Introduction to Best practice recommendations for the selection and management of patients with MS on natalizumab

Natalizumab (TYSABRI ; Biogen Idec, Inc. and Elan Pharmaceuticals, Inc.) is the first of a new generation of therapies for multiple sclerosis (MS) that may be an effective alternative for patients who do not respond well to interferon b (IFNb) products or glatiramer acetate, or for patients with more severe disease. Although natalizumab is highly effective, it is associated with a rare risk of the development of progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS) caused by lytic infection of oligodendrocytes by the papovavirus JC (JCV). This supplement is intended to aid physicians in making informed decisions about using natalizumab by providing further information regarding the risks associated with natalizumab, and how best to minimize these risks. Similar to other autoimmune diseases, as newer, more effective therapies are developed for the treatment of MS, these therapies will likely be associated with increased risks. Highly effective therapies, such as natalizumab, may be associated with higher risks, but these risks should be weighed against the adverse impact of the disease. Therefore, when making treatment recommendations to their patients, neurologists must evaluate the trade-offs between the benefits and risks of available treatment options in the context of the specific clinical profile of individual patients, as well as their risk tolerance. Factors that should be considered when assessing the risk/benefit profile of a therapy include the likely progression of MS associated neurological impairment, the relative efficacy of available agents, the incidence of serious adverse events, available clinical surveillance and management protocols, and outcomes from use of these protocols. During a lifetime, the majority of patients with MS incur substantial physical or cognitive disability, in addition to a reduced lifespan compared with the general population. In a chart review study by Grytten et al., health records in western Norway from 1953 to 2003 were reviewed to determine the relative survival of MS patients compared with the general population. Results showed that the median survival time after diagnosis was 41 years in patients with MS versus a median survival of 49 years for the general population of that age cohort. Consistent with these results, in a review of 33 MS-related epidemiological studies, Ragonese et al. found that patients with MS lose between 5 and 10 years of their estimated lifespan, and tend to survive 20 to 45 years after initial symptoms emerge. Disease severity in patients with MS is correlated strongly with mortality. Risk of death for patients with an Expanded Disability Status Scale (EDSS) score of 7.5 or greater was more than twice of that for patients with less severe disability (EDSS 7.0) and more than 4 times of that for ageand sex-matched healthy controls. In the recently completed, long-term, follow-up study of patients who participated in the phase III trial of intramuscular IFNb-1a (the ASSURANCE study), 14 (10%) of 136 enrolled patients were deceased at 17 years. The accrual of disability in MS over time has been documented in a number of studies and in various MS registries worldwide. Across these studies and on a population basis, cohorts of patients with MS appear to