ModifiedPremera BluecrossPolicy 5.01.616

Pharmacologic Treatment of Gout

Criteria for medical and pharmacy benefit review of drugs used to treat gout, including site-of-service medical necessity for certain IV/injectable agents; affects providers prescribing/administering listed gout therapies for Premera Blue Cross members.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Gout

Policy CodePolicy 5.01.616

Change TypeModified — material updates to Krystexxa co-administration and added Ilaris criteria

Effective DateMar. 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and document co-administration of Krystexxa with oral methotrexate 15 mg weekly unless contraindicated.

SourceLink

POLICY UPDATE CHANGES

Requirement that Krystexxa is co-administered with oral methotrexate 15 mg weekly unless methotrexate is contraindicated or not clinically appropriate.

Added coverage criteria for Ilaris (canakinumab) for the treatment of acute gout flares.

Moved multiple gout drug brands from Policy 5.01.605 to Policy 5.01.616 without changes to coverage criteria.

Non-formulary exception review authorizations for all drugs listed may be approved up to 12 months.

Removed coverage criteria for Mitigare (colchicine).

Added Colcrys (colchicine) to list of gout drugs that require prior trial of generic oral colchicine or generic oral allopurinol with inadequate response.

Added site of service review to Ilaris (canakinumab) and clarified Site of Service Medical Necessity criteria can apply to injection drugs.

2drugs with age-based medical necessity statements

150 mg q12w

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Coverage Criteria for Gout Therapies

inv-01: Ilaris (canakinumab) - Acute Gout

Covered when ALL of the following are met for Ilaris (canakinumab) for acute gout flares:

Ilaris acute gout criteria: Member is aged 18 years or older; has intolerance, contraindication, or lack of response to NSAIDs and colchicine for acute gout flares; has been previously treated with oral or injectable corticosteroids and is unable to be retreated with a repeat course of corticosteroids; Ilaris will be used in combination with a urate-lowering medication unless contraindicated; dose limited to 150 mg every 12 weeks; prescribed by or in consultation with a rheumatologist.

Supported by randomized trials demonstrating pain reduction at 72 hours in individuals unable to use NSAIDs/colchicine.

inv-02: Krystexxa (pegloticase) - Chronic Gout

Covered when ALL of the following are met for Krystexxa (pegloticase) for chronic gout:

Krystexxa initial criteria: Member is aged 18 years or older; tried allopurinol with documentation of one of the following: inadequate response after ≥3 months at maximum tolerated dose with serum uric acid remaining >6 mg/dL, OR intolerance to allopurinol, OR contraindication to allopurinol or positive HLA-B*5801; has tried febuxostat or probenecid unless clinically inappropriate and serum uric acid remains >6 mg/dL; documentation of no G6PD deficiency; Krystexxa administered as an 8 mg infusion every 2 weeks; co-administered with oral methotrexate 15 mg weekly unless methotrexate is contraindicated or not clinically appropriate; prescribed by or in consultation with a rheumatologist.sUA > 6 mg/dL for inadequate response

Methotrexate co-administration requirement added based on randomized trial evidence showing improved Month 6/12 responder rates.

inv-03: Krystexxa (pegloticase) coverage criteria

Covered when ALL of the following are met

Krystexxa initial coverage: Individual has chronic gout refractory to conventional therapy with baseline serum uric acid ≥7 mg/dL (trial entry threshold) and inability to maintain serum uric acid <6 mg/dL or intolerance to urate-lowering therapy; Krystexxa is co-administered with oral methotrexate 15 mg weekly unless methotrexate is contraindicated or not clinically appropriate; individuals receive standardized infusion reaction prophylaxis and gout flare prophylaxis; prescriber documents prior trials, G6PD status, and clinical rationale; therapy prescribed by or in consultation with a rheumatologist.achieve and maintain sUA <6 mg/dL for ≥80% of the time during the designated month

Randomized trial (NCT03994731) required methotrexate run-in and demonstrated improved Month 6 and Month 12 responder rates with methotrexate co-administration.

inv-04: Ilaris (canakinumab) coverage criteria

Covered when ALL of the following are met

Ilaris coverage for acute gout flare: Individual has an acute gout flare and is unable to use or has contraindication/intolerance to NSAIDs and/or colchicine, with history of ≥3 gout flares in the previous year; has been previously treated with oral or injectable corticosteroids and is unable to be retreated with a repeat course of corticosteroids; Ilaris will be used in combination with a urate-lowering medication unless contraindicated; dose limited to 150 mg every 12 weeks; medication prescribed by or in consultation with a rheumatologist; site-of-service review may apply.pain reduction at 72 hours observed in trials

Efficacy supported by two 12-week randomized studies and extensions.

All uses of the medications listed in this policy that are not explicitly described in the coverage criteria are considered investigational and are not covered.

Coverage criteria for Mitigare (colchicine) have been removed from this policy; as of the latest update, Mitigare is no longer covered under this policy.

Requests for infusion or injectable therapy provided in sites that do not meet the policy’s Site of Service medical necessity criteria (for example, hospital outpatient infusion when criteria are not met) are considered not medically necessary and may be denied.

An every-4-week dosing regimen of Krystexxa demonstrated a higher frequency of anaphylaxis and infusion reactions and was less effective for tophus resolution compared with the every-2-week regimen; therefore the 4-week schedule is not favored by the policy.

Billing and Coding

HCPCS CodesHCPCS

J0638	Injection, canakinumab (Ilaris), 1 mg
J2507	Injection, pegloticase (Krystexxa), 1 mg

Covered HCPCS CodesHCPCSCovered

J2507	Krystexxa (pegloticase) injection
J0638	Canakinumab (Ilaris) injection

inv-11: Serum uric acid (sUA) — target value

Target serum uric acid (sUA)Maintain sUA < 6 mg/dL

Evidence use for re-authorizationDocumented sUA < 6 mg/dL demonstrates continued positive clinical response

Approval length tied to responseNon-formulary and other reviews may be approved up to 12 months if sUA < 6 mg/dL is documented

inv-12: Trial entry sUA — >= threshold

Trial entry sUA threshold>= 7 mg/dL

Context in trial eligibilityBaseline sUA >=7 mg/dL required for Krystexxa + methotrexate randomized trial (individuals unable to maintain sUA <6 mg/dL)

Provider Requirements and Actions

Prior Authorization

Prior Authorization Required

Prior authorization is required for select HCPCS codes and certain agents listed in this policy. Requests for Krystexxa (pegloticase) and Ilaris (canakinumab) — HCPCS J2507 and J0638 — are subject to prior authorization and site-of-service review where applicable.

HCPCS J2507 (Krystexxa) — prior auth required
HCPCS J0638 (Ilaris) — prior auth required

Documentation Required

Required Chart Documentation

Submit medical record documentation to support medical necessity at the time of prior authorization request. Include office visit notes documenting the diagnosis, relevant history, physical exam, medication history, and G6PD status (when relevant). Chart notes should demonstrate treatment history, response to prior therapies, and any contraindications or intolerance that justify use of the requested agent.

Office visit notes with diagnosis, relevant history, physical evaluation

Background and Scope

Gout is an inflammatory arthritis caused by deposition of monosodium urate crystals in joints and soft tissues due to sustained hyperuricemia. Chronic gout is characterized by recurrent acute flares, risk of tophi formation, and potential complications such as kidney stones and joint damage. Persistent elevations in serum uric acid promote crystal formation; levels above approximately 6.8 mg/dL increase the risk of monosodium urate crystal deposition. Management of chronic gout focuses on urate-lowering strategies to prevent flares and resolve tophi over time.

Key Definitions

inv-23: Chronic gout defined as two or more gout attacks in a year

DefinitionChronic gout is defined as two or more gout attacks in a year.

Clinical significanceUsed to identify individuals for long-term urate-lowering therapy consideration

Policy useReferenced in coverage rationale and background to define chronic disease state

inv-24: Serum uric acid threshold — >6.8 mg/dL predisposes to crystal formation

Crystal formation threshold> 6.8 mg/dL predisposes to monosodium urate crystal formation

Mechanism noteHigher sUA increases supersaturation and nucleation leading to crystal growth

Initial Therapy Criteria

inv-26: Krystexxa Initial Therapy

Initial authorization criteria for Krystexxa:

Krystexxa initial therapy: Individual is aged ≥18 years; documented trial of allopurinol with either inadequate response after ≥3 months at maximum tolerated dose (sUA >6 mg/dL) OR intolerance/contraindication to allopurinol (including HLA-B*5801 positive where applicable); trial of febuxostat or probenecid unless clinically inappropriate with persistent sUA >6 mg/dL; documentation of no G6PD deficiency; initiate oral methotrexate 15 mg weekly and tolerate for at least 2 weeks prior to first Krystexxa infusion when not contraindicated; Krystexxa dosing 8 mg IV every 2 weeks; standardized infusion reaction prophylaxis and gout flare prophylaxis provided; prescribed by or in consultation with a rheumatologist.baseline sUA ≥7 mg/dL in trial populations; inadequate response defined as sUA >6 mg/dL

Methotrexate co-administration requirement added in 2022 to reduce anti-drug antibody formation and improve efficacy.

inv-27: Krystexxa initial therapy

Initial therapy requirements (supporting methotrexate co-administration requirement):

Continuation and Re-authorization Criteria

inv-28: Re-authorization

Re-authorization requirements

Re-authorization general: Re-authorization (including non-formulary exception reviews) may be approved up to 12 months provided drug-specific coverage criteria are met and chart notes document continued positive clinical response such as a documented serum uric acid level less than 6 mg/dL.sUA < 6 mg/dL

Approval length and re-authorization guidance applied to Ilaris and Krystexxa per policy.

inv-29: Krystexxa continuation

Continuation/maintenance considerations and responder thresholds for Krystexxa:

Continuation of Krystexxa: Continued therapy is supported when the individual demonstrates maintained serum uric acid <6 mg/dL (defined in trials as <6 mg/dL for ≥80% of the time during the designated month) and tolerability; continue weekly methotrexate as tolerated to reduce anti-drug antibody formation; monitor for infusion reactions and hemolysis in individuals with G6PD deficiency; prescriber documents clinical response and monitoring.

Step Therapy Requirements

Requirement	Drugs to which this applies	Failure definition / Next step
Trial of generic oral colchicine or generic oral allopurinol is required prior to approval of brand colchicine or brand urate-lowering agents.	Brand colchicine (e.g., Colcrys), Gloperba, Uloric (febuxostat), Zyloprim (allopurinol) and other branded urate‑lowering/colchicine products moved into this policy.	Documented inadequate response to an adequate trial of generic oral colchicine or generic oral allopurinol; if inadequate response, proceed to consider brand therapy with supporting documentation.

Step requirement	Examples (branded agents)	Exception / Documentation
Member must have tried generic oral colchicine or generic oral allopurinol and had an inadequate response before approval of certain branded gout drugs.	Colcrys (brand colchicine) and other branded colchicine formulations requiring step therapy per policy (brands added to this policy Oct 3, 2025).	If generic trial is contraindicated or not tolerated, document contraindication/intolerance in chart notes to support approval of the branded agent.

Site of Service Medical Necessity

Note

Site-of-Service review applies; preferred medically necessary sites listed

Site of Service medical necessity review applies to IV and injectable drugs; medically necessary sites include physician office, infusion center, home infusion, and, in specified circumstances, hospital outpatient settings.

Site-of-service defined as hospital-based outpatient, infusion center, physician's office, or home.
Hospital outpatient setting is medically necessary for the initial 90 days for initial course or when specific clinical risk factors or lack of local alternatives exist.

Note

Site-of-service review may be required for Ilaris (canakinumab)

Site-of-service review may be applied to Ilaris (canakinumab); requests for administration in non-preferred sites may trigger a site-of-service medical necessity review and possible denial if criteria are not met.

Ilaris is specifically listed as subject to site-of-service review.
Policy clarifies Site of Service Medical Necessity criteria can apply to injection drugs.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Gout

Policy CodePolicy 5.01.616

Change TypeModified — material updates to Krystexxa co-administration and added Ilaris criteria

Effective DateMar. 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and document co-administration of Krystexxa with oral methotrexate 15 mg weekly unless contraindicated.

SourceLink

On This Page

inv-13: Serum uric acid (sUA) response threshold — achieve and maintain <6 mg/dL for at least 80% of time during designated month

Responder definition (month-specific)Achieve and maintain serum/plasma uric acid <6 mg/dL for at least 80% of the time during the designated month

Primary endpoint timing (Krystexxa trials)Month 6 responder was primary endpoint in the methotrexate co‑administration trial; Month 3/6 used in other Krystexxa trials

Responder used for re-authorization/continuationContinued benefit associated with maintained sUA <6 mg/dL (>=80% of time during month) per continuation criteria

Documentation Required

Required Documentation and History

Include supporting policy history and rationale in the submission when applicable. Examples: documentation that Krystexxa will be co‑administered with oral methotrexate 15 mg weekly (or a clinical reason why methotrexate is contraindicated), records showing prior trials of allopurinol/febuxostat/probenecid with serum uric acid levels, and dates of provider notification or consultations (e.g., rheumatology). Failure to provide these items may result in denial or delay.

Evidence Krystexxa is co‑administered with oral methotrexate 15 mg weekly or contraindication to methotrexate
Prior trial documentation for allopurinol (including maximum tolerated dose and 3‑month trial) and other urate‑lowering therapies with serum uric acid results
Provider consultation or prescribing rheumatologist documentation and consultation dates
Site‑of‑service review notes when applicable

Step Therapy

Generic Trial Requirement

A trial of generic oral colchicine or generic oral allopurinol is required before coverage of certain branded agents. The record must show an inadequate response to these generics unless there is a documented intolerance or contraindication.

Trial of generic oral colchicine required prior to branded colchicine products (Colcrys, Gloperba) unless contraindicated
Trial of generic oral allopurinol required prior to branded urate‑lowering agents unless contraindicated

Step Therapy

Step Requirement for Branded Colchicine/Allopurinol

Branded colchicine and branded allopurinol/urate lowering agents require step or trial of generic alternatives first. Requests for brand agents (e.g., Colcrys, Gloperba, Uloric, Zyloprim) should include documentation of the generic trial and outcome; exceptions for intolerance or contraindication must be clearly documented.

Branded colchicine (Colcrys, Gloperba) — document trial and inadequate response to generic colchicine or contraindication
Branded allopurinol (Zyloprim) and febuxostat (Uloric) — document trial and inadequate response to generic allopurinol or contraindication