CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Natalizumab products: Tysabri, Tyruko

Policy governs coverage, initial and renewal clinical criteria, dosing, coding, and quantity limits for natalizumab (Tysabri and biosimilar Tyruko) for Medicaid, Commercial, and Medicare members of Neighborhood Health Plan of Rhode Island.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyNatalizumab products: Tysabri, Tyruko

Policy CodePolicy N/A

Change TypeClarified (reference updates)

Effective DateJan 1, 2020

Next Review Date

Key ActionRequests must document indication-specific criteria, JCV antibody ELISA within 6 months, prior biologic failures for Crohn's, confirmation of MS diagnosis (e.g., MRI), and that natalizumab will be used as single-agent therapy; Medicare NCD/LCD supersede where applicable

SourceLink

POLICY UPDATE CHANGES

Review dates updated through 02/17/2026 with references updated to 2025/2026 package inserts

2Covered Indications

300 units/28dQuantity Limit

>=18Minimum Age

Coverage Summary

This policy covers natalizumab products (Tysabri and biosimilar Tyruko) and is covered with criteria for Medicaid, Commercial, and Medicare members of Neighborhood Health Plan of Rhode Island. Natalizumab is an integrin receptor antagonist indicated for relapsing forms of multiple sclerosis and moderate to severe Crohn's disease, with evidence showing reductions in relapse rates and risk of disability progression in MS. The policy defines initial and renewal clinical criteria, dosing, coding, and a quantity limit of 300 billable units every 28 days.

Quick thresholds

Age>= 18 years

JCV antibody test recencyDocumented JCV antibody ELISA within past 6 months

Max units per dosing interval300 billable units every 28 days

MS inadequate response definition (renewal)>= 1 relapse OR >= 2 new MRI-detected lesions OR increased disability over 1 year

Crohn's prior anti-TNF requirementFailure/intolerance/contraindication to infliximab or adalimumab for >= 3 months at max tolerated doses

Applicable Codes

HCPCS codesHCPCSCovered

J2323	Injection, natalizumab, 1 mg (Tysabri only)
Q5134	Injection, natalizumab-sztn (Tyruko), biosimilar, 1 mg (Tyruko only)

NDC codesNDC

64406-0008-xx	Tysabri 300 mg/15 mL single-dose vial
61314-0543-xx	Tyruko 300 mg/15 mL single-dose vial

Covered Diagnosis Codes (ICD-10)ICD-10Covered

G35	Multiple Sclerosis
K50.00	Crohn's disease of small intestine without complications
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

1–10 of 29

1/3

mixed

No codes listed

Provider Actions & Billing Rules

Prior Authorization

Prior authorization required

Requests must document indication-specific criteria, a documented JCV antibody ELISA within the past 6 months, prior biologic failures for Crohn's (infliximab or adalimumab for ≥3 months at max tolerated doses), confirmation of MS diagnosis (e.g., MRI per diagnostic criteria), and that natalizumab will be used as single-agent therapy.

Documentation Required

JCV antibody testing documentation

Attach documented JCV antibody ELISA test result within the past 6 months to support approval.

Documentation Required

MS diagnostic documentation

Provide confirmatory diagnostic documentation for MS such as MRI or CSF results per McDonald criteria or defined MS diagnostic criteria.

Billing Rule

Dose and dosing frequency

Administer 300 mg IV over one hour every 4 weeks; bill per HCPCS unit where 1 unit = 1 mg.

J2323
Q5134

Billing Rule

Quantity limit per interval

Limit of 300 billable units every 28 days.

J2323
Q5134

Denial Risk

Concurrent immunosuppressant use

Claims may be denied if natalizumab is used in combination with antineoplastic, immunosuppressant, or immunomodulating agents.

Denial Risk

Crohn's prior anti-TNF requirement

For Crohn's, approval at initiation requires prior failure, intolerance, or contraindication to infliximab IV or adalimumab for at least 3 months at maximum tolerated doses; absence of this requirement may lead to denial.

Clinical Evidence

68%Reduced annualized relapse rate vs placebo (AFFIRM)

42%Reduced risk of disability progression vs placebo (SENTINEL)

Safety concerns include a boxed warning for risk of progressive multifocal leukoencephalopathy (PML). Other notable adverse events and safety issues described in the policy and renewal criteria include infusion reactions, various infections (including herpes infections and opportunistic infections), hepatotoxicity, and antibody formation/neutralizing antibodies which may necessitate therapy discontinuation.

Background & Definitions

Natalizumab is an integrin receptor antagonist approved for treatment of relapsing forms of multiple sclerosis and for moderate to severe Crohn's disease. The standard dosing for all indications is 300 mg IV administered over one hour every four weeks. The policy highlights the PML risk

Term	Definition
Used as single agent therapy	Not used concurrently with another biologic drug, targeted synthetic therapy, or immunosuppressant for the same indication
Active secondary progressive MS (SPMS)	EDSS >= 3.0; disease progressive ≥ 3 months after an initial relapsing‑remitting course plus either ≥1 relapse in the previous 2 years or MRI activity (gadolinium‑enhancing or new/enlarging T2 lesions)

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyNatalizumab products: Tysabri, Tyruko

Policy CodePolicy N/A

Change TypeClarified (reference updates)

Effective DateJan 1, 2020

Next Review Date

SourceLink

On This Page

OpenPayer

Natalizumab products: Tysabri, Tyruko

Coverage Summary

Initial Therapy Criteria

Continuation / Renewal Criteria

Applicable Codes

Provider Actions & Billing Rules

Clinical Evidence

Background & Definitions

Revision History