Medical_Policy

Mountain State Medical Policy Bulletin

Section:	Injections
Number:	I-85
Topic:	Natalizumab (Tysabri®)
Effective Date:	September 1, 2008
Issued Date:	September 1, 2008
Date Last Reviewed:	08/2008

General Policy Guidelines

Indications and Limitations of Coverage

Natalizumab (Tysabri® ) is eligible for patients who meet the following criteria:

Multiple Sclerosis
For the treatment of patients with relapsing forms of multiple sclerosis to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations. The safety and efficacy of natalizumab beyond two years are unknown.

Members must have a documented diagnosis of relapsing-remitting or relapsing secondary progressive multiple sclerosis (340); and

Members initiating therapy for the first time must have at least one clinical relapse documented (e.g., functional disability, hospitalization, acute steroid therapy, etc.) during the prior year; and natalizumab is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies.

Natalizumab is not approved for combination therapy with interferons or copaxone.

Coverage will be limited to one 300 mg intravenous infusion every four weeks.

Because natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Natalizumab is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies.

Natalizumab has not been studied in patients with severe, disabling multiple sclerosis. The two main studies that appear in the FDA approved labeling only evaluated patients who had mild to moderate disability (Kurtzke Expanded Disability Status Scale scores between 0 and 5.0).

Refer to the Text Attachment below for scale.

Crohn's Disease
Inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's disease (555.0, 555.1, 555.2, 555.9) with evidence of inflammation who have had an inadequate response to, or are unable to tolerate conventional Crohn's disease therapies and inhibitors of TNF-α.

Per prescribing information, moderate to severely active Crohn's disease is defined as ≥ 220 and ≤ 450 per the Crohn's Disease Activity Index. Refer to the Text Attachment below for index.

Natalizumab should not be used in combination with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α (e.g., adalimumab, infliximab). Aminosalicylates may be continued during treatment with natalizumab.

Coverage will be limited to one 300 mg intravenous infusion every four weeks.

If the patient with Crohn's disease has not experienced therapeutic benefit by 12 weeks of induction therapy, discontinue natalizumab. For patients with Crohn's disease that start natalizumab while on chronic oral corticosteroids, commence steroid tapering as soon as a therapeutic benefit of natalizumab has occurred; if the patient with Crohn's disease cannot be tapered off to oral corticosteroids within six months of starting natalizumab, discontinue natalizumab.

Other than the initial six-month taper, prescribers should consider discontinuing natalizumab for patients who require additional steroid use that exceeds three months in a calendar year to control their Crohn's disease.

Natalizumab is not approved for use in patients under age 18.

Natalizumab is available only through a special restricted distribution program called the TOUCH™ Prescribing Program. Natalizumab must be administered only to multiple sclerosis patients registered in the MS TOUCH™ Prescribing Program and Crohn's disease patients registered in the CD TOUCH™ Prescribing Program.

The use of natalizumab for any other indication not listed in the coverage criteria above is considered experimental/investigational, and therefore, not covered. A participating, preferred, or network provider can bill the member for the denied service.

Coverage for natalizumab is determined according to individual or group customer benefits. Natalizumab is not reimbursable under the prescription drug benefit.

Description

Natalizumab (Tysabri) is a recombinant humanized IgG4_k monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity determining regions of a murine antibody that binds to a 4-integrin.

NOTE:: This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Procedure Codes

J2323

Traditional Guidelines

Refer to General Policy Guidelines

FEP Guidelines

Under the Federal Employee Program, all services that utilize FDA-approved drugs, devices, or biological products are eligible when intended for the treatment of a serious life-threatening condition and when medically necessary and appropriate for the patient’s condition.

PPO Guidelines

Refer to General Policy Guidelines

Managed Care POS Guidelines

Refer to General Policy Guidelines

Publications

References

Development of a Crohn's Disease Activity Index, National Cooperative Crohn's Disease Study. Gastroenterology, Vol. 70, No. 3, 03/1976

Rating Neurologic Impairment in Multiple Sclerosis: An Expanded Disability Status Scale (EDSS), Neurology, Vol. 33, No. 11, 11/1983

A Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis, The New England Journal of Medicine, Vol. 348, No. 1, 01/2003

US Food and Drug Administration (FDA). FDA issues public health advisory on Tysabri, a new drug for MS. FDA News. Rockville, MD: FDA; February 28, 2005

Progressive Multifocal Leukoencephalopathy After Natalizumab Therapy for Crohn's Disease, The New England Journal of Medicine, Vol. 353, No. 4, 07/2005

Progressive Multifocal Leukoencephalopathy Complicating Treatment with Natalizumab and Interferon Beta -1a for Multiple Sclerosis, The New England Journal of Medicine, Vol. 353, No. 4, 07/2005

Progressive Multifocal Leukoencephalopathy in a Patient Treated with Natalizumab, The New England Journal of Medicine, Vol. 353, No. 4, 07/2005

Progressive Multifocal Leukoencephalopathy and Natalizumab - Unforeseen Consequences, The New England Journal of Medicine, Vol. 353, No. 4, 07/2005

Natalizumab and Progressive Multifocal Leukoencephalopathy, The New England Journal of Medicine, Vol. 353, No. 4, 07/2005

Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy, The New England Journal of Medicine, Vol. 353, No. 4, 07/2005

Natalizumab Induction and Maintenance Therapy for Crohn's Disease, The New England Journal of Medicine, Vol. 353, No. 18, 11/2005

Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy, The New England Journal of Medicine, Vol. 354, No. 9, 03/2006

A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis, The New England Journal of Medicine, Vol. 354, No. 9, 03/2006

Natalizumab Plus Interferon Beta-1a for Relapsing Multiple Sclerosis, The New England Journal of Medicine, Vol. 354, No. 9, 03/2006

US Food and Drug Administration (FDA). FDA approves resumed marketing of Tysabri under a special distribution program. FDA News. Rockville, MD: FDA; June 5, 2006

Natalizumab Therapy for Moderate to Severe Crohn's Disease in Adolescents, Journal of Pediatric Gastroenterology and Nutrition: Vol. 44, No. 2, 02/2007

The Incidence and Significance of Anti-Natalizumab Antibodies, Neurology, Vol. 69, 2007

Natalizumab for the Treatment of Active Crohn's Disease: Results of the ENCORE Trial, Gastroenterology, Vol. 132, No. 5, 05/2007

Natalizumab for Multiple Sclerosis, The New England Journal of Medicine, Vol. 356, No. 25, 06/2007

US Food and Drug Administration (FDA). FDA approves Tysabri to treat moderate-to-severe Crohn's disease. FDA News. Rockville, MD: FDA; January 14, 2008

Elan Pharmaceuticals, Inc. Tysabri (natalizumab) injection for intravenous use. Prescribing Information. South San Francisco, CA, January 2008

FDA Issues Tysabri Warning www.fda.gov/medwatch/safety/2008/safety08/htm#Tysabri. Posted 02/28/2008

Melanoma Complicating Treatment with Natalizumab for Multiple Sclerosis, The New England Journal of Medicine, Vol. 358, No. 6, 02/2008

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Table Attachment

Text Attachment

Kurtzke Expanded Disability Status Scale (EDSS)

Rating	Status
0	Normal neurological exam
1.0	No disability, minimal symptoms
1.5	No disability, minimal signs in more than one area
2.0	Slightly more disability in one area
2.5	Slightly greater disability in two areas
3.0	Moderate disability in one area but still walking independently
3.5	Walking independently but with moderate disability in one area and more than minimal disability in several others
4.0	Walking without aid, self-sufficient, up and about some 12 hours a day despite relatively severe disability; able to walk without aid or rest some 500 meters
4.5	Walking without aid, up and about much of the day, able to work a full day, may have some limitation of full activity or require some help, relatively severe disability but able to walk without aid or rest some 300 meters
5.0	Walking without aid or rest for some 200 meters, disability severe enough to impair full daily activities, can work a full day without special provisions
5.5	Ambulatory without aid or rest for about 100 meters; disability severe enough to prevent full daily activities
6.0	Intermittent or unilateral constant assistance (cane, crutch, brace) required to walk about 100 meters with or without resting
6.5	Needs canes, crutches, braces to walk for 20 meters without resting
7.0	Unable to walk beyond five meters even with aid; mostly confined to a wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day
7.5	Unable to take more than a few steps; restricted to wheelchair; may need aid in transfer; wheels self but cannot carry on in standard wheelchair a full day; may require motorized wheelchair
8.0	Essentially restricted to bed, chair, or wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms
8.5	Essentially restricted to bed much of day; has some effective use of arms; retains some self-care functions
9.0	Helpless bed patient; can communicate and eat
9.5	Totally helpless bed patient; unable to communicate effectively or eat/swallow
10.0	Death due to MS

Crohn's Disease Activity Index (CDAI)

Clinical or laboratory variable	Weighting factor
Number of liquid or soft stools each day for seven days	x2
Abdominal pain (graded from 0-3 on severity) each day for seven days	x5
General well being, subjectively assessed from 0 (well) to 4 (terrible) each day for seven days	x7
Symptoms or findings presumed related to Crohn's disease* *One point each is added for each set of complications arthritis or arthralgia iritis or uveitis erythema nodosum, pyoderma gangrenosom, or aphthous stomatitis anal fissure, fistula, or perirectal abscess other bowel related fistula febrile (fever) episode over 100 degrees during past week	x20
Taking Lomitil or opiates for diarrhea	x30
Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite)	x10
Absolute deviation of hematocrit from 47% in men and 42% in women Hematocrit [(typical - current) x6] Normal average - for male = 47 for female = 42	x6
Percent deviation from standard weight 100 x [(standard weight - actual body weight)/standard weight]	x1

Procedure Code Attachments

Diagnosis Codes

Glossary

Term	Description
Disease-modifying antirheumatic drug (DMARD)	Medicines classified as disease-modifying antirheumatic drugs (DMARDS) have the potential to reduce or prevent joint damage and preserve joint integrity and function. Commonly used traditional DMARDs include but are not limited to leflunomide, sulfasalazine, hydroxychloroquine, azathioprine, and methotrexate.
Inhibitors of tumor necrosis factor alpha (TNF-α)	TNF-α inhibitors block the action of a protein in your body called tumor necrosis factor alpha (TNF-α). TNF-α is made by your body's immune system. People with certain diseases have too much TNF-α that can cause the immune system to attack normal healthy parts of the body (e.g., adalimumab [Humira®], infliximab[Remicade® ]).

Term

Description

Disease-modifying antirheumatic drug (DMARD)

Medicines classified as disease-modifying antirheumatic drugs (DMARDS) have the potential to reduce or prevent joint damage and preserve joint integrity and function.

Commonly used traditional DMARDs include but are not limited to leflunomide, sulfasalazine, hydroxychloroquine, azathioprine, and methotrexate.

Inhibitors of tumor necrosis factor alpha (TNF-α)

TNF-α inhibitors block the action of a protein in your body called tumor necrosis factor alpha (TNF-α). TNF-α is made by your body's immune system. People with certain diseases have too much TNF-α that can cause the immune system to attack normal healthy parts of the body (e.g., adalimumab [Humira®], infliximab[Remicade® ]).

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Medical policies are designed to supplement the terms of a member's contract. The member's contract defines the benefits available; therefore, medical policies should not be construed as overriding specific contract language. In the event of conflict, the contract shall govern.

Medical policies do not constitute medical advice, nor the practice of medicine. Rather, such policies are intended only to establish general guidelines for coverage and reimbursement under Mountain State Blue Cross Blue Shield plans. Application of a medical policy to determine coverage in an individual instance is not intended and shall not be construed to supercede the professional judgment of a treating provider. In all situations, the treating provider must use his/her professional judgment to provide care he/she believes to be in the best interest of the patient, and the provider and patient remain responsible for all treatment decisions.

Mountain State Blue Cross Blue Shield (MSBCBS) retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of MSBCBS. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.