Approved Risk Evaluation and Mitigation Strategies (REMS)

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Tysabri (natalizumab)

BLA #125104

REMS last update: 04/30/2018

Goals
Summary
REMS Materials
Update history

What is the purpose of the REMS?

The goals of the Tysabri REMS are:

To inform prescribers, infusion center healthcare providers, and patients about the risk of progressive multifocal leukoencephalopathy (PML) associated with TYSABRI including the increased risk of PML with longer treatment duration, prior immunosuppressant use and the presence of anti-JCV antibodies.
To warn against concurrent use with antineoplastic, immunosuppressant, or immunomodulating agents, and in patients who are immunocompromised.
To promote early diagnosis of PML and timely discontinuation of TYSABRI in the event of suspected PML.

What do participants need to know?

Below is a general overview of the REMS for all REMS participants (e.g., patients, pharmacies, and healthcare providers). See the application holder(s) REMS Website or the approved REMS materials for more information.

View application holder(s) REMS Website

Infusion centers that dispense Tysabri must

To become certified to dispense	Receive training provided by the sponsor. Enroll in the REMS Program by completing the Infusion Site Enrollment Form. \| Infusion Site Enrollment Form \| Complete and submit the Pre-infusion Patient Checklist. Provide the patient with the Medication Guide.
At all times	Comply with audits carried out by the application holder or to ensure that all processes and procedures are in place and are being followed.

Healthcare Providers who prescribe Tysabri must

To become certified to prescribe	Review the drug’s Prescribing Information. Review the Educational Slide Set and Prescribing Program Enrollment Kit. \| Educational Slide Set \| Enroll in the REMS by completing the appropriate Prescriber/Patient Enrollment Form and submitting it to the REMS Program.
Before treatment initiation	Counsel the patient on the benefits and risks of treatment using the Medication Guide and Prescriber/Patient Enrollment Form. Counsel the patient on to promptly report any new or worsening symptoms that persist over several days, especially nervous system symptoms. For patients with Crohn's Disease, counsel the patient on other Crohn’s Disease treatment options Provide the patient with the Medication Guide. Enroll the patient by completing and submitting the appropriate Prescriber/Patient Enrollment Form to the REMS Program. Provide a completed copy of the form to the patient.
During treatment; at 3 and 6 months after the first infusion and every 6 months thereafter until treatment discontinuation	Assess the patient’s signs and symptoms for progressive multifocal leukoencephalopathy (PML).
During treatment; every 6 months	To authorize continued treatment, complete and submit the appropriate Patient Status Report and Reauthorization Questionnaire.
At treatment discontinuation	Complete and submit the Initial Discontinuation Questionnaire. \| Initial Discontinuation Questionnaire - Crohn's Disease \| For at least six months, assesses the patient’s signs and symptoms for PML.
After treatment discontinuation; at 6 months	Complete and submit the 6-Month Discontinuation Questionnaire. \| 6-Month Discontinuation Questionnaire (CD) \|
At all times	Report cases of PML, hospitalizations due to opportunistic infection, or deaths to sponsor.

Patients who are prescribed Tysabri

Before the first prescription	Review the Medication Guide and appropriate Prescriber/Patient Enrollment Form. Enroll in the REMS Program by completing the appropriate Prescriber/Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS Program Receive counseling from the prescriber on the benefits and risks of treatment. For a patient with Crohn’s Disease, receive counseling from the prescriber on other Crohn’s Disease treatment options
During treatment	Be monitored for signs and symptoms of progressive multifocal leukoencephalopathy (PML).
After treatment discontinuation	Be monitored for signs and symptoms of progressive multifocal leukoencephalopathy (PML).
At all times	Inform the prescriber if any new or worsening symptoms that persist over several days, especially nervous system symptoms

Pharmacies that dispense Tysabri must

To become certified to dispense	Receive training provided by the sponsor. Enroll in the REMS Program by completing the Certified Pharmacy Enrollment Form. \| Certified Pharmacy Enrollment Form \|
At all times	Comply with audits carried out by the sponsor or to ensure that all processes and procedures are in place and are being followed.

What materials are included in the REMS?

The REMS includes a REMS Document. In addition, the REMS includes the following materials intended for patients and healthcare providers. For a specific Medication Guide of a product in the Tysabri REMS, see the DailyMed link(s).

Material Name	Material Name Link
6-Month Discontinuation Questionnaire (CD) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_6-Month_Discontinuation_Questionnaire_(CD).pdf
6-Month Discontinuation Questionnaire (MS) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Initial_Discontinuation_Questionnaire_(MS).pdf
Certified Pharmacy Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Certified_Pharmacy_Enrollment_Form.pdf
Helpful Information for Evaluation of New Neurologic Symptoms in Patients Receiving Tysabri (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Helpful_Information_for_ Evaluation_of_New_Neurologic_Symptoms_in_Patients_Receiving_Tysabri_(MS).pdf
Infusion Site Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Infusion_Site_Enrollment_Form.pdf
Initial Discontinuation Questionaire (CD) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018-04_30_Initial_Discontinuation_Questionnaire_(CD).pdf
Initial Discontinuation Questionaire (MS) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_6-Month_Discontinuation_Questionnaire_(MS).pdf
Patient Status Report and Reauthorization Questionnaire (CD) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Patient_Status_Report_and_Reauthorization_ Questionnaire_(CD).pdf
Patient Status Report and Reauthorization Questionnaire (MS) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Patient_Status_Report_and_Reauthorization_Questionnaire_(MS).pdf
Pre-Infusion Patient Checklist (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Pre-Infusion_Patient_Checklist.pdf
Prescriber/Patient Enrollment Form (CD) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Prescriber_Pateint_Enrollment_Form_(CD).pdf
Prescriber/Patient Enrollment Form (MS) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Prescriber_Patient_Enrollment_Form_(MS).pdf
REMS document (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_REMS_Document.pdf
REMS full (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_REMS_Full.pdf
TOUCH On-Line REMS Website Screenshots (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_TOUCH_On-Line_REMS_Website_Screenshots.pdf
TOUCH Prescribing Program Educational Slide Set (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_TOUCH_Prescribing_ Program_Educational_Slide_Set.pdf
TOUCH Prescribing Program Overview (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_TOUCH_Prescribing_Program_Overview.pdf
Understanding PML for Gastroenterologists (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tysabri_2018_04_30_Understanding_PML_for_Gastroenterologists.pdf

What updates have been made to the REMS?

Date	Summary of change
04/30/2018	Editorial revisions.
04/18/2018	Modified to: Change selected REMS materials to reflect the addition of information noting that the risk of developing PML may be associated with relative levels of serum anti-JCV antibody compared to a calibrator as measured by ELISA (often described as an anti-JCV antibody index value). This information has been included in the TOUCH Prescribing Program Educational Slide Deck, and the following statement has been added to selected REMS forms (the Prescriber/Patient Enrollment Forms, the Patient Status Report and Reauthorization Questionnaires, the Initial Discontinuation Questionnaires, and the 6- Month Discontinuation Questionnaire [MS]): “If an anti-JCV antibody index value is available, please record it here:__”. Removal of 12-Week Questionnaire for Crohn’s Disease from the REMS. Changes to REMS educational materials to align with labeling changes approved on August 16, 2017, pertaining to JCV granule cell neuronopathy, MRI monitoring for PML, anti-JCV antibody testing following use of intravenous immunoglobulin, and acute retinal necrosis caused by herpes viruses. Minor formatting changes and editorial revisions.
10/14/2016	Revised to correct typographical error(s).
09/22/2016	Modified to: Change the REMS to be consistent with safety labeling changes approved on May 18, 2016. The approved safety labeling change included the addition of “Periodic monitoring for radiographic signs consistent with PML should be considered to allow for an early diagnosis of PML. Lower PML-related mortality and morbidity have been reported following Tysabri discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis” within Section 5.1—Progressive Multifocal Leukoencephalopathy of the prescribing information. Change the sponsor name change from Biogen Idec to Biogen in the REMS document and all REMS materials. Update the list of immunosuppressants, antineoplastics, and immunomodulators with a recently approved medication for multiple sclerosis (Zinbryta [daclizumab]) in the REMS materials. Change the signature statements to enable certified prescribers to delegate the completion of the forms to individuals within their office who are not certified prescribers in the reauthorization and discontinuation status forms. Make format and editorial changes, typographical corrections, and update version and copyright dating throughout the REMS materials. Delete the REMS call center hours of availability from all REMS materials.
05/12/2015	Modified to: Be consistent with revisions to approved labeling in the Medication Guide and REMS forms and materials. Reflect your current trademark guidelines and the new version number in the appended REMS materials. Include products approved for multiple sclerosis and Crohn’s disease since the last REMS modification in the Prescriber-Patient Enrollment Forms and Pre-Infusion Patient Checklists. Include new products in the lists of immunomodulatory or immunosuppressant products the patient currently receives or has received in the previous 6 months in the Patient Status Report and Reauthorization Questionnaires and the Patient Initial Discontinuation Questionnaire—CD.
12/15/2013	Modified to reflect the revision to the indication statement language and the new risk information regarding hepatotoxicity, meningitis, and encephalitis being approved with these supplements in the REMS document, multiple REMS forms and materials, and the Medication Guide.
05/24/2013	Modified to include information about monitoring of PML after discontinuation of Tysabri (natalizumab) in the Medication Guide, REMS document and the REMS materials (e.g., Prescriber/Patient Enrollment Forms and Reauthorization and Discontinuation Questionnaires for Multiple Sclerosis and Crohn’s Disease patients and the Understanding PML for Gastroenterologists document).
01/20/2012	Modified to include information about PML risk stratification in the Medication Guide, REMS document and REMS materials.
10/07/2011	Approval of the REMS.

Disclaimer: This webpage provides general information about REMS programs to various REMS participants (e.g., patients, pharmacies, and healthcare providers). The summary information provided herein is not comprehensive and may not include all of the information relevant to REMS participants. This webpage does not constitute a replacement, modification, or revision of the approved REMS document, including any appended REMS materials. Refer to the approved REMS document for complete information on the REMS requirements for each approved application.