gModa Health Plan, Inc.
Medical Necessity Criteria
Origination Date: 08/13
Developed By: Medical Criteria Committee
Approved:
Mary Engrav, MD
Subject: Tysabri (natalizumab)
Page 1 of 5
Revision Date(s): 12/2013, 12/2014,
04/2015, 10/2015, 02/2016
Effective Date: 10/1/2013
Date: 02/24/2016
Description:
Natalizumab is a recombinant humanized immunoglobulin G4-kappa monoclonal antibody produced in
murine myeloma cells. Natalizumab binds to the alpha-4 subunit of alpha-4 beta-1 and alpha-4 beta-7
integrins expressed on the surface of all leukocytes except neutrophils and inhibits the alpha-4–mediated
adhesion of leukocytes to their counter-receptor(s). The receptors for the alpha-4 family of integrins
include vascular cell adhesion molecule 1 (VCAM-1), which is expressed on activated vascular endothelium,
and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) present on vascular endothelial cells of the GI
tract. Disruption of these molecular interactions prevents transmigration of leukocytes across the
endothelium into inflamed parenchymal tissue. In vitro, anti–alpha-4 integrin antibodies also block alpha4–mediated cell binding to ligands, such as osteopontin and an alternatively spliced domain of fibronectin,
connecting segment 1. In vivo, natalizumab may further act to inhibit the interaction of alpha-4–expressing
leukocytes with their ligand(s) in the extracellular matrix and on parenchymal cells, thereby inhibiting
further recruitment and inflammatory activity of activated immune cells.
Criteria: CWQI HCS-0111
I.
Tysabri is medically necessary as indicated by 1 or more of the following:
a. Multiple Sclerosis with ALL of the following
i. Patient is at least 18 years or older
ii. Patient has diagnosis of relapsing-remitting MS (RRMS), secondary progressive MS
(SPMS) with relapses or progressive relapsing MS (PRMS)
iii. Confirmed diagnosis of MS as documented by laboratory report (I.E. MRI)
iv. Documented previous negative or unknown JCV antibody ELISA test within the past
6 months
v. Prescriber and patient must be enrolled in and meet the conditions of the MS
TOUCH program
vi. Must be used as single agent therapy
vii. Not used in combination with antineoplastic, immunosuppressant, or
immunomodulating agents
viii. Patient must not have a systemic medical condition resulting in significantly
compromised immune system function
b. Crohn’s disease with ALL of the following
i. Patient is at least 18 years or older
ii. Patient has moderate to severe active disease
iii. Documented trail 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
iv. Documented trial and failure on ONE TNF-Inhibitor therapy for at least 3 months,
unless contraindicated, such as Remicade (Infliximab), Cimzia (certolizumab) or
Humira (adalimumab)
v. Prescriber and patient must be enrolled in and meet the conditions of the CD
TOUCH program
vi. Used as single agent therapy [Not used concurrently with another TNF inhibitor or
immunosuppressants (e.g. 6-mercaptopurine, azathioprine,
cyclosporinemethotrexate, etc.)]
vii. Documented previous negative or unknown JCV antibody ELISA test within the past
6 months
viii. Prescriber and patient must be enrolled in and meet the conditions of the TOUCH
program
ix. Not used in combination with antineoplastic, immunosuppressant, or
immunomodulating agents
x. Patient must not have a systemic medical condition resulting in significantly
compromised immune system function
c. Renewal of Tysabri is medically necessary as indicated by ALL of the following
i. Patient continues to meet criteria above.
ii. Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity
include the following: hypersensitivity reactions; hepatoxicity; signs or symptoms
of progressive multifocal leukoencephalopathy [PML] ); development of severe
infections (including pneumonias, pneumocystis carinii pneumonia, pulmonary
mycobacterium avium intracellular, bronchopulmonary aspergillosis, herpes, urinary
tract, gastroenteritis, vaginal, tonsillitis) with ONE of the following:
1. MS diagnosis with ALL of the following
a.
b. Adequate documentation of disease stability and/or improvement
(i.e., EDSS scores, no relapse, and/or chart notes)
2. Crohn’s Disease diagnosis with ALL of the following
a. Clinical response and remission of disease is seen by 12 weeks
b. Patient has been tapered off of oral corticosteroids within six months
of starting Tysabri
c. Patient does not require additional steroid use that exceeds three
months in a calendar year to control their Crohn’s disease
d. Contraindications/Warnings:
i. Tysabri increases the risk of progressive multifocal leukoencephalopathy (PML), an
opportunistic viral infection of the brain that usually leads to death or severe
disability
ii. Patients should be monitored for signs and symptoms of PML and Tysabri
discontinued immediately at the first sign or symptom suggesting PML.
iii. Tysabri is only available through a special restricted distribution program called the
TOUCH Prescribing Program and must be administered only to patient enrolled in
this program
iv. Tysabri is contraindicated in patients who have or have had PML
v. It is contraindicated in patient who had a hypersensitivity reaction to Tysabri.
Dosage/Administration
Indication
All Indications
Dose
300 mg intravenous infusion over one hour every four
weeks
Information to be Submitted with Pre-Authorization Request:
1. Chart notes
2. Imaging studies and laboratory reports
Applicable CPT Codes:
JCode:
 J2323 – Tysabri (Elan Pharmaceuticals) 300mg injection: 1 billable unit = 1mg
NDC:

Tysabri 300mg/15ml-64406-0008-xx (Biogen Idec Inc)
Dosing Limits:
Quantity Limit (max daily dose) {Pharmacy Benefit]:
N/A
Max Units (per dose and over time) [Medical Benefit]:
Male:
300 billable units every 28 days (4 weeks)
Female:
300 billable units every 28 days (4 weeks)
Covered Diagnosis:
ICD-10
Codes
G35
K50.00
K50.011
K50.012
K50.013
Diagnosis
Multiple Sclerosis
Crohn’s disease of small intestine without complication
Crohn’s disease of small intestine with rectal bleeding
Crohn’s disease of small intestine with intestinal obstruction
Crohn’s disease of small intestine with fistula
K50.014
K50.018
K50.019
K50.10
K50.111
K50.112
K50.113
K50.114
K50.118
K50.119
K50.80
K50.811
K50.812
K50.813
K50.814
K50.818
K50.819
K50.90
K50.911
K50.912
K50.913
K50.914
K50.918
K50.919
Review Date
10/2013
12/2014
05/2015
10/2015
02/2016
Crohn’s disease of small intestine with abscess
Crohn’s disease of small intestine with other complications
Crohn’s disease of small intestine with unspecified complications
Crohn’s disease of small intestine with without complications
Crohn’s disease of large intestine without complications
Crohn’s disease of large intestine with intestinal obstruction
Crohn’s disease of large intestine with fistula
Crohn’s disease of large intestine with abscess
Crohn’s disease of large intestine with other complication
Crohn’s disease of large intestine with unspecified complications
Crohn’s disease of both small and large intestine without complications
Crohn’s disease of both small and large intestine with rectal bleeding
Crohn’s disease of both small and large intestine with intestinal obstruction
Crohn’s disease of both small and large intestine with fistula
Crohn’s disease of both small and large intestine with abscess
Crohn’s disease of both small and large intestine with other complications
Crohn’s disease of both small and large intestine with unspecified complications
Crohn’s disease, unspecified, without complications
Crohn’s disease, unspecified, with rectal bleeding
Crohn’s disease, unspecified, with intestinal obstruction
Crohn’s disease, unspecified, with fistula
Crohn’s disease, unspecified, with abscess
Crohn’s disease, unspecified, with other complication
Crohn’s disease, unspecified, with unspecified complications
Revisions
New criteria adopted from ICORE guidelines
Annual Review: Added criteria iv for MS, added
contraindications, updated references
Updated with Magellan (ICORE) criteria
Updated with ICD-10 codes, removed ICD-9 codes,
updated references
Updated with Magellan criteria, updated
references, indications
Effective Date
10/01/2013
12/31/2014
05/30/2015
10/28/2015
02/24/2016
References:
 Tysabri [package Insert]. Cambridge, MA; Biogen Idec, Inc.; May 2015. Accessed
October 2015
 Goodin DS, Cohen BA, O'Connor P, et al. Assessment: the use of natalizumab (Tysabri)
for the treatment of multiple sclerosis (an evidence-based review): report of the
Therapeutics and Technology Assessment Subcommittee of the American Academy of
Neurology. Neurology 2008; 71:766.
 Gawronski KM, Rainka MM, Patel MJ, Gengo FM. Treatment Options for Multiple
Sclerosis: Current and Emerging Therapies. Pharmacotherapy. 2010;30(9):916-927.




Goodin DS, Frohman EM, Garmany GP Jr, Halper J, Likosky WH, Lublin FD, Silberberg
DH, Stuart WH, van den Noort S. Disease modifying therapies in multiple sclerosis:
report of the Therapeutics and Technology Assessment Subcommittee of the
American Academy of Neurology and the MS Council for Clinical Practice Guidelines.
Neurology 2002 Jan 22;58(2):169-78.
Lichtenstein GR, Hanauer SB, Sandborn WJ, Practice Parameters Committee of
American College of Gastroenterology. Management of Crohn's disease in adults. Am
J Gastroenterol. 2009;104(2):465.
Best WR, Becktel JM, Singleton JW, Kern F: Development of a Crohn’s Disease Activity
Index, National Cooperative Crohn’s Disease Study. Gastroenterology 1976; 70(3):
439-444.
Terdiman JP, Gruss CB, Heidelbaugh JJ, et.al. American Gastroenterological
Association Institute guideline on the use of thiopurines, methotrexate, and anti-TNFa biologic drugs for the induction and maintenance of remission in inflammatory
Crohn’s disease. Gastroenterology. 2013 Dec; 145(6): 1459-63. Doi:
10.1053/i.gastro.2013.10.046