64406-0008 - Tysabri 300 MG/15 ML CONC (BIOGEN IDEC)
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.
Natalizumab for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.
Natalizumab for the treatment of other conditions/diseases is considered investigational.
Natalizumab is considered medically appropriate if ALL of the following criteria are met:
Individual is 18 years of age or older
Prescriber and patient must be enrolled in and meet the conditions of the TOUCH program
Documented negative JCV antibody ELISA test within the past 6 months**
Not used in combination with antineoplastic, immunosuppressant, or immunomodulating agents
Individual must not have a systemic medical condition resulting in significantly compromised immune system function
Diagnosis of ANY ONE of the following:
Multiple sclerosis (MS) if ALL the following
Confirmed diagnosis of MS as documented by laboratory report (i.e. MRI, unless contraindicated)
The agent is used as monotherapy
Definitive diagnosis of Multiple Sclerosis with a relapsing-remitting form of Multiple Sclerosis, e.g., relapsing-remitting disease (RRMS) or secondary progressive MS (SPMS) with relapses based upon ALL of the following:
Dissemination in time (Development/appearance of new CNS lesions over time) and ANY ONE of the following:
> 2 clinical attacks
1 clinical attack and ANY 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
Dissemination in space (Development of lesions in distinct anatomical locations within the CNS; multifocal) and ANY ONE of the following:
> 2 lesions
1 lesion and ANY 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)
Crohn’s disease (CD) if ALL the following:
The agent is used as monotherapy (not used concurrently with another biologic drug or immunosuppressants [e.g., 6-mercaptopurine, azathioprine cyclosporine, methotrexate, etc. used for Crohn’s Disease)
Disease is moderately- to severely-active
Physician has assessed baseline disease severity utilizing an objective measure/tool
Documented trial and failure on ONE oral immunosuppressive therapy for at least 3 months, unless use is contraindicated, such as corticosteroids, methotrexate, azathioprine, and/or 6- mercaptopurine
Documented trial and failure on ONE TNF-alpha inhibitor for at least 3 months, unless contraindicated, such as (e.g., infliximab, certolizumab, adalimumab)
|** Risk factors for the development of Progressive Multifocal Leukoencephalopathy (PML)|
|*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.|
Natalizumab considered medically appropriate for renewal if ALL of the following criteria are met:
Individual continues to meet initial approval criteria
Absence of unacceptable toxicity from the drug such as hypersensitivity reactions; hepatotoxicity; signs or symptoms of progressive multifocal leukoencephalopathy (PML ); development of severe infections (including pneumonias, pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, herpes, urinary tract infections, gastroenteritis, vaginitis, tonsillitis, meningitis) etc.
Documented negative JCV antibody ELISA test within the past 6 months
Diagnosis of ANY ONE of the following:
Multiple Sclerosis continuous monitoring of response to therapy (manifestations of MS disease activity include, but are not limited to, an increase in annualized relapse rate (ARR), development of new/worsening T2 hyperintensities or enhancing lesions on brain/spinal MRI, and progression of sustained impairment as evidenced by expanded disability status scale (EDSS), timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT)
Inadequate response, in those who have been adherent and receiving therapy for sufficient time to realize the full treatment effect, is defined as >1 relapse, > 2 unequivocally new MRI-detected lesions, or increased disability on examination over a one-year period
Infusion reactions or breakthrough disease activity may indicate neutralizing natalizumab antibodies. Therapy should be discontinued in patients who have persistent neutralizing antibodies to natalizumab
Crohn’s Disease if ANY ONE of the following:
Initial renewal only if ALL of the following:
Clinical response and remission of disease is seen by 12 weeks
Second renewal only if ALL of the following:
Individual has been tapered off of oral corticosteroids within six months of starting natalizumab
Disease response as indicated by improvement in signs and symptoms compared to baseline such as endoscopic activity, number of liquid stools, presence and severity of abdominal pain, presence of abdominal mass, body weight compared to IBW, hematocrit, presence of extra intestinal complications, tapering or discontinuation of corticosteroid therapy, use of anti-diarrheal drugs, and/or an improvement on a disease activity scoring tool [e.g. an improvement on the Crohn’s Disease Activity Index (CDAI) score or the Harvey-Bradshaw Index score.]
All subsequent renewals if ALL of the following:
Individual does not require additional steroid use that exceeds three months in a calendar year to control their Crohn’s disease
as indicated by improvement in signs and symptoms
compared to baseline such as endoscopic activity,
number of liquid stools, presence and severity of
abdominal pain, presence of abdominal mass, body weight
compared to IBW, hematocrit, presence of extra intestinal
or discontinuation of corticosteroid therapy,
use of anti-diarrheal drugs, and/or an improvement
on a disease activity scoring tool [e.g. an improvement
on the Crohn’s Disease Activity Index (CDAI) score
or the Harvey-Bradshaw Index score.]
DOSAGE & ADMINISTRATION
300 mg intravenous infusion over one hour every four weeks
LENGTH OF AUTHORIZATION
Coverage is eligible for renewal
Initial coverage will be provided for 12 weeks
Renewal coverage will be provided for 6 months
Coverage will be provided for 6 months and is eligible for renewal.
Refer to DOSAGE LIMITS below
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.
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.
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).
Lexi-Comp Online. (2018). AHFS DI. Natalizumab. Retrieved November 5, 2018 from Lexi-Comp Online with AHFS.
Lichtenstein GR, Loftus EV, Isaacs KI, 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. (2018, September). Natalizumab. Retrieved November 5, 2018 from MICROMEDEX Healthcare Series.
Rae-Grant, A, Day GS, Marrie RA, et al. 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® 2018;90:777-788. doi:10.1212/WNL.0000000000005347.
Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2.
U. S. Food and Drug Administration. (2018, April). Center for Drug Evaluation and Research. Tysabri® (natalizumab). Retrieved November 5, 2018 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125104s953s955lbl.pdf.
ORIGINAL EFFECTIVE DATE: 1/13/2007
MOST RECENT REVIEW DATE: 3/2/2019
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.
Maximum billable units per dose and over time by indication as a Medical Benefit 1 billable unit = 1mg