Subject: Tysabri-Tyruko SGM 1846-A P2025a

Drug

TYSABRI  (natalizumab)

TYRUKO  (natalizumab-sztn)

Policy:

Indications

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications^1,2

• Inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn’s disease (CD) with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of tumor necrosis factor alpha (TNF-α). Tysabri and Tyruko should not be used in combination with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α.
• Monotherapy for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Tysabri and Tyruko increase the risk of progressive multifocal leukoencephalopathy (PML). When initiating and continuing treatment with Tysabri or Tyruko, physicians should consider whether the expected benefit of Tysabri or Tyruko is sufficient to offset this risk.

All other indications are considered experimental/investigational and not medically necessary.

Documentation

Submission of the following information is necessary to initiate the prior authorization review:

Crohn’s Disease (CD)

Initial Requests

Chart notes, medical record documentation, or claims history supporting previous medications tried, including response to therapy.

Continuation Requests

Chart notes or medical record documentation supporting positive clinical response to therapy or remission.

Prescriber Specialties

This medication must be prescribed by or in consultation with one of the following:

• Crohn’s disease: gastroenterologist
• Multiple sclerosis: neurologist

Coverage Criteria

Crohn’s Disease (CD)^1-5

Authorization of 12 months may be granted for adult members who have received any other biologic indicated for the treatment of moderately to severely active Crohn’s disease and who have been tested for anti-John Cunningham virus (JCV) antibodies.

Relapsing Forms of Multiple Sclerosis (MS)^1,2

Authorization of 12 months may be granted to members who have been diagnosed with a relapsing form of multiple sclerosis (including relapsing-remitting and secondary progressive disease for those who continue to experience relapse) and who have been tested for anti-JCV antibodies.

Clinically Isolated Syndrome^1,2

Authorization of 12 months may be granted for treatment of clinically isolated syndrome of multiple sclerosis when the member has been tested for anti-JCV antibodies.

Continuation of Therapy

Crohn’s Disease (CD)^1-3,5

Authorization of 12 months may be granted for all adult members (including new members) who are using the requested medication for moderately to severely active Crohn’s disease and who achieve or maintain remission.

Authorization of 12 months may be granted for all adult members (including new members) who are using the requested medication for moderately to severely active Crohn’s disease and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:

• Abdominal pain or tenderness
• Diarrhea
• Body weight
• Abdominal mass
• Hematocrit
• Appearance of the mucosa on endoscopy, computed tomography enterography (CTE), magnetic resonance enterography (MRE), or intestinal ultrasound
• Improvement on a disease activity scoring tool (e.g., Crohn’s Disease Activity Index [CDAI] score)

Relapsing Forms of Multiple Sclerosis (MS) or Clinically Isolated Syndrome^1,2

Authorization of 12 months may be granted for all members (including new members) who achieve or maintain a positive clinical response as evidenced by experiencing disease stability or improvement while receiving the requested medication.

Other

For all indications: Members cannot use the requested medication concomitantly with any other disease modifying multiple sclerosis agents (Note: Ampyra and Nuedexta are not disease modifying), immunosuppressants, or tumor necrosis factor (TNF) inhibitors (e.g., adalimumab, infliximab).

Dosage and Administration

Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines.

Place of Service:

Outpatient

The above policy is based on the following references:

1. Tysabri [package insert]. Cambridge, MA: Biogen Inc.; March 2025.
2. Tyruko [package insert]. Princeton, NJ: Sandoz Inc.; August 2023.
3. Talley NJ, Abreu MT, Achkar J, et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011;106(Suppl 1):S2-S25.
4. Lichtenstein GR, Loftus EV, Afzali A, et al. ACG Clinical Guideline: Management of Crohn’s Disease in Adults. Am J Gastroenterol. 2025;120(6):1225-1264.
5. Feuerstein JD, Ho EY, Shmidt E, et al. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn’s Disease. Gastroenterology. 2021;160:2496-2508.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

February 15, 2026