Natalizumab and PML: a risky business?

The development of new treatments and their incorporation into the care of patients requires integration of a substantial body of information to achieve optimal outcomes for the greatest number of patients. Evidence based medical practice is evolving, and deserves support and encouragement, particularly as complicated risk–benefit decisions must be addressed in practice. In this issue, Verbeeck et al 1 ( see page 1393 ) provide useful observations for clinicians framing some of the risks associated with natalizumab (Tysabri), a drug approved by the US Food and Drug Administration (FDA) on 14 January 2008 for the treatment of Crohn’s disease. Natalizumab is a humanized monoclonal antibody against α4-integrin first approved for treatment of relapsing, remitting multiple sclerosis (MS). This drug reduces the activity of MS as reflected by development of new magnetic resonance (MR) brain lesions, and by slowing progression of disability.2 Subsequently, studies support efficacy for Crohn’s disease.3 4 This efficacy is believed to result from blockade of integrin mediated migration of inflammatory cells involved with diseases such as MS or Crohn’s disease. While critical disease-modifying activity is available through the use of natalizumab, its use has been impacted by toxicity. During the blinded clinical trials, the safety profile was excellent, but shortly after FDA approval of natalizumab for MS, three cases of progressive multifocal leukoencephalopathy (PML) were reported resulting in suspension of all dosing with this drug. Two cases were MS patients also on interferon β5 6 and one had Crohn’s disease concurrently treated with …