Tysabri Monotherapy and Progressive Multifocal Leukoencephalopathy -
February 5, 2010
Thirty-one cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients receiving natalizumab (Tysabri) monotherapy for multiple sclerosis (MS) worldwide. As of late January, 2010, eight patients had died. The data suggests that PML incidence increases with the number of natalizumab infusions. Worldwide, the rate of PML with natailizumab increases from 0.5 cases/1,000 patients after 1 or more doses, to 0.8 cases/1,000 patients after 12 or more doses, and to 1.3 cases/1,000 patients after 24 or more doses. To date, none of the reported postmarketing cases of PML have included patients using natalizumab for Crohn disease. PML is a viral infection of the central nervous system, mainly seen in immunosuppressed patients. Symptoms of PML include decreased mental function, speech difficulty, partial blindness, and difficulty walking.
In addition, patients who develop PML and discontinue natalizumab are at risk for a rare, severe inflammatory reaction known as Immune Reconstitution Inflammatory Syndrome (IRIS). Patients can develop IRIS while the patient is immunosuppressed or after immune recovery. In patients who were treated with plasma exchange or immunoadsorption, IRIS developed days to weeks after discontinuing natalizumab because of PML.
Natalizumab injection (Tysabri) is a monoclonal antibody approved for the treatment of relapsing MS and Crohn disease. Natalizumab is only available to patients through the TOUCH Prescribing Program. Risk for PML is considered to be higher in patients receiving concurrent immunomodulators with natalizumab compared to natalizumab monotherapy.
