ModifiedCignaPolicy N/A

Hepatology - Rezdiffra Prior Authorization Policy

This Cigna prior authorization policy describes coverage requirements for Rezdiffra (resmetirom) for treatment of non-cirrhotic metabolic dysfunction‑associated steatohepatitis (MASH)/non‑alcoholic steatohepatitis (NASH) with stage F2–F3 fibrosis and applies to providers and members covered under Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyHepatology - Rezdiffra Prior Authorization Policy

Policy CodePolicy N/A

Change TypeModified coverage criteria and documentation requirements (material changes)

Effective DateN/A

Next Review DateApr 8, 2026

Key ActionSubmit prior authorization with documentation confirming MASH/NASH diagnosis and F2–F3 fibrosis by biopsy (within 3 years) or VCTE/MRE/ELF (within 6 months) and prescriber attestation of ONE or more managed metabolic risk factors.

SourceLink

POLICY UPDATE CHANGES

Patients who have completed ≥ 1 year of therapy with Rezdiffra are now reviewed under the same continuation criteria previously applied to patients after ≥ 2 years of therapy.

The required NAFLD activity score criteria for liver biopsy was modified to require a score ≥1 in steatosis, ballooning, and lobular inflammation (previously >1 in all three and total NAS ≥4).

Imaging timeframe for documentation was changed from within 3 months to within 6 months preceding treatment.

The condition language was updated to remove 'with moderate to advanced liver fibrosis' while retaining requirement that patients demonstrate moderate or advanced fibrosis for initial therapy.

The requirement that the diagnosis be 'prior to treatment with Rezdiffra' was removed.

Number of metabolic risk factors required was changed to ONE or more (previously three or more).

Diagnosis of stage F2 or F3 fibrosis must be documented by one of: liver biopsy within 3 years; VCTE, MRE, or ELF within 6 months (ELF score ≥ 9.2 to ≤ 10.5).

Criteria were updated to include Wegovy (injection, HD injection, and tablet) alongside Rezdiffra where referenced for fibrosis documentation.

For patients currently receiving Rezdiffra the prior requirement that prescriber attest patient has not progressed to F4 was modified to state the prescriber reports the patient does not have cirrhosis (F4); later the requirement that patient does not have cirrhosis was removed because cirrhosis is addressed in conditions not recommended for approval.

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1 yearapproval duration

F2–F3required fibrosis

9.2–10.5ELF acceptable range

3 yrsbiopsy recency

6 monthsimaging/ELF recency

F4not recommended

Coverage Criteria for Rezdiffra (resmetirom)

FDA‑Approved Indication — Initial Therapy

Approve for 1 year if the patient meets ALL of the following (A.i–vi):

Initial Therapy criteria: i. Patient is ≥ 18 years of age; AND ii. Patient has stage F2 or F3 fibrosis prior to initiating treatment identified by ONE of: (a) liver biopsy within 3 years; OR (b) VCTE within 6 months; OR (c) MRE within 6 months; OR (d) ELF within 6 months with score ≥9.2 to ≤10.5; AND iii. According to the prescriber, patient has ONE or more managed metabolic risk factors (central obesity, hypertriglyceridemia, reduced HDL, hypertension, elevated fasting plasma glucose); AND iv. According to the prescriber, alcohol consumption <20 g/day for females OR <30 g/day for males; AND v. Medication will be used in combination with diet and exercise; AND vi. Prescribed by or in consultation with an endocrinologist, gastroenterologist, or hepatologist.

FDA‑Approved Indication — Continuing Therapy (Currently Receiving Rezdiffra)

Approve for 1 year if the patient meets ALL of the following (B.i–v):

Continuation Therapy criteria: i. Patient has completed ≥1 year of therapy with Rezdiffra AND according to the prescriber the patient has not had worsening of fibrosis or MASH/NASH; AND ii. According to the prescriber, metabolic risk factors are managed according to standard of care; AND iii. According to the prescriber, alcohol consumption <20 g/day for females OR <30 g/day for males; AND iv. Medication will be used in combination with diet and exercise; AND v. Medication is prescribed by or in consultation with an endocrinologist, gastroenterologist, or hepatologist.

Initial Therapy

Covered when ALL of the following are met

Diagnosis and Fibrosis Staging: Documentation of MASH/NASH with stage F2 or F3 fibrosis prior to initiating treatment, confirmed by ONE of: liver biopsy within 3 years; VCTE within 6 months; MRE within 6 months; ELF test within 6 months with score 9.2–10.5.as specified

Imaging exams must be within 6 months; biopsy within 3 years.

Metabolic Risk Factors: According to the prescriber, the patient has ONE or more metabolic risk factors (e.g., central obesity, hypertriglyceridemia, reduced HDL, hypertension, elevated fasting plasma glucose indicative of diabetes or pre-diabetes) managed according to standard of care.ONE or more

Changed from three or more to one or more.

Continuation Therapy / Currently Receiving Rezdiffra

Covered when ALL of the following are met

Duration threshold for review: Patient has completed ≥ 1 year of therapy with Rezdiffra and is reviewed under continuation criteria previously applied after ≥ 2 years.≥ 1 year

Continuation criteria applied earlier (after 1 year) per revision.

Prescriber assessment: According to the prescriber, patient has not had worsening of fibrosis or MASH/NASH; prior versions required attestation patient has not progressed to F4 but language was modified/removed as cirrhosis is addressed separately.prescriber statement

Attestation language refined and later removed as redundant.

Rezdiffra (resmetirom) is considered not medically necessary for any other uses outside the specific covered indication. This explicitly includes use for Metabolic Dysfunction‑Associated Steatotic Liver Disease (MASLD)/Non‑Alcoholic Fatty Liver Disease (NAFLD) and other indications not meeting the policy's documented MASH/NASH with F2–F3 fibrosis criteria.

MASH/NASH with cirrhosis (stage F4) is identified in this policy as a condition not recommended for approval. The safety and effectiveness of Rezdiffra have not been established in patients with NASH cirrhosis, and use in these patients is excluded from coverage consideration under this policy.

Use of Rezdiffra for MASLD/NAFLD or for NASH with cirrhosis (F4) is defined as not medically necessary under this policy. Requests for these indications do not meet the documented coverage criteria and may be denied.

Use of Rezdiffra in patients with cirrhosis (stage F4) is explicitly called out as not recommended for approval. The policy treats cirrhosis (F4) as an exclusion and may deny prior authorization or coverage when cirrhosis is present.

Coding and Test Thresholds

Noninvasive and laboratory thresholds — key values

VCTE liver stiffness≥ 8.5 kPa (trial prescreening threshold referenced)

Controlled Attenuation Parameter (CAP)≥ 280 dB/m

ELF score range (for detecting ≥F2 and documenting F2–F3)ELF ≥ 9.2 to ≤ 10.5 (ELF cutoff 9.2 provides optimal sensitivity/specificity for detecting ≥F2)

ELF score — acceptable documentation range

Acceptable ELF score range for documentation≥ 9.2 to ≤ 10.5

Purpose of cutoff 9.2Cutoff of 9.2 provides optimal sensitivity and specificity for detecting ≥F2 fibrosis

Guidance for values outside range

Prior Authorization, Documentation, and Prescriber Requirements

Prior Authorization

Prior Authorization Required

Prior Authorization is recommended for prescription benefit coverage of Rezdiffra. All approvals are provided for the duration noted in the policy. Because of the specialized skills required for evaluation and diagnosis and monitoring, Rezdiffra must be prescribed by or in consultation with a physician who specializes in the condition being treated (e.g., endocrinologist, gastroenterologist, or hepatologist).

Prior authorization recommended for Rezdiffra (prescription benefit).
Prescriber must be a specialist or consult a specialist (endocrinologist, gastroenterologist, or hepatologist).

Documentation Required

Documentation is required for use of Rezdiffra as specified in the clinical criteria. Documentation may include chart notes, laboratory results, medical test results, claims records, prescription receipts, and/or other information and must include patient-specific identifying information.

Background — Drug and Indication

Rezdiffra (resmetirom) is a thyroid hormone receptor‑beta (THR‑β) agonist approved for use in combination with diet and exercise for adults with non‑cirrhotic metabolic dysfunction‑associated steatohepatitis (MASH)/non‑alcoholic steatohepatitis (NASH) who have stage F2–F3 fibrosis. Clinical trial evidence (MAESTRO‑NASH) demonstrated improvements in NASH resolution and fibrosis at Week 52 in biopsy‑confirmed patients with metabolic risk factors. The policy requires documentation of F2–F3 fibrosis by acceptable tests (e.g., liver biopsy, VCTE, MRE, or ELF) and prior authorization per the stated criteria.

Definitions and Test Descriptions

MASH/NASH — definition and treatment context

DefinitionMetabolic dysfunction‑associated steatohepatitis (MASH), also called non‑alcoholic steatohepatitis (NASH), is steatosis plus hepatocellular inflammation and injury; diagnosis is confirmed by histology (biopsy) but noninvasive tests (VCTE, MRE, ELF) are used to assess fibrosis.

Typical fibrosis stages for treatmentNon‑cirrhotic MASH/NASH with stage F2–F3 fibrosis

Associated managementTreatment is indicated in combination with diet and exercise and requires specialist prescribing or consultation

ELF test — description and acceptable score range

Test nameEnhanced Liver Fibrosis (ELF) test

Acceptable score range for documenting F2–F3 fibrosisELF score ≥ 9.2 to ≤ 10.5

Policy Summary

PayerCigna

PolicyHepatology - Rezdiffra Prior Authorization Policy

Policy CodePolicy N/A

Change TypeModified coverage criteria and documentation requirements (material changes)

Effective DateN/A

Next Review DateApr 8, 2026

SourceLink

On This Page

Values above the upper range warrant exclusion of cirrhosis/portal hypertension using VCTE or MRE

All documentation referenced in criteria must be submitted with prior authorization request.
Documentation may include biopsy reports, VCTE/MRE results, ELF test results, lab reports, and clinical notes.

Denial Risk

Denial Triggers

Claims submitted without covered diagnosis or procedure codes or without the documentation required by the criteria may be denied. Rezdiffra is considered not medically necessary for indications not supported by the criteria (see Conditions Not Covered).

Claims without covered diagnosis/procedure codes will be denied.
Use for unsupported indications (e.g., MASLD/NAFLD alone or other non-covered uses) may be denied as not medically necessary.

Documentation Required

Required Diagnostic and Staging Documentation

For approval of Rezdiffra for MASH/NASH, documentation must confirm the diagnosis and staging showing F2 or F3 fibrosis by ONE of the following: liver biopsy within 3 years, VCTE performed within 6 months, MRE performed within 6 months, or ELF test performed within 6 months with a score of ≥ 9.2 to ≤ 10.5. Absence of qualifying fibrosis documentation may result in denial. Use in patients with cirrhosis (F4) is not recommended for approval and may be denied.

Liver biopsy documenting F2 or F3 fibrosis within 3 years prior to treatment.
VCTE (transient elastography) showing F2 or F3 within 6 months prior to treatment.
MRE showing F2 or F3 within 6 months prior to treatment.
ELF test within 6 months with score ≥ 9.2 and ≤ 10.5.

Documentation Required

Metabolic Risk Factors Documentation

Prescriber documentation must state that the patient has ONE or more metabolic risk factors managed according to standard of care. The metabolic risk factors include central obesity, hypertriglyceridemia, reduced HDL cholesterol, hypertension, and elevated fasting plasma glucose indicative of diabetes or pre-diabetes.

At least ONE of the following documented and managed per standard of care: central obesity; hypertriglyceridemia; reduced HDL cholesterol; hypertension; elevated fasting plasma glucose (diabetes or pre-diabetes).
Prescriber attestation that the risk factors are being managed should be included in the record.

Note

Wegovy Referenced

Criteria and staging requirements reference prior or concurrent use considerations with Wegovy formulations. Documentation of F2–F3 fibrosis prior to initiating treatment applies when treatment involves Rezdiffra or Wegovy (Wegovy injection, Wegovy HD injection, or Wegovy tablet) as specified in the clinical criteria.

References to Wegovy (injection, HD injection, and tablet) are included in fibrosis documentation timing and acceptable tests.
If treatment involves Wegovy formulations, submit the same qualifying fibrosis documentation listed for Rezdiffra.

Clinical roleBlood-based noninvasive biomarker supported for fibrosis estimation alongside VCTE and MRE; cutoff 9.2 optimizes detection of ≥F2