Centene natalizumab coverage update

Coverage and Medical Necessity Criteria

inv-01: Initial Therapy - Multiple Sclerosis

Covered when ALL of the following are met

MS Initial Approval: 1. Diagnosis of one of: (a) clinically isolated syndrome with contraindication to or clinically significant adverse effects from an interferon‑beta agent or glatiramer; (b) relapsing‑remitting MS with either (i) failure of dimethyl fumarate, teriflunomide, fingolimod, and an interferon‑beta or glatiramer at maximally indicated doses unless contraindicated/adverse effects OR (ii) highly active MS with failure of fingolimod at maximally indicated doses unless contraindicated; (c) secondary progressive MS; 2. Prescribed by or in consultation with a neurologist; 3. Age ≥ 18 years; 4. Not prescribed concurrently with other disease modifying therapies for MS (see Appendix D); 5. Dose does not exceed 300 mg (1 vial) every 4 weeks.age >= 18

Approval duration: Medicaid/HIM/ICHRA 12 months; Commercial 6 months or to member renewal date

inv-02: Initial Therapy - Crohn's Disease (Medicaid)

Covered when ALL of the following are met (Medicaid only)

CD Initial Approval (Medicaid): 1. Diagnosis of Crohn's disease; 2. Prescribed by or in consultation with a gastroenterologist; 3. Age ≥ 18 years; 4. Failure of a ≥3 consecutive month trial of at least one immunomodulator (azathioprine, 6‑MP, methotrexate) at up to maximally indicated doses unless contraindicated OR medical justification supports inability to use immunomodulators; 5. Failure of one adalimumab product used ≥3 months OR history of failure of two TNF blockers; 6. Failure of a ≥3 consecutive month trial of one ustekinumab product unless contraindicated (prior authorization may be required); 7. Not prescribed concurrently with immunosuppressants (e.g., azathioprine, cyclosporine, 6‑MP, MTX) or TNFα inhibitors (aminosalicylates may be continued); 8. Dose does not exceed 300 mg (1 vial) every 4 weeks.age >= 18

Approval duration: 12 months

inv-03: Continued Therapy - Multiple Sclerosis

Covered when ALL of the following are met

MS Continued Therapy: 1. Member is currently receiving medication via Centene benefit or previously met initial approval criteria OR member is in a continuity‑of‑care state/product; 2. Member is responding positively to therapy; 3. Tysabri/Tyruko is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D); 4. If request is for a dose increase, new dose does not exceed 300 mg (1 vial) every 4 weeks.

Approval duration: Medicaid/HIM/ICHRA 12 months; Commercial 6 months or to member renewal date

inv-04: Continued Therapy - Crohn's Disease (Medicaid)

Covered when ALL of the following are met (Medicaid only)

CD Continued Therapy (Medicaid): 1. Member is currently receiving medication via Centene benefit or previously met initial approval criteria OR member is in a continuity‑of‑care state/product; 2. Member is responding positively to therapy; 3. Tysabri/Tyruko is not prescribed concurrently with immunosuppressants (e.g., azathioprine, cyclosporine, 6‑MP, MTX) or TNFα inhibitors (aminosalicylates may be continued); 4. If request is for a dose increase, new dose does not exceed 300 mg (1 vial) every 4 weeks.

Approval duration: 12 months

inv-05: Other indications / Off‑label referral

Other uses

Other Indications: 1. If this drug has recently (within the last 6 months) undergone a label change that is not yet reflected in this policy, follow the applicable no‑coverage or non‑formulary policy for the relevant line of business (see policy references); 2. If the requested use is not specifically listed in authorized indications and criterion 1 does not apply, refer to the off‑label use policy for the relevant line of business.

Refer to CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16, CP.CPA.09, HIM.PA.154, CP.PMN.53

inv-05: Indication-specific coverage (Relapsing MS; Crohn's Disease)

Covered when criteria for indication-specific use and safety are met

Relapsing MS coverage: Member has relapsing MS indication and therapy is prescribed as a disease‑modifying therapy; dosing 300 mg IV every 4 weeks (300 mg/15 mL vial); REMS enrollment (TOUCH) and contraindication screening required (no history of PML, no hypersensitivity to product).

Initial approval durations updated to 12 months for Medicaid/HIM for maintenance therapy

Crohn's disease coverage: Member has Crohn's disease indication with documented therapeutic benefit timelines; dosing 300 mg IV every 4 weeks; discontinue if no therapeutic benefit by 12 weeks of induction or if unable to discontinue chronic concomitant steroids within six months of starting therapy; bypass of conventional therapies allowed if member has failed a biologic agent.12 weeks induction assessment

Initial approval durations extended to 12 months for CD; step therapy bypass rules may apply

Coverage is not authorized for primary progressive multiple sclerosis under this policy.

For Crohn's disease, Tysabri (natalizumab) and Tyruko (natalizumab‑sztn) must not be used in combination with immunosuppressants or TNFα inhibitors; concurrent use with these agents is contraindicated.

Coverage is excluded for patients who have or have had progressive multifocal leukoencephalopathy (PML) and for those with a history of hypersensitivity to Tysabri or Tyruko.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety per the applicable off‑label use policy (e.g., CP.CPA.09 for commercial, HIM.PA.154 for marketplace/ICHRA, CP.PMN.53 for Medicaid) or other evidence of coverage.

For Crohn's disease, continued therapy should be discontinued if the patient has not experienced therapeutic benefit by 12 weeks of induction therapy. The policy also notes discontinuation for patients unable to stop chronic concomitant steroids within six months of starting therapy.

Initial Therapy Requirements and Induction

inv-29: Initial therapy — Initial therapy criteria

Initial therapy — initial approval criteria

Initial MS: Diagnosis as specified (clinically isolated syndrome with failure/intolerance to interferon‑beta or glatiramer OR relapsing‑remitting MS with required prior therapies failed OR highly active MS with fingolimod failure OR secondary progressive MS); prescriber is or consulted neurologist; age ≥ 18; not concurrent with other MS DMTs; dose ≤ 300 mg every 4 weeks.

Prior authorization required for all disease modifying therapies for MS; Illinois HIM step therapy carve‑outs noted (IL HB 5395).

Initial CD (Medicaid): Diagnosis of Crohn's disease; prescriber is or consulted gastroenterologist; age ≥ 18; required prior trials of immunomodulators and specified biologics (adalimumab product ≥3 months or history of two TNF failures, and ustekinumab trial ≥3 months) unless contraindicated; not concurrent with immunosuppressants or TNFα inhibitors; dose ≤ 300 mg every 4 weeks.

Prior authorization required for some comparator biologics; see policy appendices.

inv-30: Initial therapy — Initial dosing and induction expectations

Continuation and Renewal Requirements

inv-31: Continuation therapy — Continuation therapy requirements

Continuation therapy — requirements for renewal/continuation

Continuation Therapy (general): Member must be currently receiving medication via Centene benefit or have previously met initial approval criteria (or be in a continuity‑of‑care situation); member must be responding positively to therapy; therapy must not be concurrent with disallowed agents for the indication (other MS DMTs for MS; immunosuppressants or TNFα inhibitors for CD); if dose increase requested, new dose must not exceed 300 mg (1 vial) every 4 weeks.

Approval durations: Medicaid/HIM/ICHRA 12 months; Commercial 6 months or to member renewal date

inv-32: Continued therapy for MS — Continuation/renewal requirements and duration for maintenance therapy

Continued therapy for MS — renewal requirements and maintenance duration

MS continuation: Member has documented continued benefit and remains enrolled in REMS; previous requirements for baseline relapses/EDSS and specific measures of positive response were removed; standard renewal durations updated to 12 months for Medicaid/HIM and remain 6 months for Commercial (or to member renewal date).

Step Therapy and Bypass Provisions

Indication	Required prior trials / step therapy	Notes
Multiple sclerosis (Relapsing forms; clinically isolated syndrome; secondary progressive)	Prior trial and failure/intolerance of specified oral DMTs or injectable interferon/glatiramer: dimethyl fumarate, teriflunomide, fingolimod, and an interferon‑beta agent or glatiramer — or failure of fingolimod for highly active MS; trials at up to maximally indicated doses unless contraindicated or adverse effects noted.	Prescriber must be neurologist or consult; not concurrent with other MS DMTs; dose ≤ 300 mg IV every 4 weeks. Illinois HIM step therapy carve‑outs noted (IL HB 5395).
Crohn's disease (Medicaid only)	Failure of ≥3 month trial of at least one immunomodulator (azathioprine, 6‑MP, methotrexate) unless contraindicated OR medical justification for inability; plus failure of one adalimumab product (≥3 months) or history of failure of two TNF blockers; failure of a ≥3 month trial of one ustekinumab product unless contraindicated.	Not to be used concurrently with immunosuppressants or TNFα inhibitors; dose ≤ 300 mg IV every 4 weeks. Prior authorization required; policy allows bypass of conventional therapies if member has failed a biologic agent (see CD-specific updates).

Context	Bypass / updated TNFi provision	Notes
Crohn's disease — step therapy and biologic sequence	Policy was updated to allow bypass of conventional (immunomodulator) therapies if the member has failed a biologic agent.	Also includes prior requirement of failure of one adalimumab product (≥3 months) or history of failure of two TNF blockers; ustekinumab trial required unless contraindicated. Approval duration: 12 months (Medicaid).
TNF‑inhibitor (TNFi) criteria	TNFi criteria were clarified to allow bypass when the member's history documents failure of two TNF blockers (history-based bypass provision).	Prior authorization applies to adalimumab products; Illinois HIM exceptions per IL HB 5395 apply.

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for use of natalizumab (Tysabri) and natalizumab-sztn (Tyruko). Providers must obtain PA before initiation and for continuation as required by the member's line of business.

Prior authorization required for natalizumab (J2323) and natalizumab-sztn (Q5134)
PA required for all disease-modifying therapies for MS
Approval durations: Medicaid/HIM/ICHRA — 12 months; Commercial — 6 months or to member renewal date, whichever is longer; Crohn’s Disease (Medicaid) — 12 months

Documentation Required

Documentation Requirement

Provider must submit clinical documentation supporting that the member meets all approval criteria. Failure to submit required documentation may result in denial of the request.

Billing Codes, Dose Limits, and Quantity Limits

Policy identifiermixed

CP.PHAR.259

Policy reference number (document identifier)

HCPCS CodesHCPCS

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

inv-14: Maximum single dose — 300 mg every 4 weeks

Maximum single dose300 mg (1 vial) every 4 weeks

Dose limit applies to initial and continued therapyDose must not exceed 300 mg every 4 weeks for initial and continuation approvals

Dose change restrictionIf request is for a dose increase, the new dose must not exceed 300 mg (1 vial) every 4 weeks

inv-15: Therapeutic benefit assessment in CD — No therapeutic benefit by 12 weeks of induction = discontinue

Therapeutic benefit assessment (Crohn's Disease)Discontinue if patient has not experienced therapeutic benefit by 12 weeks of induction therapy

Induction evaluation context

Dose and Quantity Limit Specifications

inv-35: natalizumab / natalizumab‑sztn — 300 mg

ProductNatalizumab (Tysabri) — single-use vial: 300 mg/15 mL

Standard dose300 mg IV every 4 weeks

Administration routeIntravenous infusion

inv-36: natalizumab / natalizumab-sztn — 300 mg

Product (biosimilar)Natalizumab‑sztn (Tyruko) — single-use vial: 300 mg/15 mL

Standard dose300 mg IV every 4 weeks (same dosing as reference product)

Route of administration

Administration and Facility Guidance

Note

Infusion center administration

Administer natalizumab/Tyruko only in an appropriate infusion setting; the product is supplied as an IV infusion and should be given at an infusion center per standard infusion practices.

Dosing regimen is IV administration of 300 mg every 4 weeks; product vial is 300 mg/15 mL.

Billing Rule

IV administration and vial details

Ensure IV administration per dosing instructions: natalizumab is given intravenously (300 mg every 4 weeks) and vial/dosing details are provided in the policy; site-specific restrictions are not specified beyond standard infusion settings.

Product availability: single‑use vial 300 mg/15 mL.
Policy notes administration is IV with dosing/vial information; no additional site‑specific limitations provided.

Biosimilar Inclusion and Billing

Note

Tysabri and Tyruko subject to same criteria

When requesting coverage, indicate whether the request is for the reference product Tysabri or the biosimilar Tyruko — both products are covered under the same clinical criteria.

Policy states Tysabri and Tyruko are integrin receptor antagonists and are subject to the same coverage criteria.

Billing Rule

Use HCPCS code Q5134 for Tyruko

If billing for the biosimilar, use the biosimilar‑specific HCPCS code Q5134 (natalizumab‑sztn); the policy was updated to add Q5134 and remove nonspecific codes previously used.

Coding update: HCPCS Q5134 added for natalizumab‑sztn (Tyruko); J3490 and C9399 were removed per coding revision notes.

Definitions and Safety Programs

inv-25: Natalizumab / natalizumab‑sztn — Integrin receptor antagonists; Tysabri (natalizumab) and Tyruko (natalizumab‑sztn) — used as monotherapy for relapsing forms of MS and fo...

Drug classIntegrin receptor antagonists (alpha-4 integrin inhibitor)

Products coveredTysabri (natalizumab) and Tyruko (natalizumab‑sztn)

IndicationsMonotherapy for relapsing forms of multiple sclerosis; induction and maintenance for moderately to severely active Crohn's disease (with prior therapy failures)

inv-26: Limitation of use - PML risk — Treatment increases risk of progressive multifocal leukoencephalopathy; clinicians should weigh benefits against this risk when initiatin...

Limitation of useTreatment increases risk of progressive multifocal leukoencephalopathy (PML); weigh benefits against risk when initiating or continuing therapy

Combination therapy warning (CD)

Background and Drug Information

Natalizumab (Tysabri) and its biosimilar natalizumab‑sztn (Tyruko) are alpha‑4 integrin receptor antagonists indicated as monotherapy for relapsing forms of multiple sclerosis and, in adults, for induction and maintenance of response in moderately to severely active Crohn's disease after inadequate response or intolerance to conventional therapies and TNF‑α inhibitors. Both agents carry a risk of progressive multifocal leukoencephalopathy (PML) and are available only through the required TOUCH® REMS program; clinicians should weigh benefits against PML risk when initiating or continuing therapy.

Policy Revision History

2024-02-22coding

Added HCPCS code Q5134 for natalizumab-sztn (Tyruko) and removed nonspecific HCPCS codes J3490 and C9399.

2025-02-12criteria_clarification

For MS continued therapy, removed requirements for documentation of baseline relapses/EDSS and specific measures of positive response; simplified renewal documentation and standardized HIM/Medicaid approval duration to 12 months.

2025-09-08coverage_change

OpenPayer

Natalizumab (Tysabri) and natalizumab‑sztn (Tyruko) coverage