Natalizumab (Tysabri▼): risk of progressive multifocal leukoencephalopathy is increased in patients who have had previous immunosuppressant treatment
- Medicines and Healthcare products Regulatory Agency
- 4 March 2011
- Therapeutic area:
Risk of developing progressive multifocal leukoencephalopathy (PML) associated with natalizumab is increased in patients who have had previous immunosuppressant therapy.
Article date: March 2011
Post-publication note: this article has been superseded. See updated information published in April 2016 for the latest advice.
Natalizumab (Tysabri▼) is a single disease-modifying therapy for patients with multiple sclerosis who have high disease activity despite treatment with beta-interferon, or who have rapidly evolving severe relapsing remitting disease. It is the first agent in its class for multiple sclerosis.
The standard dose is 300 mg natalizumab by intravenous infusion (over about 1 hour) once every 4 weeks. Patients should be observed during infusion and for 1 hour after for signs and symptoms of hypersensitivity.
Risk of progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is a rare, progressive, and demyelinating disease of the CNS that may be fatal. It is caused by activation of JC virus, which usually remains latent and typically only causes PML in immunocompromised patients. The factors leading to activation of the latent infection are not fully understood. JC virus is widespread in the general population, including patients with multiple sclerosis, and the prevalence of antibodies increases with age.
PML was identified as a safety risk associated with natalizumab at the time of licensing, and information on how to minimise this risk has been included in the summary of product characteristics.
The risk of PML increases with treatment duration, especially beyond 2 years (see Drug Safety Update March 2010).
A recent analysis of patients diagnosed with PML suggests that the risk of PML is increased in patients who have been treated with an immunosuppressant (eg, azathioprine, cyclophosphamide, mitoxantrone, and methotrexate) before receiving natalizumab. This analysis used data from an ongoing observational study (TYGRIS—Tysabri Global Observational Program In Safety) to compare the risk of PML in patients who were either treated or not treated with immunosuppressants before starting natalizumab.
New advice for healthcare professionals:
- patients should be advised that the risk of PML is greater if they have previously taken an immunosuppressant
Previous advice remains and is that:
- patients should be advised that the risk of PML increases with duration of treatment with natalizumab, especially beyond 2 years
- patients should be informed about the risks via a treatment initiation /continuation form and updated patient information leaflet
- natalizumab should be promptly discontinued if PML is suspected, with subsequent appropriate evaluation including standardised MRI and lumbar puncture
- further information for prescribers is available in the Physician Information and Management Guidelines (for further information, see a letter sent to healthcare professionals in January 2011).
Reporting of suspected adverse reactions
Natalizumab is under intensive monitoring by the MHRA, and healthcare professionals are reminded to report suspected adverse reactions promptly via the Yellow Card Scheme.
BNF section 8.2.4 Other immunomodulating drugs
Article citation: Drug Safety Update March 2011, vol 4 issue 8: A2.
Published: 4 March 2011
Therapeutic area: Neurology