CurrentCentenePolicy CP PHAR.89

Clinical Policy: Peginterferon Alfa-2a (Pegasys)

Defines Centene medical necessity and authorization criteria for peginterferon alfa-2a (Pegasys) across commercial, HIM, and Medicaid lines of business, including FDA-approved and selected NCCN-recommended off-label oncology uses, CHB, and exclusions (partial document).

Policy Summary

PayerCentene

PolicyPeginterferon Alfa-2a (Pegasys) coverage criteria

Policy CodePolicy CP PHAR.89

Change TypeRoutine review — no material changes

Effective DateOct 11, 2023

Next Review DateAug 25, 2025

Key ActionSubmit prior authorization with documentation showing member meets approval criteria (diagnosis, specialist prescriber/consult, labs or biopsy, and dose ≤180 mcg/week).

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

48CHB approval (weeks)

6 monthsInitial off-label oncology

180 mcgMax dose/week

Syringe, vialFormulations

J3590, S0145HCPCS codes

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Coverage Criteria

Initial Approval — NCCN-Recommended Off-Label Oncology Indications

Covered when ALL required conditions are met for NCCN‑recommended off‑label oncology uses.

Initial oncology criteria: 1) Diagnosis is one of the following NCCN‑recommended off‑label hematologic/oncologic conditions: polycythemia vera; low‑risk symptomatic myelofibrosis; essential thrombocythemia; hairy cell leukemia (when prescribed as a single agent); systemic mastocytosis; Erdheim‑Chester disease; adult T‑cell leukemia/lymphoma (when prescribed in combination with zidovudine); primary cutaneous anaplastic large cell lymphoma (when prescribed as a single agent); mycosis fungoides or Sezary syndrome; chronic myeloid leukemia during pregnancy.

2) Prescribed by or in consultation with an oncologist; 3) For Erdheim‑Chester disease, used as single agent for symptomatic or relapsed/refractory disease; 4) Request must meet ONE of: a) dose supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use, or b) prescribed regimen is FDA‑approved or NCCN‑recommended (prescriber must submit supporting evidence). Approval duration: 6 months.

Initial Approval — Chronic Hepatitis B (CHB)

Covered when ALL of the following are met for chronic hepatitis B (CHB).

CHB initial criteria: 1) Prescribed by or in consultation with a gastroenterologist, hepatologist, or infectious disease specialist; 2) Diagnosis of chronic hepatitis B virus infection; 3) Evidence of viral replication and liver inflammation: elevated ALT (AASLD upper limits referenced) and HBV DNA ≥20,000 IU/mL for HBeAg‑positive members or ≥2,000 IU/mL for HBeAg‑negative members OR diagnosis of cirrhosis with HBV DNA ≥2,000 IU/mL and age >18 years; 4) If age <17 years, member does not have cirrhosis; 5) Liver biopsy showing moderate–severe necroinflammation (grade 9–18) or significant fibrosis (stage 2–4, per 2024 WHO definition) where applicable; 6) Dose does not exceed 180 mcg per week.Dose ≤ 180 mcg/week

Approval duration: 48 weeks.

Continuation/Renewal Criteria

Covered when ALL of the following are met for members currently receiving therapy.

Continuation criteria: 1) Member is currently receiving Pegasys via the Centene benefit or documentation shows member has received Pegasys for at least 30 days; 2) Member is responding positively to therapy; 3) If request is for a dose increase, new dose does not exceed 180 mcg per week OR the new dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).Dose ≤ 180 mcg/week

Approval duration: 12 months (special allowances: up to 5 years total for melanoma; up to a total of 48 weeks for HBV).

Not Recommended for Chronic Hepatitis C

CHC stance: Interferon‑based treatment regimens (including Pegasys) are no longer recommended for chronic hepatitis C per AASLD‑IDSA 2018 guidance due to the availability of direct‑acting antivirals.

Approval duration: Not applicable (use considered not recommended).

Policy-level coverage clarifications and historical updates

Policy‑level coverage clarifications and historical updates.

Duration standardization: Approval duration for melanoma and NCCN‑supported off‑label uses standardized to 6 months initial duration and 12 months continued duration.

Per 3Q2021 annual review.

Maximum dosing for CHB: Pegasys maximum dosing for chronic hepatitis B clarified to 180 mcg/week.180 mcg/week

Per 3Q2022 review.

Significant fibrosis definition: Definition of significant fibrosis updated from stage 3–4 to stage 2–4 per 2024 WHO CHB guidelines.stage 2-4

Per 3Q2024 review.

Requests for peginterferon alfa-2a (Pegasys) for the treatment of chronic hepatitis C (CHC) are not authorized under this policy; interferon-based regimens are no longer recommended for CHC per AASLD‑IDSA guidance and are considered not medically necessary for this indication. Non‑FDA approved indications generally are not addressed in this policy unless there is sufficient supporting documentation of efficacy and safety per applicable off‑label use policies and the member meets the specific criteria described for other covered indications.

The policy has removed osteopenia/osteoporosis as an off‑label indication because it is considered a complication of systemic mastocytosis and therefore is no longer listed among NCCN‑supported off‑label uses for peginterferon alfa‑2a.

Current guidance from AASLD‑IDSA indicates that interferon‑based treatment regimens (including peginterferon alfa‑2a) are no longer recommended for chronic hepatitis C due to availability of effective direct‑acting antivirals; therefore peginterferon alfa‑2a is not considered appropriate first‑line therapy for CHC under this policy and requests for this indication may be denied.

The HCPCS codes listed in this policy (e.g., J3590, S0145) are provided for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage; claims and payment remain subject to the member’s evidence of coverage, plan limitations, state/federal requirements, and applicable Health Plan administrative policies. Providers should submit prior authorization requests with supporting clinical documentation and reference the most current professional coding guidance when billing.

Initial Therapy

Initial therapy

Initial authorization criteria depend on indication.

Initial therapy nodes: For NCCN off‑label oncology uses: meet the listed diagnosis, prescriber is an oncologist or consult obtained, and dosing/regimen is supported by practice guidelines, peer‑reviewed literature, or is FDA‑approved/NCCN‑recommended (prescriber must submit supporting evidence). For CHB: specialist prescriber, documented CHB with required viral replication and inflammation criteria (HBV DNA and ALT/biopsy thresholds), and dose ≤180 mcg/week.Dose ≤180 mcg/week

Approval durations specified per indication (6 months for oncology off‑label; 48 weeks for CHB).

Initial therapy durations

Initial approval durations for select oncology and NCCN‑supported off‑label uses.

Initial approval duration: Initial approval standardized to 6 months for melanoma and NCCN‑supported off‑label uses.6 months

Per 3Q2021 review.

Continuation Therapy

Continuation therapy

Criteria for continuation or dose increases for members already on therapy.

Continuation therapy: Member currently receiving medication via Centene benefit or has received Pegasys for ≥30 days; member is responding positively to therapy; dose increases must not exceed 180 mcg/week unless supported by practice guidelines or peer‑reviewed literature (prescriber must submit evidence).Dose ≤ 180 mcg/week

Approval duration: 12 months (special durations for melanoma and HBV).

Continued therapy durations

Standard continued approval duration for certain oncology and NCCN‑supported off‑label uses.

Continued approval duration standardized to 12 months for melanoma and NCCN‑supported off‑label uses following an initial 6‑month approval.12 months

Per 3Q2021 review.

Coding

HCPCS Codes referencedHCPCS

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

HBV DNA thresholds — CHB treatment

HBeAg-positive CHB treatment thresholdHBV DNA ≥20,000 IU/mL (treatment recommended for immune-active CHB)

HBeAg-negative CHB treatment thresholdHBV DNA ≥2,000 IU/mL (treatment recommended for immune-active CHB and for cirrhosis regardless of ALT)

Cirrhosis-specific thresholdFor diagnosis of cirrhosis, HBV DNA ≥2,000 IU/mL with age >18 qualifies for treatment

ALT upper limits (AASLD)

ALT upper limit (men)35 IU/L

ALT upper limit (women)25 IU/L

Source guidanceAASLD upper limits of normal for serum ALT

Pegasys maximum dosing for CHB

Maximum weekly dose for CHBDo not exceed 180 mcg per week for adults

Approved adult regimen duration (CHB)180 mcg SC per week as monotherapy for 48 weeks

Product references confirming max dosePolicy clarifies Pegasys maximum dosing for CHB is 180 mcg/week

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior Authorization Required: Requests for Pegasys require prior authorization. Provider must demonstrate the member meets all initial approval criteria (diagnosis, prescriber specialty/consultation, and regimen requirements) before approval will be granted.

Prior authorization required for all indications listed under policy
Prescriber specialty or consultation documentation required (e.g., oncologist for oncology/NCCN-supported off-label uses)
Approval durations vary by indication (e.g., 6 months initial for many NCCN off-label uses; continuation criteria may allow 12 months)

Documentation Required

Documentation and Covered Indications

Documentation and Covered Indications: Providers must submit supporting clinical documentation (office chart notes, laboratory results, pathology reports, prior treatment history, and any supporting peer‑reviewed literature or guideline references for off‑label uses) to demonstrate the member meets the policy criteria. Requests for diagnoses not authorized by this policy (for example, treatment of chronic hepatitis C) or lacking adequate documentation may be denied.

Include relevant labs and treatment history to show response to therapy when requesting continuation or dose increases
For off‑label NCCN‑recommended indications, include evidence that the prescribed regimen is FDA‑approved for the regimen or is recommended by NCCN and supporting literature per policy
Requests without sufficient documentation of efficacy/safety for non‑FDA approved indications may be denied

Documentation Required

Policy and Documentation Reminder

Policy and Documentation Reminder: Adhere to the coverage documents, state and federal requirements, and applicable Health Plan administrative policies when submitting requests. This clinical policy is based on current standards and guidance but does not guarantee payment — coverage decisions remain subject to the member's evidence of coverage and plan terms. Providers retain responsibility for clinical judgment and must supply all requested information for timely review.

Coverage subject to terms, conditions, exclusions, and limitations of member's evidence of coverage
When state Medicaid provisions conflict with this policy, state Medicaid provisions take precedence
The Health Plan may change or withdraw this policy; authorization decisions are administrative and require adequate documentation

Background

Peginterferon alfa‑2a (Pegasys) is a pegylated recombinant interferon alfa indicated for select viral hepatitis and NCCN‑supported oncology uses. It is a covalent conjugate of recombinant interferon alfa‑2a administered subcutaneously (product available as prefilled syringes and vials) and has a labeled maximum adult dose of 180 mcg/week for chronic hepatitis B. Pegasys carries boxed warnings and contraindications (including autoimmune hepatitis and hepatic decompensation); providers must follow labeled dosing, specialist prescribing requirements, and submit clinical documentation to support medical necessity for covered indications.

Definitions

Peginterferon alfa-2a (Pegasys) — drug description

Generic / BrandPeginterferon alfa-2a (Pegasys)

DescriptionA covalent conjugate of recombinant interferon alfa-2a (pegylated interferon alfa)

AvailabilityPrefilled syringe and vial presentations (e.g., 180 mcg/0.5 mL syringe; 180 mcg/mL vial)

Significant fibrosis — 2024 WHO CHB definition

Definition of significant fibrosis (WHO 2024)Stage 2–4

ContextPolicy updated definition from stage 3–4 to stage 2–4 per 3Q2024 review

Use in criteriaUsed as a histologic criterion qualifying patients for CHB treatment authorization

Step Therapy

Step	Requirement	Notes
1	Diagnosis clarified to primary cutaneous anaplastic large cell lymphoma (previously described as primary cutaneous CD30+ T‑cell lymphoproliferative disorder).	Per 3Q2025 review; requires monotherapy use per NCCN.

Quantity Limits

Peginterferon alfa-2a (Pegasys) — quantity limit / maximum dose

Maximum single-week quantity180 mcg per week

Administration routeSubcutaneous (per product labeling)

Packaging examplesPrefilled syringe: 180 mcg/0.5 mL; Vial: 180 mcg/mL

Site of Care

Note

Administration/site of care: subcutaneous per product labeling

Administer Pegasys subcutaneously per the product labeling; this policy section does not specify additional site‑of‑care restrictions.

Follow product labeling for subcutaneous administration.
Site‑of‑care restrictions, if any, are not detailed in this portion of the policy.