Natalizumab (TYSABRI) and multiple sclerosis. With longer follow-up: even more toxic than suspected.

The standard disease-modifying treatment for patients with relapsing-remitting multiple sclerosis is interferon beta injection, in the absence of a better alternative. In 2007, natalizumab had an unfavourable harm-benefit balance in patients with severe multiple sclerosis in whom interferon beta was ineffective, due to insufficient evidence of efficacy and a risk of life-threatening progressive multifocal leukoencephalopathy. In 2014, we found no new comparative trials focusing on the efficacy of natalizumab monotherapy in its authorised indications in the EU. Post-marketing data confirm the adverse effects identified in clinical trials, including serious and life-threatening opportunistic infections, particularly progressive multifocal leukoencephalopathy in about two per thousand treated patients (an incidence twice as high as initially estimated), and potentially severe hypersensitivity reactions. An increased risk of cancer in the long term cannot be ruled out. Post-marketing data also show that natalizumab can cause severe liver damage. In addition, natalizumab withdrawal because of progressive multifocal leukoencephalopathy almost always triggers an immune reconsti- tution syndrome that can lead to neurological complications or even death. In practice, regardless of the severity of multiple sclerosis, it does not seem reasonable to expose patients to the many serious adverse effects of natalizumab for such an uncertain benefit.