TYSABRI SAFETY: A WELL-UNDERSTOOD PROFILE

TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML)1

PML is an opportunistic viral infection of the brain caused by the John Cunningham virus (JCV) that usually leads to death or severe disability. There is no known treatment, prevention, or cure for PML. Infection by the JC virus is required for the development of PML.

Risk factors for PML1

Evaluate 3 known PML risk factors on an individual patient basis when deciding to start or continue TYSABRI.

LENGTH OF TREATMENT DURATION

(especially beyond 2 years)

Balancing benefits and risks―based on postmarketing data out to 6 years from ~69,000 US TYSABRI patients―can inform decisions about treatment over time1

Estimated US Incidence of PML Stratified by Risk Factorb,c
ANTI-JCV ANTIBODY-
NEGATIVE PATIENTS
<1/1000
ANTI-JCV ANTIBODY-POSITIVE PATIENTS
TYSABRI Exposure No Prior Immunosuppressant Use Prior Immunosuppressant Use
1-24 months <1/1000 1/1000
25-48 months 3/1000 12/1000
49-72 months 6/1000 13/1000
ANTI-JCV ANTIBODY-
POSITIVE PATIENTS
No Prior
Immunosuppressant
Use
Prior
Immunosuppressant
Use

TYSABRI EXPOSURE

1-24
months
<1/1000 1/1000
25-48
months
3/1000 12/1000
49-72
months
12/1000 13/1000

Postmarketing data out to 6 years indicate:

  • Risk for JCV- patients remains low (<1/1000) out to 6 years, regardless of other risk factors
  • Risk for JCV+ patients increased based on the risk factors

Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom suggestive of progressive multifocal leukoencephalopathy (PML)1

Continually evaluate treatment response and disease activity as measured by MRI activity, relapse rate, and EDSS progression2

Typical symptoms associated with PML are diverse, progress over days to weeks, and may include1:

  • Progressive weakness on one side of the body or clumsiness of limbs
  • Disturbances of speech or vision
  • Changes in thinking, memory, and orientation leading to confusion and personality changes

MRI findings may be apparent before clinical signs or symptoms suggestive of PML. Periodic monitoring for radiographic signs consistent with PML should be considered to allow for an early diagnosis of PML. Consider monitoring patients at high risk for PML more frequently. 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.1

Upon initial suspicion of PML, follow these 5 steps1 :

Call Biogen (1-866-633-4636) as soon as possible to report the adverse event.

To make the diagnosis of PML, various MRI evaluations, including gadolinium-enhanced and T2-weighted scans, as well as PCR analysis of CSF for JC viral DNA, are recommended1

There are no known interventions that can reliably prevent or that can adequately treat PML if it occurs.

  • If PML is detected, action should be taken to allow immune reconstitution, which would include stopping TYSABRI, and consideration of PLEX
  • PML has been reported following discontinuation of TYSABRI in patients who did not have findings suggestive of PML at the time of discontinuation
  • Patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for approximately 6 months following discontinuation of TYSABRI

This information is provided as an educational resource for healthcare providers. It is not intended to be a substitute for consultation with your patients and review of reference material and medical literature. Healthcare providers should make all treatment decisions based on the context of the situation and their own clinical judgment.

Learn more about monitoring with TOUCH®

Because of the risk of PML, TYSABRI is available only under a restricted distribution program, the TOUCH Prescribing Program.
Only prescribers, pharmacies, and infusion sites enrolled in the TOUCH Prescribing Program (REMS program) are able to prescribe, distribute, or infuse TYSABRI.

Learn More About TOUCH®

aJCV-negative patients should be retested periodically—due to the potential for a new infection or a false-negative result. The reported rate of seroconversion (changing from JCV-negative to JCV-positive and remaining positive in subsequent testing) is 3% to 8% annually. Serostatus may change intermittently.

bThe risk estimates are based on postmarketing data in the United States from approximately 69,000 TYSABRI-exposed patients. The anti-JCV antibody status was determined using an anti-JCV antibody test (ELISA) that has been analytically and clinically validated and is configured with detection and inhibition steps to confirm the presence of JCV-specific antibodies with an analytical false-negative rate of 3%.

cData beyond 6 years of treatment are limited.