CurrentCentenePolicy CP.PHAR.89

Peginterferon Alfa-2a (Pegasys) Coverage Criteria

Defines medical necessity, coverage criteria, and authorization requirements for peginterferon alfa-2a (Pegasys) across Centene lines of business for specified FDA-approved and NCCN-recommended off-label indications.

Policy Summary

PayerCentene

PolicyPeginterferon Alfa-2a (Pegasys) Coverage Criteria

Policy CodePolicy CP.PHAR.89

Change TypeAnnual review — no material change

Effective Date10.11

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

48 wksApproval duration (CHB)

6 moInitial off-label duration

180 mcgMax weekly dose

Vial/SyringeProduct availability

J3590, S0145HCPCS codes

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Coverage and Indication Criteria

Initial Therapy — NCCN off-label

Covered when ALL of the following are met for NCCN off-label indications

NCCN Off-Label Criteria: 1) Diagnosis is one of: myelofibrosis (low risk and symptomatic), polycythemia vera, essential thrombocythemia, systemic mastocytosis, hairy cell leukemia (single agent), Erdheim-Chester disease, primary cutaneous anaplastic large cell lymphoma (single agent), adult T-cell leukemia/lymphoma (with zidovudine), mycosis fungoides or Seézary syndrome, or chronic myeloid leukemia during pregnancy; 2) Prescribed by or in consultation with an oncologist; 3) For Erdheim-Chester disease, used as a single agent for symptomatic or relapsed/refractory disease; 4) Request meets one of: (a) dose does not exceed 3 mcg/kg per week, or (b) dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.dose <= 3 mcg/kg/week or guideline-supported

Approval duration: 6 months

Initial Therapy — Chronic Hepatitis B

Covered when ALL of the following are met for CHB

CHB Initial Criteria: 1) Diagnosis of chronic hepatitis B virus infection; 2) Prescribed by or in consultation with a gastroenterologist, hepatologist, or infectious disease specialist; 3) Age ≥ 3 years; 4) ONE of: (a) Two elevated ALT lab values within past 12 months (≥ 70 IU/L for men, ≥ 50 IU/L for women) and HBV DNA ≥ 20,000 IU/mL if HBeAg positive or >2,000 IU/mL if HBeAg negative; (b) Diagnosis of cirrhosis, HBV DNA >2,000 IU/mL, and age ≥ 18 years; (c) Liver biopsy showing moderate/severe necroinflammation (Grade 9-18) or significant fibrosis (Stage 2-4); 5) If age ≤ 17 years, member does not have cirrhosis; 6) Dose does not exceed 180 mcg per week.age >= 3; dose <= 180 mcg/week

Approval duration: 48 weeks

Continuation Therapy

Covered when ALL of the following are met for continuation

Continuation Criteria: 1) Member is currently receiving Pegasys via the Centene benefit, or documentation supports member has received Pegasys for a covered indication for at least 30 days; 2) Member is responding positively to therapy; 3) If request is for a dose increase, one of: (a) new dose does not exceed 180 mcg per week; or (b) new dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.>=30 days prior therapy; dose <=180 mcg/week

Approval duration: 12 months (up to 5 years total for melanoma; up to 48 weeks total for HBV)

Requests for indications that are not FDA-approved and are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (see CP.CPA.09, HIM.PA.154, CP.PMN.53) or other evidence of coverage. Other diagnoses for which coverage is not authorized include treatment of chronic hepatitis C (CHC), uncontrolled autoimmune hepatitis, use following heart, lung, or kidney transplant, members with recent drug or alcohol abuse who have not abstained for at least 3 months, and use solely to reduce hepatocellular carcinoma (HCC) risk in members with cirrhosis.

Per the policy update history, osteopenia/osteoporosis has been removed as an off‑label indication because these conditions are recognized as complications of systemic mastocytosis rather than standalone indications for Pegasys.

Interferon‑based regimens, including pegylated interferon therapies, are no longer recommended for the treatment of chronic hepatitis C (CHC) per the 2018 AASLD‑IDSA HCV guidance because safe and effective direct‑acting antiviral agents have superseded interferon‑based therapy. Accordingly, CHC treatment with peg‑interferon is not supported by this policy and approval duration for CHC is not applicable.

Initial Therapy — Approval Conditions

Initial Therapy

Initial approval criteria by indication

NCCN Off-Label Initial: See NCCN-Recommended Off-Label Indications criteria: diagnosis in specified list; oncologist involvement; dosing limits (<=3 mcg/kg/week unless guideline-supported); prescribed regimen must be FDA-approved or NCCN recommended.

CHB Initial: See CHB Initial Criteria: age >=3, specialist involvement, ALT and HBV DNA thresholds or biopsy/cirrhosis criteria, dose <=180 mcg/week.

Approval duration: 48 weeks

INITIAL THERAPY CRITERIA — Approval durations for initial therapy standardized historically for some oncology and off-label uses.

Approval durations for initial therapy standardized historically for some oncology and off-label uses.

Standardized Initial Durations: Policy history standardized initial approval duration for melanoma and NCCN-supported off-label uses to 6 months; continued duration standardized to 12 months in subsequent reviews.

Continuation Therapy — Renewal Conditions

Continuation Therapy — Criteria for continuation of therapy (all indications except CHC)

Criteria for continuation of therapy (all indications except CHC)

Continuation Therapy: 1) Member currently receiving Pegasys via Centene benefit or has received it for at least 30 days; 2) Member is responding positively to therapy; 3) Dose increase requests: new dose must not exceed 180 mcg/week or must be supported by practice guidelines or peer-reviewed literature (prescriber must provide supporting evidence). Prescribed regimen must be FDA-approved or NCCN-recommended.

Approval duration: 12 months (up to 5 years total for melanoma; up to 48 weeks total for HBV)

CONTINUATION CRITERIA — Policy history standardized continued approval durations for certain indications.

Policy history standardized continued approval durations for certain indications.

Standardized Continued Durations: Annual reviews documented standard continued approval durations (example: 12 months continued duration for NCCN-supported off-label uses; special total duration limits for melanoma and HBV noted).

Step and Sequence Requirements

Step	Requirement
CHC preferred regimen	Interferon-based treatment regimens are no longer recommended per 2018 AASLD‑IDSA HCV guidance; prefer direct-acting antivirals (approval duration: Not applicable).

Step	Requirement
Primary cutaneous CD30+ T-cell lymphoproliferative disorder	Clarified as primary cutaneous anaplastic large cell lymphoma and requires use as monotherapy per NCCN (update from 3Q 2025 annual review).

Billing and Coding

Coding — none listedmixed

N/A	No specific CPT/HCPCS/ICD-10 codes listed in this portion of the document

HCPCS Codes referencedHCPCS

J3590	Unclassified biologics
S0145	Injection, pegylated interferon alfa-2a, 180 mcg per mL

HBV DNA and ALT thresholds

ALT thresholdsTwo elevated ALT lab values within the past 12 months: ≥70 IU/L for men or ≥50 IU/L for women.

HBV DNA threshold — HBeAg positiveHBV DNA ≥20,000 IU/mL.

HBV DNA threshold — HBeAg negativeHBV DNA >2,000 IU/mL.

Alternative CHB criteria — cirrhosisDiagnosis of cirrhosis with HBV DNA >2,000 IU/mL and age ≥18 years.

Pegasys maximum dosing for CHB

Maximum weekly dose for adults with CHB180 mcg per week.

Pediatric dosing referencePediatrics: 180 mcg/1.73 m2 × BSA SC per week as monotherapy for 48 weeks (per labeled dosing).

Approval duration associated with CHB dosingApproval duration: 48 weeks when CHB criteria met.

Provider Requirements and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (e.g., office chart notes, lab results, imaging, pathology, or other clinical information) demonstrating that the member meets all applicable approval criteria in this policy. Prescriptions for NCCN-recommended off-label oncology uses must be prescribed by or in consultation with an oncologist.

Applies to all indications listed in the policy
Prescriber specialty requirements noted in criteria must be met

Prior Authorization

Prior Authorization Durations

Approval durations referenced in the policy: initial approval for NCCN-supported off-label oncology indications is 6 months; continued approval for NCCN-supported off-label uses is standardized to 12 months per policy history notes. Chronic hepatitis B approval duration is 48 weeks. Interferon-based regimens for chronic hepatitis C are listed as not applicable.

NCCN-supported off-label initial approval: 6 months
NCCN-supported off-label continued approval: 12 months
Chronic hepatitis B: 48 weeks
Chronic hepatitis C: Not applicable

Denial Risk

Not Authorized Indications

Coverage is NOT authorized for certain diagnoses/indications. Do not submit authorization requests for these unless there is sufficient documentation per applicable off-label policies or evidence-of-coverage allowing coverage.

Non-FDA approved indications not addressed in this policy (unless sufficient documentation per CP.CPA.09, HIM.PA.154, CP.PMN.53 or EOC)
Treatment of chronic hepatitis C (CHC)
Uncontrolled autoimmune hepatitis
Use following heart, lung, or kidney transplants
Members with recent drug or alcohol abuse who have not abstained ≥ 3 months prior to therapy
Sole use to reduce risk of hepatocellular carcinoma (HCC) in cirrhosis

Step Therapy

Step / Sequence and Specialty Updates for Oncology Uses

Step/sequence and specialty requirements for oncology/off-label uses: NCCN-recommended off-label indications require diagnosis-specific criteria, specialist involvement, and dose limits. For certain oncology indications the policy requires monotherapy or combination with specified agents (e.g., adult T-cell leukemia/lymphoma requires combination with zidovudine; primary cutaneous anaplastic large cell lymphoma requires monotherapy). Prescriber must provide supporting evidence if dose exceeds listed limits and regimen must be FDA-approved or NCCN-recommended.

Prescribed by or in consultation with an oncologist for NCCN off-label indications
Hairy cell leukemia and Erdheim-Chester disease included as NCCN-supported off-label uses; hairy cell leukemia requires single agent use per current criteria
Adult T-cell leukemia/lymphoma requires combination with zidovudine
Dose limit for NCCN off-label uses: does not exceed 3 mcg/kg per week unless supported by guidelines or literature with prescriber justification
Prescribed regimen must be FDA-approved or recommended by NCCN

Documentation Required

Required Documentation

Required documentation to support prior authorization: clinical records demonstrating diagnosis, specialty consultation notes, relevant lab results (e.g., HBV DNA, ALT), biopsy/pathology reports when applicable, prior treatment history, and literature or guideline support when dose or indication is off-label. For off-label uses prescriber must submit supporting evidence when dose or regimen deviates from policy criteria.

Office chart notes and specialty consultation
Relevant laboratory results (e.g., HBV DNA, ALT)
Biopsy or pathology reports for liver fibrosis/inflammation or malignancy staging
Supporting peer-reviewed literature or guidelines when requesting dose/regimen outside policy limits

Note

Coverage Decision and Coding Note

Coverage decision documentation note: programmatic and coding changes over time (policy history) may affect approved indications and durations—verify current policy criteria and coding guidance at time of request. Inclusion/exclusion of codes in this policy is informational and does not guarantee coverage.

Policy history includes updates to durations, indications, and dosing limits (see policy history)
Coding listed (e.g., J3590, S0145) is informational only; reference up-to-date coding guidance before claim submission

Background and Drug Information

Peginterferon alfa‑2a (Pegasys) is a pegylated, recombinant interferon alfa‑2a formulation indicated for chronic hepatitis B and historically used for hepatitis C and certain oncology indications. Its pegylation prolongs half‑life to allow weekly dosing. Therapy carries important safety risks; interferon products have boxed warnings and may cause serious neuropsychiatric, autoimmune, ischemic, hematologic, and infectious complications, so specialist oversight and appropriate monitoring are required.

Key Terms and Safety

Key terms and safety

Key abbreviationsCHB = chronic hepatitis B; CHC = chronic hepatitis C.

Boxed warning summaryMay cause or aggravate fatal or life‑threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.

Contraindications (selected)Autoimmune hepatitis; hepatic decompensation (Child‑Pugh score > 6, class B and C); hypersensitivity; neonates/infants.

AASLD CHC guidanceAs of 2018, AASLD/IDSA guidelines do not recommend PEG‑interferon for CHC; use direct‑acting antivirals instead.

Definition updated per 2024 WHO CHB guidelines

Definition change — significant fibrosisUpdated from stage 3–4 to stage 2–4 per 2024 WHO CHB guidelines.

Source of update3Q 2024 annual review referenced WHO 2024 CHB guideline change.

Effective documentationPolicy references updated definition in annual review notes (Date = 05.21.24; P&T Approval Date = 08.24).

Quantity and Dosing Limits

Peginterferon alfa-2a (Pegasys)

Drug name and formulationPeginterferon alfa-2a (Pegasys) — covalent conjugate of recombinant alfa‑2a interferon; available as 180 mcg/mL vial and 180 mcg/0.5 mL prefilled syringe.

Standard adult SC dose for CHB180 mcg SC per week as monotherapy for 48 weeks.

Product availabilityVial: 180 mcg/mL; Prefilled syringe: 180 mcg/0.5 mL (4 syringes/pack).

Administration routeSubcutaneous (SC) per labeled dosing.

Administration Site and Setting