According to a notification from the US FDA, the risk of developing progressive multifocal leukoencephalopathy (PML) with natalizumab (Tysabri®) increases with the number of infusions received.

There have been no reports of PML in patients treated for less than 12 months since the remarketing of natalizumab.  In patients treated with 24 to 36 infusions, the overall worldwide rate and the rate in the US of developing PML is similar to the rate seen during clinical trials (1 case per 1,000 patients treated).  Outside of the US, the rate is approximately 2 cases per 1,000 patients.  The reasons for this difference are unknown. There is limited clinical experience beyond 36 natalizumab infusions either in clinical trials or in the post-marketing setting.  This new safety information, based on 31 confirmed cases of PML received by the FDA as of January 2010, will be added to the drug label and patient Medication Guide for natalizumab in the US.

Information on the occurrence of Immune Reconstitution Inflammatory Syndrome (IRIS) in patients who have developed PML and subsequently discontinued natalizumab will also be included in the drug label and patient Medication Guide.  IRIS is a rare condition characterised by a severe inflammatory response that can occur during or following immune system recovery, causing an unexpected decline in a patient’s condition after return of immune function.  It has been reported in patients who discontinue natalizumab as a result of developing PML, but not in patients who discontinue natalizumab for other reasons.