ModifiedEmblemHealthPolicy MG.MM.PH.108

Tysabri (natalizumab) Intravenous

Defines medical necessity, authorization, dosing, and renewal criteria for natalizumab (Tysabri) for EmblemHealth members with relapsing forms of multiple sclerosis or moderately to severely active Crohn's disease, and lists applicable codes and limitations.

Policy Summary

PayerEmblemHealth

PolicyTysabri (natalizumab) Intravenous

Policy CodePolicy MG.MM.PH.108

Change TypeMaterial clinical revisions

Effective Date

Next Review DateFeb 10, 2025

Key ActionSubmit prior authorization with documentation of confirmed diagnosis (e.g., MRI for MS) and required prior therapy trials for Crohn's (one oral immunosuppressive ≥3 months and one TNF-inhibitor ≥3 months) as applicable.

SourceLink

POLICY UPDATE CHANGES

Removed requirement that MS patients must have experienced inadequate efficacy or intolerance to one disease-modifying agent and detailed 'highly active' or rapidly advancing disease language.

Removed requirement that Crohn's patients must have tried at least two biologics.

MS initial criteria replaced with: 'Patient has confirmed diagnosis of MS as documented by a laboratory report (i.e., MRI) AND used as single agent therapy.'

Multiple Sclerosis initial criteria were revised to replace a multi-item list with: 'Patient has confirmed diagnosis of MS as documented by a laboratory report (i.e MRI): AND Used as single agent therapy'.

Crohn's disease criteria were revised from requiring trials of two biologics to requiring baseline disease severity assessment, trial and failure on one oral immunosuppressive for ≥3 months (unless contraindicated), and trial and failure on one TNF-inhibitor for ≥3 months (unless contraindicated).

Removal of requirement for documented negative JCV antibody ELISA test within past 6 months from initial and renewal criteria.

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Coverage Criteria

inv-01: Initial Therapy

Covered when ALL of the following are met:

General requirements: Patient is at least 18 years old; Prescriber and patient are enrolled in and meet the conditions of the TOUCH program; Not used in combination with antineoplastic, immunosuppressant, or immunomodulating agents; Patient does not have a systemic medical condition resulting in significantly compromised immune system function.

Multiple Sclerosis specific: Patient has a relapsing form of multiple sclerosis and has a confirmed diagnosis of MS documented by a laboratory report (e.g., MRI); medication is used as single-agent therapy.

Relapsing forms include clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease.

Crohn's disease specific: Patient has moderately to severely active Crohn's disease; physician has assessed baseline disease severity using an objective measure/tool; documented trial and failure of ONE oral immunosuppressive therapy for at least 3 months unless contraindicated (examples: corticosteroids, methotrexate, azathioprine, 6-mercaptopurine); documented trial and failure of ONE TNF-inhibitor therapy for at least 3 months unless contraindicated (examples: infliximab, certolizumab, adalimumab); used as single-agent therapy (not concurrent with another biologic or immunosuppressant).

Initial coverage provided for 12 weeks.

inv-02: Continuation/Renewal Therapy

Authorizations can be renewed when ALL of the following are met:

General renewal: Patient continues to meet the initial approval criteria and there is an absence of unacceptable toxicity from the drug (examples include hypersensitivity reactions, hepatotoxicity, signs/symptoms of progressive multifocal leukoencephalopathy [PML], development of severe infections).

MS renewal: Continuous monitoring demonstrates response or absence of unacceptable toxicity. Inadequate response is defined as ≥1 relapse, ≥2 new MRI-detected lesions, or increased disability on examination over a one-year period. Discontinue therapy in patients with persistent neutralizing natalizumab antibodies.

Examples of monitoring: annualized relapse rate (ARR), new/worsening MRI lesions, EDSS, T25-FW, 9-HPT.

Crohn's renewal: Initial renewal: clinical response or remission is seen by 12 weeks. Second renewal: patient has been tapered off oral corticosteroids within six months of starting therapy AND disease response evidenced by improvement in signs/symptoms or objective scoring tools (e.g., CDAI, Harvey-Bradshaw). All subsequent renewals: patient does not require steroid use that exceeds three months in a calendar year AND ongoing disease response compared to baseline.

inv-03: Not Medically Necessary / Exclusions

Not covered uses: Tysabri (natalizumab) is not considered medically necessary for indications other than relapsing forms of multiple sclerosis and moderately to severely active Crohn's disease due to insufficient evidence of therapeutic value.

inv-04: Initial Therapy (per indication)

Initial therapy coverage criteria (per indication) — covered when ALL of the following are met

Crohn's disease initial criteria: Physician has assessed baseline disease severity utilizing an objective measure/tool; AND documented trial and failure on ONE oral immunosuppressive therapy for at least 3 months unless contraindicated (examples: corticosteroids, methotrexate, azathioprine, 6-mercaptopurine); AND documented trial and failure on ONE TNF-inhibitor therapy for at least 3 months unless contraindicated (examples: infliximab, certolizumab, adalimumab); AND used as single-agent therapy (not concurrent with another biologic or immunosuppressant).see text

Replaces prior requirement for trials of at least two biologics.

Multiple Sclerosis initial criteria: Patient has a confirmed diagnosis of multiple sclerosis documented by a laboratory report (e.g., MRI); AND medication is used as single-agent therapy.see text

Simplified from prior multi-part criteria.

Tysabri (natalizumab) is not considered medically necessary for indications other than relapsing forms of multiple sclerosis and moderately to severely active Crohn's disease due to insufficient evidence of therapeutic value.

Tysabri (natalizumab) must not be used concurrently with another biologic drug or immunosuppressant (for example: 6-mercaptopurine, azathioprine, cyclosporine, methotrexate). Concurrent use with other immunosuppressive or immunomodulating agents is excluded from coverage.

Any indication that is not explicitly listed in this policy (see the covered indications for relapsing forms of multiple sclerosis and moderately to severely active Crohn's disease) is considered not medically necessary and is excluded from coverage.

Requests that do not include the required prior trials or documentation will be considered inconsistent with the coverage criteria. For Crohn's disease this includes absence of documentation of baseline disease severity or documented trial and failure on the required prior therapies (e.g., one oral immunosuppressive for ≥3 months and one TNF-inhibitor for ≥3 months, unless contraindicated). For multiple sclerosis this includes lack of a confirmed diagnosis (for example, MRI) or failure to demonstrate single‑agent use.

Coding

Applicable Procedure CodesHCPCSCovered

J2323	Injection, natalizumab, 1 mg.
Q5134	Injection, natalizumab-sztn (tyruko) biosimilar, 1 mg

Applicable NDCsNDCCovered

64406-0008-01	Tysabri 300 mg/15 mL single-use vial
61314-0543-94	Tyruko (natalizumab-sztn) injection, 300 mg/15 mL (20 mg/mL) single-dose vial per carton

ICD-10 Diagnoses listedICD-10

G35	Multiple Sclerosis
K50.011	Crohn's disease of small intestine with rectal bleeding
K50.012	Crohn's disease of small intestine with intestinal obstruction
K50.013	Crohn's disease of small intestine with fistula
K50.014	Crohn's disease of small intestine with abscess
K50.018	Crohn's disease of small intestine with other complication
K50.019	Crohn's disease of small intestine with unspecified complications
K50.10	Crohn's disease of large intestine without complications
K50.111	Crohn's disease of large intestine with rectal bleeding
K50.112	Crohn's disease of large intestine with intestinal obstruction

1–10 of 28

1/3

ICD-10 Diagnoses for Crohn's diseaseICD-10Covered

K50.90	Crohn's disease, unspecified, without complications.
K50.911	Crohn's disease, unspecified, with rectal bleeding.
K50.912	Crohn's disease, unspecified, with intestinal obstruction.
K50.913	Crohn's disease, unspecified, with fistula.
K50.914	Crohn's disease, unspecified, with abscess.
K50.918	Crohn's disease, unspecified, with other complication.
K50.919	Crohn's disease, unspecified, with unspecified complications.

Inadequate response definition (MS)

Inadequate response (MS)Defined as ≥1 relapse and/or ≥2 new MRI-detected lesions, or increased disability on examination over a one‑year period.

Monitoring examplesAnnualized relapse rate (ARR), new/worsening T2 hyperintensities or enhancing lesions on brain/spinal MRI, EDSS, T25‑FW, 9‑HPT.

Action on inadequate responseConsider therapy change or discontinuation if inadequate response is documented despite adherence and sufficient treatment duration.

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests. Initial approval requires the patient be ≥ 18 years old, the prescriber and patient be enrolled in and meet TOUCH program conditions, therapy is not used in combination with other antineoplastic, immunosuppressant, or immunomodulating agents, and the patient must not have a systemic medical condition causing significantly compromised immune function.

Applies to all indications in this policy
Prescriber and patient enrollment in TOUCH program required

Documentation Required

Documentation Required for Review

The treating provider must submit complete clinical documentation demonstrating the member meets all applicable criteria. Lack of submitted evidence will prevent proper review and may result in denial.

Clinical evidence must be provided with the preauthorization request
If documentation is missing or incomplete, the request may be denied

Initial Therapy Criteria

inv-25: Initial Drug Therapy

Initial therapy coverage and prerequisites

General: Age ≥18; Prescriber and patient enrolled in TOUCH program; not used concurrently with antineoplastic, immunosuppressant, or immunomodulating agents; no systemic medical condition causing significantly compromised immune system function.

MS: Relapsing form of multiple sclerosis with confirmed diagnosis documented by a laboratory report (e.g., MRI); medication used as single-agent therapy.

Crohn's: Moderately to severely active Crohn's disease; physician-assessed baseline disease severity with an objective tool; documented trial and failure on ONE oral immunosuppressive therapy for ≥3 months unless contraindicated; documented trial and failure on ONE TNF-inhibitor therapy for ≥3 months unless contraindicated; single-agent use only.

Initial coverage provided for 12 weeks.

Continuation / Renewal Criteria

inv-27: Continuation Therapy

Renewal/continuation requirements

General continuation: Patient continues to meet initial criteria and has no unacceptable toxicity (examples: hypersensitivity, hepatotoxicity, signs/symptoms of PML, severe infections).

MS continuation: Monitoring demonstrates response or stable disease; inadequate response defined as ≥1 relapse, ≥2 new MRI lesions, or increased disability over one year; discontinue for persistent neutralizing antibodies.

Crohn's continuation: Initial renewal: clinical response/remission by 12 weeks. Second renewal: tapered off oral corticosteroids within six months of starting therapy AND disease response shown by improvement in signs/symptoms or objective scoring tools (e.g., CDAI, Harvey-Bradshaw). Subsequent renewals: limited steroid use (does not exceed three months in a calendar year) AND ongoing disease response compared to baseline.

Step Therapy Requirements

Step	Required prior therapy (Crohn's disease)	Duration / notes
Step 1	Documented trial and failure on ONE oral immunosuppressive therapy (examples: corticosteroids, methotrexate, azathioprine, and/or 6-mercaptopurine)	At least 3 months unless contraindicated

Step	Required prior therapy (Crohn's disease)	Duration / notes
Step 2	Documented trial and failure on ONE TNF-Inhibitor therapy (examples: infliximab, certolizumab, adalimumab)	At least 3 months unless contraindicated

Summary	Required sequence	Coverage implication
For Crohn's disease, sequential step therapy is required prior to coverage of certain biologics (including natalizumab)	Patient must fail ONE oral immunosuppressive therapy for ≥3 months (unless contraindicated) AND then fail ONE TNF-inhibitor therapy for ≥3 months (unless contraindicated)	Coverage considered only after documented trials and failures of both specified therapy classes in sequence; baseline disease severity assessment also required per policy

Quantity Limits

Tysabri (natalizumab) — quantity limit

Maximum units per dose300 billable units (per dose).

Dosing intervalEvery 28 days (per policy dosing schedule).

Relevant procedure codeHCPCS J2323 = Injection, natalizumab, 1 mg (billable units map to J2323).

Site of Care

Note

Infusion: IV over one hour every 4 weeks

Administration is intravenous at a dose of 300 mg given over one hour every four weeks.

Dose/interval: 300 mg IV over one hour every 28 days.

Note

Permitted administration settings per agent

Appendix lists modes of administration (oral, injection self‑administered, intravenous infusion) indicating permitted settings per agent (infusion center, home, office) as applicable.

Biosimilar Information

Billing Rule

Biosimilar (Tyruko) listed alongside Tysabri

Biosimilar Q5134 and the NDC for Tyruko (natalizumab‑sztn) are listed alongside Tysabri codes/NDCs as applicable products.

Procedure codes include J2323 and Q5134.
NDCs include Tysabri 64406-0008-01 and Tyruko 61314-0543-94.

Background

Natalizumab (Tysabri) is an integrin receptor antagonist indicated for treatment of relapsing forms of multiple sclerosis as monotherapy and for inducing and maintaining response/remission in moderately to severely active Crohn's disease in adults who have had inadequate response to or are intolerant of conventional therapies and TNF inhibitors. Enrollment of the prescriber and patient in the TOUCH safety program is required for use due to safety monitoring considerations.

Definitions

Relapsing forms of MS — definition

Included conditionsRelapsing forms of multiple sclerosis: clinically isolated syndrome, relapsing‑remitting disease, and active secondary progressive disease.

Indication noteTysabri is indicated as monotherapy for relapsing forms of MS in adults.

Documentation requiredConfirmed diagnosis documented by a laboratory report (e.g., MRI) is required for authorization and renewal monitoring.

Disease‑modifying therapies (MS) — appendix

Appendix therapiesAppendix lists disease‑modifying MS therapies (examples include Aubagio, Avonex, Gilenya, Ocrevus, Tysabri).

Administration modesAppendix indicates modes of administration for agents: oral, self‑administered injection, intravenous infusion.

Policy Summary

PayerEmblemHealth

PolicyTysabri (natalizumab) Intravenous

Policy CodePolicy MG.MM.PH.108

Change TypeMaterial clinical revisions

Effective Date

Next Review DateFeb 10, 2025

SourceLink

On This Page

Documentation Required

Required Clinical Documentation

For all requests include documentation confirming the diagnosis and baseline disease assessment as applicable to the indication. Examples: MRI or other diagnostic reports confirming multiple sclerosis; an objective baseline disease severity assessment/tool for Crohn's disease. Include documentation of prescriber specialty or consultation when required (e.g., neurologist for MS).

MS: Confirmed diagnosis of relapsing MS documented by MRI or other diagnostic report
Crohn's disease: Baseline disease severity documented using an objective measure/tool
Include consult notes or prescriber specialty as applicable

Step Therapy

Step Therapy for Crohn's Disease

Stepwise prior therapy must be shown for Crohn's disease: documented trial and failure of ONE oral immunosuppressive therapy for ≥ 3 months (unless contraindicated) and documented trial and failure of ONE TNF-inhibitor for ≥ 3 months (unless contraindicated). The requested biologic must be used as single-agent therapy (not concurrent with another biologic or immunosuppressant).

Oral immunosuppressive trial examples: corticosteroids, methotrexate, azathioprine, 6‑mercaptopurine
TNF‑inhibitor examples: infliximab, certolizumab, adalimumab
A previous trial of the requested biologic or its biosimilar does not count toward biologic trial requirements

Crohn's initial authorization: Documentation must show baseline disease severity assessment using an objective tool; trial and failure on ONE oral immunosuppressive therapy for ≥3 months unless contraindicated; trial and failure on ONE TNF-inhibitor therapy for ≥3 months unless contraindicated; and single-agent use (not concurrent with another biologic or immunosuppressant).

A previous trial of the requested biologic (or its biosimilar) does not count toward required prior biologic trials.

MS initial authorization: Documentation must include confirmed diagnosis of MS (e.g., MRI) AND evidence the medication will be used as single-agent therapy.

Replaces prior expanded criteria set.