CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Natalizumab (Tysabri/Tyruko) — Coverage Criteria

Defines prior authorization, documentation, prescriber specialty, and clinical criteria for coverage of Tysabri/Tyruko for Crohn's disease and relapsing forms of multiple sclerosis for members of the plan.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyNatalizumab (Tysabri/Tyruko) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization with required documentation and anti-JCV antibody testing before initiating therapy; authorization may be granted for 12 months.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 moauthorization duration

FDA + compendiacovered indications

Anti-JCVtesting required

GI / Neuroprescriber specialty

Coverage Criteria

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CD - Indication and prior therapy: Member is an adult with moderately to severely active Crohn's disease with evidence of inflammation who has had an inadequate response to, or is unable to tolerate, conventional Crohn's disease therapies and inhibitors of TNF-α

Matches FDA-approved indication; combination with immunosuppressants or TNF inhibitors is prohibited

Prior biologic therapy: Member has received any other biologic indicated for the treatment of moderately to severely active Crohn's disease (prior biologic or TNF-α inhibitor failure or intolerance)

Required prior to authorization per plan step-therapy

Anti-JCV antibody testing: Member has been tested for anti-JCV antibodies

Testing required prior to authorization due to PML risk

Authorization duration: Authorization may be granted for 12 months

Standard initial authorization duration; renewal requires documentation of response

Initial approval — MS/CIS

Covered for relapsing forms of MS or CIS when ALL of the following are met:

MS/CIS - Diagnosis: Member has a diagnosis of a relapsing form of multiple sclerosis (including relapsing-remitting and active secondary progressive disease) or clinically isolated syndrome

Indications reflect FDA-approved uses for monotherapy

Anti-JCV antibody testing: Member has been tested for anti-JCV antibodies

Testing required prior to authorization due to PML risk

Authorization duration and response: Authorization may be granted for 12 months and member must achieve or maintain disease stability or improvement

Continuation requires documentation of positive clinical response (disease stability or improvement)

Continuation therapy — Crohn's disease

Continuation approval for Crohn's disease when ALL of the following are met:

Documentation of response: Chart notes or medical record documentation support positive clinical response to therapy or remission

Examples include improvement in abdominal pain, diarrhea, body weight, abdominal mass, hematocrit, mucosal appearance on imaging/endoscopy, or disease activity scores (e.g., CDAI)

Authorization duration: Authorization may be granted for 12 months

Standard continuation duration

All indications beyond the FDA-approved uses and recognized compendial indications are considered experimental/investigational and not medically necessary. Natalizumab (Tysabri/Tyruko) is FDA-approved only for: (1) induction and maintenance of response and remission in adult patients with moderately to severely active Crohn's disease with evidence of inflammation after inadequate response or intolerance to conventional therapies and TNF-α inhibitors, and (2) as monotherapy for relapsing forms of multiple sclerosis (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease).

Natalizumab must not be used in combination with other immunosuppressive therapies. The FDA‑approved labeling and this policy prohibit concomitant use with immunosuppressants (e.g., 6‑mercaptopurine, azathioprine, cyclosporine, methotrexate) and with other disease‑modifying multiple sclerosis agents or TNF inhibitors. Concurrent use with these agents may result in a denial of the request.

Provider Actions & Prior Authorization

Prior Authorization

Prior authorization for Crohn's disease

Prior authorization required for adult members with moderately to severely active Crohn's disease who have had an inadequate response to, or intolerance of, conventional therapies and prior biologic/TNF‑α inhibitors. Authorization may be granted for up to 12 months when documentation shows the member has received any other biologic indicated for Crohn's disease and has been tested for anti‑JCV antibodies. Tysabri/Tyruko must not be used in combination with immunosuppressants or TNF inhibitors.

Authorization duration: 12 months
Prior biologic/TNF inhibitor failure or intolerance required
Anti‑JCV antibody testing required

Prior Authorization

Prior authorization for MS/CIS

Prior authorization required for relapsing forms of multiple sclerosis and clinically isolated syndrome (CIS). Authorization may be granted for up to 12 months for members diagnosed with relapsing MS (including relapsing‑remitting and active secondary progressive disease) or CIS when anti‑JCV antibody testing has been completed. Clinicians should weigh PML risk when initiating or continuing therapy.

Authorization duration: 12 months
Applies to relapsing MS (including relapsing‑remitting and active secondary progressive) and CIS
Anti‑JCV antibody testing required; assess PML risk

Denial Risk

Prohibited concomitant therapy

Concurrent use of the requested agent with other disease‑modifying MS therapies, immunosuppressants, or TNF inhibitors is prohibited and may lead to denial.

Do not combine with other DMTs (Ampyra and Nuedexta are NOT disease‑modifying)
Do not combine with immunosuppressants (e.g., 6‑mercaptopurine, azathioprine, cyclosporine, methotrexate)
Do not combine with TNF inhibitors (e.g., adalimumab, infliximab)

Documentation Required

Required documentation

Submit chart notes, medical record documentation, or claims history to support prior medication trials and responses for initial Crohn's disease requests. For continuation requests, submit chart notes or medical records demonstrating clinical response or remission (improvement in symptoms, weight, hematocrit, endoscopic/imaging findings, or disease activity score).

Initial requests: documentation of previous medications tried and response to therapy
Continuation requests: documentation of positive clinical response or maintained remission — examples include improvement in abdominal pain, diarrhea, body weight, abdominal mass, hematocrit, mucosal appearance on endoscopy/CTE/MRE/ultrasound, or CDAI score

Denial Risk

Prior biologic or TNF inhibitor failure

Approval for Crohn's disease requires prior inadequate response or intolerance to prior biologic therapy or TNF‑α inhibitors as part of the medical necessity determination.

Document prior biologic or TNF‑α inhibitor failure or intolerance in the medical record or claims history

Background

Natalizumab (Tysabri/Tyruko) is a monoclonal antibody indicated for two primary uses: (1) to induce and maintain clinical response and remission in adults with moderately to severely active Crohn's disease with evidence of inflammation who have had inadequate response to, or cannot tolerate, conventional therapies and TNF‑α inhibitors; and (2) as monotherapy for relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing‑remitting MS, and active secondary progressive disease. Treatment with natalizumab carries an increased risk of progressive multifocal leukoencephalopathy (PML), and anti‑JCV antibody testing is required prior to use to help assess that risk. Prior authorization, documentation of prior therapies, and specialty prescriber requirements apply as specified in the policy.

Definitions

Progressive multifocal leukoencephalopathy (PML) risk — definition and risk note

DefinitionProgressive multifocal leukoencephalopathy (PML) is a serious opportunistic brain infection associated with natalizumab (Tysabri/Tyruko) use.

Clinical significanceTreatment with Tysabri or Tyruko increases the risk of PML; clinicians must weigh expected benefit against this risk when initiating or continuing therapy.

Risk mitigationPhysicians should consider the PML risk in treatment decisions and avoid combining Tysabri/Tyruko with immunosuppressants or TNF‑α inhibitors, which are contraindicated in combination.

Implication for coverageAnti‑JCV antibody testing is required prior to authorization to assess PML risk (testing requirement referenced in coverage criteria).