Natalizumab in multiple sclerosis: proceed with caution?

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the CNS. In a Phase II clinical trial, natalizumab was shown to reduce the relapses in patients with relapsing MS, without improving the disability score. After 1-year of Phase III clinical trials, natalizumab was approved by the FDA for use in relapsing MS but was withdrawn 3 months later, due to two reported cases of progressive multifocal leukoencephalopathy (PML). The completed clinical trials with natalizumab for relapsing MS have recently been reported. In a trial of 1171 subjects with relapsing MS, natalizumab alone was shown to reduce the relapse rate and lesions, without causing PML. Although natalizumab was also shown to reduce the relapse rates and lesions in patients taking IFN-beta, two cases of PML with natalizumab occurred in these patients. An assessment of patients who had taken natalizumab for 1 - 2 years (similar to 3000), showed the incidence of PML to be 1/1000. A drug that is useful in relapsing MS will be used as along-term therapy in large numbers of patients. For instance, in the 3 months that natalizumab was registered, 5000 patients commenced taking it. In the author's opinion, large numbers of patients should not be allowed to take natalizumab until its safety has been monitored in the long-term use in a clinical trial environment.