Use of natalizumab in multiple sclerosis patients.

Natalizumab is a monoclonal antibody indicated in Canada as monotherapy for the treatment of multiple sclerosis (MS) patients with relapsing-remitting disease. The phase III clinical trial of natalizumab monotherapy demonstrated substantial improvements in clinical and magnetic resonance imaging (MRI) parameters in patients with relapsing-remitting MS, with statistically significant reductions in annualized relapse rate (68%), sustained disability progression (42-54% over two years), and the number of gadolinium-enhancing lesions (92%) and new or enlarging T2 lesions (83%; all p<0.001 compared to placebo).1 Despite the recognized limitations of measuring surrogate endpoints such as short-term disability progression and changes in lesion burden on MRI in MS trials of short duration (i.e., two years relative to the life-long disease)2,3 clinical experience to date generally supports the efficacy and tolerability profile of this agent as reported in clinical trials. Natalizumab is generally recommended in MS patients who have had an inadequate response to, or are unable to tolerate, other therapies for MS. Although natalizumab has been available in Canada for more than two years, there remains uncertainty among community and academic neurologists on how best to utilize this drug in clinical practice. In light of rare reports of serious and potentially fatal infections (such as progressive multifocal leukoencephelopathy [PML]) and malignancies in MS patients exposed to natalizumab,1,4-6 it is paramount for clinicians to weigh the benefits of natalizumab therapy against the potential risks. The following management recommendations relating to the use of natalizumab in patients with MS were developed by a national, independent expert panel that convened in February, 2009. The primary objective was to develop a clear and practical set of consensus-basedi, non-binding recommendations on the use of natalizumab in MS patients, based on available evidence and the panel’s experience to date.ii These recommendations discuss issues related to natalizumab treatment, patient selection, and usage, many of which have not yet been formally investigated and/or for which robust evidence is currently lacking to inform clinical practice.