. Do not administer Krystexxa to individuals with a known G6PD deficiency due to risk of hemolysis and methemoglobinemia.

Denial Risk

Continuation denial risk for elevated serum uric acid and prohibition with oral ULT

Continuation may be denied if the two most recent serum uric acid levels are 6 mg/dL or greater. Use of Krystexxa in combination with oral urate-lowering therapy (for example allopurinol, febuxostat, probenecid) is prohibited and may result in denial.

Screen for G6PD deficiency prior to starting Krystexxa

Discontinue/deny continuation if two consecutive serum uric acid levels are >= 6 mg/dL

Background note: Methotrexate coadministration reduces anti-drug antibody incidence and titers and is recommended; the policy requires Krystexxa to be administered with methotrexate and folic/folinic acid supplementation unless contraindicated.

06/09/2025 - Annual Review: No changes. Coding Reviewed: No changes.