Natalizumab (Tysabri®)—Re-defining Efficacy in Multiple Sclerosis— Data from Clinical Trials to Post-marketing Experience
Natalizumab (Tysabri®)—Re-defining Efficacy in Multiple Sclerosis— Data from Clinical Trials to Post-marketing Experience
US Neurology, 2010;5(2):72-7
Abstract
Multiple sclerosis (MS) is a chronic, disabling condition with severe clinical and social consequences. Current first-line disease-modifying treatments have limited efficacy and do not halt long-term disease progression in the majority of patients. Natalizumab (Tysabri®) is the only monoclonal antibody licensed for use in relapsing–remitting MS (RRMS). It is regarded by many neurologists as the most effective MS drug on the market today, and has the potential to re-define successful MS therapy. Its efficacy has been demonstrated both in large-scale clinical trials and in post-marketing settings. Beneficial effects include reduction of relapse rates and disease progression, as well as magnetic resonance imaging (MRI) measures of disease activity. Natalizumab treatment has a substantial impact on patient quality of life. Moreover, patients have shown significant improvement following natalizumab treatment, making continuing clinical remission a realistic goal in MS for the first time. However, the benefits of natalizumab must be balanced against risk. Progressive multifocal leukoencephalopathy (PML) is a rare event associated with natalizumab treatment that may be minimized with a risk management plan to educate physicians on patient selection and management.
Keywords
AFFIRM, natalizumab, progressive multifocal leukoencephalopathy (PML), relapsing–remitting multiple sclerosis (RRMS), Tysabri
Disclosure: David Bates, MA, FRCP, acts as an international adviser to Biogen Idec and other pharmaceutical companies on the role of therapy in multiple sclerosis.
Received: November 17, 2009 Accepted: January 8, 2010
Correspondence: David Bates, MA, FRCP, Department of Neurology, The Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK. E: david.bates@ncl.ac.uk
Support: Editorial assistance was provided by James Gilbart at Touch Briefings and was funded by Biogen Idec.
Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative disease in which T cells cross the blood–brain barrier and attack the myelin sheath, initiating an inflammatory cascade. The consequences of these events are plaques of demyelination, gliosis, and axonal degeneration.1 MS is the leading cause of non-traumatic disability among young adults, with a total estimated prevalence for the last three decades of 83 cases/100,000 population and an annual European incidence of 4.3 cases/100,000 population. The prevalence ratio of females to males is approximately 2:12 and may be increasing. The disease affects men and women in different ways, including age at onset, disease course, and prognosis.3 Many geographical variations affect prevalence, including increased latitude both north and south of the equator.4 The onset of MS can span five decades, although it is most common between 20 and 30 years of age. The age at onset appears to affect prognosis, with younger patients generally taking longer to progress to a worse state of disability than older patients (progression to an Expanded Disability Scale Score [EDSS] of 4, at which walking is limited).5
MS results in significant disability: many patients are unable to walk unaided after a median of 15 years,6 and are wheelchair-bound by 25 years after disease onset.7 A number of variables have been shown to predict the time between onset of disease and onset of irreversible disability: gender, age, symptoms, disease course, degree of recovery from the first relapse, time to second neurological episode, and number of relapses in the first five years of the disease. However, these variables do not influence the subsequent progression of irreversible disability.5 In addition to physical disability, 43% of MS patients have some degree of cognitive dysfunction.8 The social cost of MS is high and includes a limited ability to participate in the workforce, perform routine household tasks, and function socially, as well as increased psychopathology.9 Multiple sclerosis is also a life-shortening disease, causing an average 10–12-year reduction in life expectancy.10,11 A study of deaths among MS patients found that complications from MS accounted for 47% of deaths, and the suicide rate was 7.5-fold higher than that for the age-matched general population.12
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Keywords:
AFFIRM, natalizumab, progressive multifocal leukoencephalopathy (PML), relapsing–remitting multiple sclerosis (RRMS), Tysabri, multiple sclerosis causes, multiple sclerosis prognosis, multiple sclerosis symptoms, morto neurone disease, natalizumab tysabri, natalizumab multiple sclerosis,
