CurrentAnthemPolicy CC-0020

Natalizumab Agents (Tysabri, Tyruko) — Coverage Criteria

Clinical coverage and prior authorization criteria for natalizumab (Tysabri and biosimilar Tyruko) for relapsing multiple sclerosis and moderate-to-severe Crohn's disease, including enrollment in REMS/TOUCH programs and exclusions.

Policy Summary

PayerAnthem

PolicyNatalizumab Agents (Tysabri, Tyruko) — Coverage Criteria

Policy CodePolicy CC-0020

Change TypeCoding and step therapy updates

Effective Date12/22/2025

Next Review Date

Key ActionObtain prior authorization with documentation of diagnosis, REMS/TOUCH enrollment, JCV antibody testing and prior trial or intolerance to preferred agents as applicable.

SourceLink

POLICY UPDATE CHANGES

Annual Review: Minor wording update. Step therapy and step therapy table updates. Coding Reviewed: Added ICD-10-CM G37.9.

Step therapy table updates on 12/01/2025.

Coding Update: Removed ICD-10-CM G35 effective 9/30/25 and added G35.A, G35.C1 effective 10/1/25.

1 vial/28dquantity limit

TOUCH requiredREMS enrollment

Tyrukobiosimilar included

G35.A,G35.C1,G37.9ICD-10 additions

Coverage Criteria for Natalizumab

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Initial Approval

Requests for Tysabri (natalizumab) may be approved if the following criteria are met:

Primary approval criteria: I. Individual has a diagnosis of relapsing multiple sclerosis (RMS) (including clinically isolated syndrome, relapsing-remitting disease or active secondary progressive disease); AND II. Individual is enrolled in and meeting all conditions of the MS Touch/REMS Prescribing Program; OR III. Individual has a diagnosis of moderate to severe Crohn's disease (CD) and is using Tysabri/Tyruko for induction and maintenance of clinical response and remission; AND IV. Individual has had an inadequate response to or is unable to tolerate conventional Crohn's disease therapies and TNFα inhibitors; AND V. Individual is enrolled in and meeting all conditions of the CD Touch/REMS Prescribing Program; AND VI. Individual has had a John Cunningham virus (JCV) antibody test and the results as well as risks and benefits have been discussed and understood.

MS and CD branches are combined with OR between MS enrollment in REMS and CD criteria; JCV testing required.

Step Therapy / Preferred Agent Requirements

Step therapy criteria for Multiple Sclerosis when requesting natalizumab:

Step therapy options: I. Documentation is provided that individual has been on the natalizumab agent (Tysabri/Tyruko); OR II. Documentation has been provided that individual has had a trial and inadequate response (including but not limited to clinical relapse, new or enlarged lesions on MRI or confirmed disability progression) or intolerance to a preferred agent; OR III. Documentation is provided that individual has high disease activity despite treatment with a disease modifying drug defined as: A. At least one relapse in the previous year while on therapy; AND B. At least 9 T2-hyperintense lesions in cranial MRI; AND C. At least one Gadolinium-enhancing lesion.

Defines acceptable routes to fulfill step therapy: current natalizumab use, failed preferred agent, or meeting high disease activity criteria.

Tysabri (natalizumab) and the biosimilar Tyruko are covered only when the patient meets the program’s specific approval criteria. Requests may be approved when the individual has a diagnosis of relapsing multiple sclerosis (RMS) (including clinically isolated syndrome, relapsing‑remitting MS or active secondary progressive MS) or a diagnosis of moderate‑to‑severe Crohn’s disease being treated for induction and maintenance after inadequate response or intolerance to conventional therapies and TNFα inhibitors, and when all other enrollment and safety conditions are met. Enrollment in and compliance with the applicable TOUCH REMS/Prescribing Program and documentation of a John Cunningham virus (JCV) antibody test with discussion of results and risks/benefits are required prior to approval.

Therapy may not be approved when the coverage criteria above are not fully met. Specific non‑covered indications include use for primary progressive MS or non‑active secondary progressive MS, continued use when the member is responding to and tolerating another effective treatment for MS or Crohn’s disease, a current or prior history of PML, significant immunocompromise (for example, HIV/AIDS, leukemia, lymphoma, or following organ transplantation), or concurrent use with chronic antineoplastics, certain immunosuppressants (e.g., azathioprine), TNFα inhibitors, or other MS disease‑modifying agents. Use outside these criteria or for any other indications is not medically necessary.

Provider Requirements and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for natalizumab agents (Tysabri, Tyruko). Requests may be approved only when diagnosis and program enrollment criteria are met and required testing and counseling have been completed.

Affected products: Tysabri (natalizumab), Tyruko (natalizumab-sztn)
Required diagnosis: relapsing multiple sclerosis (including clinically isolated syndrome, relapsing‑remitting MS, or active secondary progressive MS) OR moderate to severe Crohn's disease for induction/maintenance
REMS/TOUCH: Individual must be enrolled in and meeting all conditions of the MS Touch/REMS or CD Touch/REMS Prescribing Program as applicable
JCV testing: Documentation of John Cunningham virus (JCV) antibody test results and documentation that risks/benefits were discussed and understood

Step Therapy

Step Therapy May Be Required

Step therapy may apply in addition to medical-necessity approval. Even when clinical criteria for natalizumab are met, the member's benefit plan may require trial and failure (or intolerance) of one or more preferred agent(s) before approval of Tysabri/Tyruko.

Benefit-plan level step therapy may require use of a preferred agent(s) first
Preferred products list: refer to the plan-specific preferred product list (link or formulary) to identify preferred agents
If plan step therapy applies, prior authorization must include documentation of the required trial(s) and outcome

Documentation Required

Documentation Expectations for Approvals

Documentation required to satisfy step therapy and prior authorization: provide clear clinical evidence of trials, responses, and current therapy status.

For continuation or prior use: documentation that the individual has been on Tysabri/Tyruko (dates and response)
If seeking approval after failure of preferred agents: documentation of trial and inadequate response or intolerance to preferred agent(s) (examples: clinical relapse, new/enlarged MRI lesions, confirmed disability progression)
When claiming high disease activity: provide supporting evidence per criteria (e.g., ≥1 relapse in prior year while on therapy; ≥9 T2 hyperintense lesions on cranial MRI; ≥1 gadolinium‑enhancing lesion)
Include JCV antibody test result and note of documented discussion of risks/benefits and PML risk

Denial Risk

Common Denial Triggers

Common denial triggers — requests will be denied when clinical criteria, REMS enrollment, step‑therapy, or documentation requirements are not met.

Use for excluded indications: primary progressive MS or non‑active secondary progressive MS
Requests where the member is currently responsive to and tolerating another therapy will be denied
Absence of REMS/TOUCH enrollment or failure to meet REMS program conditions
Missing JCV antibody testing or lack of documented risk/benefit discussion
Use in contraindicated combinations (e.g., chronic antineoplastics, certain immunosuppressants, TNFα inhibitors, or concomitant other MS disease‑modifying agents) will lead to denial

Definitions and Clinical Terms

Relapsing multiple sclerosis (RMS) — definition

Definition of RMSRelapsing multiple sclerosis (RMS) includes clinically isolated syndrome (CIS), relapsing‑remitting MS (RRMS), and active secondary progressive MS (active SPMS)

Clinical contextRMS is an autoimmune inflammatory demyelinating disease of the central nervous system with symptoms such as fatigue, sensory and motor deficits, coordination/balance problems, visual disturbances, and cognitive changes

Treatment goalPrevent relapses and progressive worsening; disease‑modifying therapies are most effective for relapsing forms

Progressive multifocal leukoencephalopathy (PML)

PML descriptionProgressive multifocal leukoencephalopathy (PML) is an opportunistic viral brain infection that usually leads to death or severe disability

Risk factorsRisk increases with duration of natalizumab therapy, prior use of immunosuppressants, and presence of anti‑JCV antibodies

Clinical actionWithhold natalizumab immediately at the first sign or symptom suggestive of PML

G35.A	Relapsing-remitting multiple sclerosis
G35.C1	Active secondary progressive multiple sclerosis
G37.9	Demyelinating disease of central nervous system, unspecified [clinically isolated syndromes]
K50.00-K50.919	Crohn's disease [regional enteritis]
Z01.84	Encounter for antibody response examination

OpenPayer

Natalizumab Agents (Tysabri, Tyruko) — Coverage Criteria

Coverage Criteria for Natalizumab

Coding and Diagnosis Codes

Provider Requirements and Prior Authorization

Background on Natalizumab

Definitions and Clinical Terms

J2323
Q5134