Natalizumab (Tysabri®) Notification

• Natalizumab (Tysabri®) intravenous infusion for administration by a healthcare professional 

• As monotherapy, for treatment of adults with relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease 
  • Limitations of use: Natalizumab increases risk of progressive multifocal leukoencephalopathy (PML). When initiating and continuing natalizumab treatment, consideration should be taken whether expected benefit is sufficient to offset risk. 
• For inducing and maintaining clinical response and remission in adults 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 TNF-alpha inhibitors 
  • Limitations of use: Not for use in combination with immunosuppressants or TNF-alpha inhibitors

The restricted product(s) may be considered medically necessary when the following criteria are met:

Initial Criteria for Approval:

1. The patient has a diagnosis of a relapsing form of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, or active secondary progressive disease; AND 
   1. The patient is 18 years of age or older; AND
   2. The patient must still either be able to walk at least a few steps with or without aid, or alternatively must have some functional arm/ hand use consistent with performing activities of daily living; AND
   3. ONE of the following:
      1. The patient has highly active MS disease activity AND BOTH of the following [medical record documentation required]: 
         1. The patient has greater than or equal to 2 relapses in the previous year; AND 
         2. ONE of the following: 
            1. The patient has greater than or equal to 1 gadolinium enhancing lesion on MRI; OR 
            2. The patient has a significant increase in T2 lesion load compared with a previous MRI; OR
      2. ONE of the following:
         1. The patient has tried and had an inadequate response to ONE of the following: dimethyl fumarate (generic Tecfidera), fingolimod (generic Gilenya), glatiramer acetate (generic Copaxone), or teriflunomide (generic Aubagio) [medical record documentation required]; OR 
         2. The patient has an intolerance or hypersensitivity to ONE of the following: dimethyl fumarate (generic Tecfidera), fingolimod (generic Gilenya), glatiramer acetate (generic Copaxone), or teriflunomide (generic Aubagio) [medical record documentation required]; OR 
         3. The patient has an FDA labeled contraindication to ALL of the following: dimethyl fumarate (generic Tecfidera), fingolimod (generic Gilenya), glatiramer acetate (generic Copaxone), and teriflunomide (generic Aubagio) [medical record documentation required]; OR
      3. The patient has been treated with at least three MS agents from different drug classes (see “MS Disease Modifying Agents drug classes” table below) [medical record documentation required]; AND
   4. The patient is NOT receiving the requested agent in combination with two or more disease-modifying drugs for multiple sclerosis, including glatiramer (Copaxone, Glatopa), interferon beta-1b (Betaseron, Extavia), interferon beta-1a (Avonex, Rebif), peginterferon beta-1a (Plegridy), fingolimod (Gilenya, Tascenso ODT), teriflunomide (Aubagio), dimethyl fumarate (Tecfidera), monomethyl fumarate (Bafiertam), ofatumumab (Kesimpta), alemtuzumab (Lemtrada), siponimod (Mayzent), cladridine (Mavenclad), ocrelizumab (Ocrevus), ponesimod (Ponvory), natalizumab (Tysabri), diroximel fumarate (Vumerity), ozanimod (Zeposia), and ublituximab-xiiy (Briumvi); OR
2. The patient has a diagnosis of moderately to severely active Crohn’s disease (CD); AND
   1. The patient is 18 years of age or older; AND
   2. ONE of the following:
      1. The patient has tried and had an inadequate response to at least ONE conventional agent (i.e., 6-mercaptopurine, azathioprine, corticosteroids [e.g., prednisone, budesonide EC capsule], methotrexate) used in the treatment of CD for at least 3-months [medical record documentation required]; OR
      2. The patient has an intolerance or hypersensitivity to ONE of the conventional agents used in the treatment of CD [medical record documentation required]; OR
      3. The patient has an FDA labeled contraindication to ALL of the conventional agents used in the treatment of CD [medical record documentation required]; AND 
   3. ONE of the following:
      1. The patient has tried and had an inadequate response to at least ONE of the following biologic agents for the treatment of CD used for at least 3 months: Cimzia® (certolizumab pegol), Humira® (adalimumab), Remicade® (infliximab), Skyrizi (risankizumab), Stelara® (ustekinumab) [medical record documentation required]; OR
      2. The patient has an intolerance or hypersensitivity to at least ONE biologic agent for the treatment of CD [medical record documentation required]; OR
      3. The patient has an FDA labeled contraindication to ALL biologic agents for the treatment of CD [medical record documentation required]; AND
   4. The patient is NOT receiving the requested agent in combination with an immunomodulatory agent (e.g., TNF-alpha inhibitors, JAK inhibitors, IL-4 inhibitors) for CD; AND 
   5. The patient is NOT receiving the requested agent in combination with another immunosuppressant agent (e.g., 6-mercaptopurine, azathioprine, cyclosporine, methotrexate); AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist for CD, neurologist for MS), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis; AND 
4. The prescriber is registered through the MS TOUCH® or CD TOUCH® Prescribing Program(s); AND
5. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
6. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)

Continuation Criteria for Approval:

1. The patient was approved through Blue Cross NC initial criteria for approval; OR
2. The patient would have met initial criteria for approval at the time they started therapy; AND
3. The patient has had clinical benefit while receiving treatment with the requested agent (e.g., disease stability and/or improvement); AND 
4. ONE of the following:
   1. For multiple sclerosis (MS), the patient is NOT receiving the requested agent in combination with two or more disease-modifying drugs for MS, including glatiramer (Copaxone, Glatopa), interferon beta-1b (Betaseron, Extavia), interferon beta-1a (Avonex, Rebif), peginterferon beta-1a (Plegridy), fingolimod (Gilenya, Tascenso ODT), teriflunomide (Aubagio), dimethyl fumarate (Tecfidera), monomethyl fumarate (Bafiertam), ofatumumab (Kesimpta), alemtuzumab (Lemtrada), siponimod (Mayzent), cladridine (Mavenclad), ocrelizumab (Ocrevus), ponesimod (Ponvory), natalizumab (Tysabri), diroximel fumarate (Vumerity), ozanimod (Zeposia), and ublituximab-xiiy (Briumvi); OR
   2. For Crohn’s disease (CD), the patient will NOT be using the requested agent in combination with an immunomodulatory agent (e.g., TNF-alpha inhibitors, JAK inhibitors, IL-4 inhibitors) for CD; AND
5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist for CD, neurologist for MS), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis; AND 
6. The prescriber is registered through the MS TOUCH® or CD TOUCH® Prescribing Program(s); AND
7. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
8. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)

1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR 
2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met:
   1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR 
   2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR
   3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR 
   4. Re-initiation of therapy, defined as ONE of the following: 
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR 
   5. Requirement of a change in the requested restricted product formulation; AND 
3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.

All information referenced is from FDA package insert unless otherwise noted below.

1.  Bloomingren G, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012; 366:1870-1880.

 Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q4 annually.

July 2023: Criteria change: For MS: Adjusted requirement of trial and failure of alternative MS disease-modifying therapy to one generic product [dimethyl fumarate (generic Tecfidera), fingolimod (generic Gilenya), glatiramer acetate (generic Copaxone), or teriflunomide (generic Aubagio)] or previous treatment with at least 3 MS agents from different drug classes. Added requirement of some walking or functional arm/hand use within initial criteria. Removed requirement of no concomitant use with another chronic immunosuppressant agent for clarity. For CD: Updated list of conventional agents and biologic agents for trial and failure. For both indications, added continuation criteria and removed requirement of no significant immunocompromise. Adjusted policy formatting and added reference table with drug classes of MS disease modifying agents. Policy notification given 5/2/2023 for effective date 7/1/2023.

June 2021: Criteria change: CD: Medical record documentation required for trial and failure of conventional agents; removed criterion point regarding medication history indicating use of another biologic immunomodulator agent for the treatment of CD.

June 2021: Criteria change: CD: Addition of criteria for history of use of another biologic immunomodulator agent for the same indication; added requirements to be prescribed by or in consultation with a specialist; added maximum units; medical policy formatting change. Policy notification given 4/16/2021 for effective date 6/16/2021.

Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy.