BlueCross BlueShield of Tennessee Medical Policy Manual

Natalizumab

NDC CODE(S)

64406-0008-XX TYSABRI 300MG/15ML Solution (BIOGEN IDEC)

DESCRIPTION

Natalizumab is a recombinant humanized IgG4κ monoclonal antibody produced in murine myeloma cells. It was the first member of a class of monoclonal antibodies referred to as selective adhesion molecule inhibitors. Natalizumab binds to the surface alpha-4 integrin receptor sites of all leukocytes except neutrophils, inhibiting the adhesion of leukocytes to their counter-receptors found on activated vascular endothelium cells and vascular endothelial cells of the gastrointestinal tract.  This prevents leukocytes from migrating across the endothelium into inflamed parenchymal tissue where they exacerbate the inflammatory process.

Additionally, natalizumab interferes with movement of potentially damaging immune cells across the blood-brain-barrier and into the brain and spinal cord.  It also likely inhibits further recruitment and inflammatory activity of activated immune cells. 

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

 

 

*Definitive diagnosis of MS with a relapsing-remitting course is based upon BOTH dissemination in time and space. Unless contraindicated, MRI should be obtained (even if criteria are met).

 

Dissemination in time

(Development/appearance of new CNS lesions over time)

Dissemination in space

(Development of lesions in distinct anatomical locations within the CNS; multifocal)

 

·         ≥ 2 clinical attacks; OR

·         1 clinical attack AND one of the following:

  • MRI indicating simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time or by a new T2- hyperintense or gadolinium-enhancing lesion on follow-up MRI compared to baseline scan

  • CSF-specific oligoclonal bands

·         ≥ 2 lesions; OR

·         1 lesion AND one of the following:

  • Clear-cut historical evidence of a previous attack involving a lesion in a distinct anatomical location

  •  MRI indicating ≥ 1 T2-hyperintense lesions characteristic of MS in ≥ 2 of 4 areas of the CNS (periventricular, cortical or juxtacortical,  infratentorial, or spinal cord)

 

**Active secondary progressive MS (SPMS) is defined as the following:

 

·         Expanded Disability Status Scale (EDSS) score > 3.0; AND

  • Disease is progressive ≥ 3 months following an initial relapsing-remitting course (i.e., EDSS score increase by 1.0 in patients with EDSS ≤5.5 or increase by 0.5 in patients with EDSS ≥6) AND

  • ≥ 1 relapse within the previous 2 years; OR

  • Patient has gadolinium-enhancing activity or new and unequivocally enlarging T2 contrast enhancing lesions as evidenced by MRI

 

***Definitive diagnosis of CIS is based upon ALL of the following:

 

·         A monophasic clinical episode with patient-reported symptoms and objective findings reflecting a focal or multifocal inflammatory demyelinating event in the CNS

·         Neurologic symptom duration of at least 24 hours, with or without recovery

·         Absence of fever or infection

·         Patient is not known to have multiple sclerosis

  ****Risk factors for the development of Progressive Multifocal Leukoencephalopathy (PML)

 

·         Presence of anti-JCV antibodies. Patients who are anti-JCV antibody positive have a higher risk for developing PML.

·         Prior treatment with an immunosuppressant (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil)

·         Longer treatment duration, especially beyond 2 years

·         Elevated levels of anti-JCV antibody response index (i.e., index > 0.9)

  • In those using natalizumab for 25–36 months with no prior use of immunosuppressants, the PML risk is 0.2 per 1,000 in those with an index of 0.9 or less, 0.3 per 1,000 in those with an index of 0.9–1.5, and 3 per 1,000 in those with an index greater than 1.5.

 

Anti-JCV

Antibody

Negative

TYSABRI

Exposure (months)

Anti-JCV Antibody Positive

No Prior Immunosuppressant Use

Prior Immunosuppressant Use

 

 

1/10,000

1-24

<1/1,000

1/1,000

25-48

2/1,000

6/1,000

49-72

4/1,000

7/1,000

73-96

2/1,000

6/1,000

Note:requirements for JCV negativity are based upon recommendations from current guidelines. Use in patients who are anti-JCV antibody positive will be reviewed on a case-by-case basis.

RENEWAL CRITERIA

INDICATION(S)

DOSAGE & ADMINISTRATION

All Indications

Administer 300 mg intravenous infusion over one hour every four weeks

LENGTH OF AUTHORIZATION

Crohn’s Disease:

Multiple Sclerosis:

Refer to DOSAGE LIMITS below

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

Lexi-Comp Online. (2020, March). AHFS DI. Natalizumab. Retrieved October 12, 2020 from Lexi-Comp Online with AHFS.

Lichtenstein G. R., Loftus E. V., Isaacs K.I, et al. ACG Clinical Guideline: Management of Crohn’s Disease in Adults. Am J Gastroenterol 2018; 113:481–517; doi: 10.1038/ajg.2018.27.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2020, August). Natalizumab. Retrieved October 12, 2020 from MICROMEDEX Healthcare Series.

Rae-Grant, A., Day G. S., Marrie R. A., et al.  (2018) Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology® 90:777-788. doi:10.1212/WNL.0000000000005347.

Thompson A. J., Banwell B. L., Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb; 17 (2):162-173. Retrieved September 18, 2019 doi: 10.1016/S1474-4422(17)30470-2.

U. S. Food and Drug Administration. (2020, June). Center for Drug Evaluation and Research. Tysabri® (natalizumab). Retrieved October 12, 2020 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125104s953s955lbl.pdf.

ORIGINAL EFFECTIVE DATE:  1/13/2007

MOST RECENT REVIEW DATE:   3/2/2021

ID_MRx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information

 

DOSAGE LIMITS

Maximum billable units per dose and over time by indication as a Medical Benefit   

DIAGNOSIS

BILLABLE UNIT

MAXIMUM UNITS

All indications

1 billable unit = 1mg

300 billable units every 28 days