Notification

Pegloticase (Krystexxa®)


Notification Issue Date: 10/15/2019

This version of the policy will become effective 01/13/2020.

The following new policy has been updated to communicate the Dosing and Frequency requirements for pegloticase (Krystexxa®).



Medicare Advantage Policy

Title:Pegloticase (Krystexxa®)
Policy #:MA08.060d

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Pegloticase (Krystexxa®) is considered medically necessary and, therefore, covered for the treatment of symptomatic chronic gout in adult individuals when all of the following criteria, including Dosing and Frequency Requirements, are met:
  • Failure to normalize uric acid levels to less than 6 mg/dL after at least three months of one xanthine oxidase inhibitor (eg, allopurinol or febuxostat) at the maximum recommended dose, unless the individual is intolerant to, has had a toxic reaction to, or has a contraindication to taking xanthine oxidase inhibitors.
  • Individual has at least one of the following:
    • at least three gout flares in the previous 18 months
    • at least one gout tophus
    • gouty arthritis
  • Dosing and Frequency: 8 mg IV infusion every two weeks

DOSING AND FREQUENCY REQUIREMENTS

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of pegloticase (Krystexxa®). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of pegloticase (Krystexxa®) outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the utilization management activities. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for pegloticase (Krystexxa®).

EXPERIMENTAL INVESTIGATIONAL

The use of pegloticase (Krystexxa®) for non-adults or for individuals with asymptomatic hyperuricemia, is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this use cannot be established by review of the available published peer-reviewed literature.

All other uses for pegloticase (Krystexxa®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of pegloticase (Krystexxa®) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.
Policy Guidelines

There is no Medicare coverage determination addressing pegloticase (Krystexxa®); therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, pegloticase (Krystexxa®) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria and Dosing and Frequency Requirements listed in this medical policy are met.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when pegloticase (Krystexxa®) is covered under a member's medical benefit (Part B benefit). It does not address instances when pegloticase (Krystexxa®) is covered under a member’s pharmacy benefit (Part D benefit).

DRUG ADMINISTRATION

Pegloticase (Krystexxa®) is administered by intravenous infusion; it should not be given as a push or bolus. Pegloticase (Krystexxa®) is not recommended for the treatment of asymptomatic hyperuricemia.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

U.S. FOOD AND DRUG ADMINISTRATION (FDA)

Pegloticase (Krystexxa®) was approved by the FDA on September 14, 2010, for treatment of individuals with chronic gout that is refractory to conventional therapy.

PEDIATRIC USE

The safety and effectiveness of pegloticase (Krystexxa®) in pediatric individuals have not been established.

Description

Pegloticase (Krystexxa®) is an intravenously administered uric acid--specific enzyme. It is a recombinant uricase (PEGylated) indicated for the treatment of symptomatic chronic gout in adults (18 years and older) who are refractory to the conventional therapy of xanthine oxidase inhibitors (eg, allopurinol [Zyloprim] or febuxostat [Uloric™]) at the maximum recommended dose, unless intolerant, toxic, or contraindicated. Pegloticase (Krystexxa®) achieves its therapeutic effect by increasing the conversion of uric acid to allantoin, which lowers the serum uric acid level. The allantoin is then excreted by the kidneys.

BACKGROUND OF GOUT

Gout (monosodium urate crystal deposition disease) is a form of arthritis caused by a buildup of plasma uric acid (a by-product of protein metabolism). This uric acid buildup is known as hyperuricemia. There are two categories of hyperuricemia:
  • Primary hyperuricemia: lasts indefinitely and occurs in the absence of comorbidities or drugs that alter uric acid production or its excretion.
  • Secondary hyperuricemia: excessive urate production or decreased renal function resulting from disease, diet, drug, or toxin.

Individuals diagnosed with gout have usually had hyperuricemia for a considerable amount of time. Many individuals with hyperuricemia have no symptoms (asymptomatic hyperuricemia) for years. Gout manifests acutely with pain, inflammation, swelling, and, possibly, cellulitis. The knees and feet are usual sites of gout flares, but any joint is susceptible. Severe gout flares in the joints of the foot, especially the great toe, are referred to as podagra.

There are four stages of gout:
  • Asymptomatic phase: individual has no overt symptoms of gout but does have hyperuricemia and crystalline deposits into tissues.
  • Acute gouty arthritis: occurs after years of asymptomatic hyperuricemia.
  • Intercritical (interval) gout: there is a gap between flares, but individual is otherwise symptom free and has no joint problems.
  • Chronic recurrent and tophaceous (nodules composed of uric acid) gout: after many years of flares, this stage is disabling and involves permanent damage to joints and kidneys.

Gout may manifest as one or more of the following:
  • Recurrent acute inflammatory arthritis flares
  • Chronic arthropathy
  • Formation of tophaceous deposits (urate crystals)
  • Uric acid nephrolithiasis
  • Chronic nephropathy (due to comorbid states)

Acute gout flares may be treated with dietary changes (eg, decreasing/abstinence from consumption of alcohol, fructose-sweetened drinks, meat, and seafood), non-steroidal anti-inflammatory drugs (NSAID), steroids and colchicine (Colcrys®). Chronic gout treatment usually includes antihyperuricemia medications.

PEER-REVIEWED LITERATURE

SUMMARY
The safety and effectiveness of pegloticase (Krystexxa®) was demonstrated in two replicate, multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint of both studies was the achievement of a plasma uric level of less than 6 mg/dL. Both studies reported a statistically significant lowering of the plasma uric levels (under 6 mg/dL) in those receiving pegloticase (Krystexxa®), compared to those receiving placebo.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References

American Hospital Formulary Service (AHFS). Pegloticase (Krystexxa®). Lexicomp Drug Information 2019. [Lexicomp Online Web site]. 12/2014. Available at:
http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 27, 2019.

Becker MA, Mount DB. Asymptomatic hyperuricemia. 02/06/19. [UpToDate Web Site]. Available at: http://www.uptodate.com/contents/asymptomatic-hyperuricemia?source=search_result&search=Secondary+hyperuricemia&selectedTitle=1%7E150 . Accessed August 27, 2019.

Becker MA, Gaffo AL. Clinical manifestations and diagnosis of gout. 03/06/19. [UpToDate Web site]. Available at: http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-gout?source=machineLearning&search=Clinical+manifestations+and+diagnosis+of+gout&selectedTitle=1%7E150&sectionRank=1&anchor=H111564623#H111564623 [via subscription only]. Accessed August 27, 2019.

Centers for Disease Control and Prevention. Gout. [CDC Website]. Last reviewed 01/28/19. Available at: http://www.cdc.gov/arthritis/basics/gout.htm. Accessed August 27, 2019.

Elsevier’s Clinical Pharmacology Compendium. Pegloticase (Krystexxa®). 07/19/19. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed August 27, 2019.

Lexi-Drugs Compendium. Pegloticase (Krystexxa®). 08/21/19. [Lexicomp Online Web site]. Available at:
http://online.lexi.com/lco/action/home . [via subscription only]. Accessed August 27, 2019.

Pegloticase (Krystexxa®). [prescribing information] Lake Forest, WI: Horizon Pharma; 07/2018. Available at: http://www.krystexxa.com/ . Accessed August 27, 2019.

Sriranganathan MK, Vinik O, Bombardier C, Edwards CJ. Interventions for tophi in gout. Cochrane Database Syst Rev. 2014 Oct 20;10:CD010069.

Sundy J, Ganson N, Kelly S, et al. Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinent mammalian urate oxidase in patients with refractory gout. Arthritis Rheum. 2007;56(4):1370.

Sundy J, Becker M, Baraf H, et al. Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: results of a phase II randomized study. Arthritis Rheum. 2008;58(9):2882-2891.

Truven Health Analytics Inc. Micromedex® Solutions. Pegloticase (Krystexxa®). [Micromedex® Web site]. 08/26/18. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/ [via subscription only]. Accessed August 27, 2019.

US Food and Drug Administration (FDA). Center for Drug evaluation and Research. Drugs @FDA. Pegloticase (Krystexxa®) [FDA Website]. 07/2018. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 27, 2019.


Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment A


HCPCS Level II Code Number(s)

J2507 Injection, pegloticase, 1 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Pegloticase (Krystexxa®)
Description: ICD-10 Codes and Narratives






Policy History

MA08.060d
01/13/2020The following new policy has been updated to communicate the Dosing and Frequency requirements for pegloticase (Krystexxa®).

MA08.060c
01/01/2019This policy was updated to communicate the Company's coverage position for pegloticase (Krystexxa®).

MA08.060b
04/20/2016This policy has been updated to convey the FDA package insert regarding the lack of studies in the pediatric population.

MA08.060a
01/15/2015This policy has been updated to include a clinical trial summary and information about potential off-label indications.

MA08.060
01/01/2015This is a new policy.




Version Effective Date: 01/13/2020
Version Issued Date: 01/13/2020
Version Reissued Date: N/A