Bates_EU Neurology 10/03/2010 10:05 Page 58
Multiple Sclerosis
Natalizumab (Tysabri
®
) – Re-defining Efficacy in Multiple Sclerosis –
Data from Clinical Trials to Post-marketing Experience
David Bates
Professor of Clinical Neurology, Department of Neurology, The Institute of Neuroscience, Newcastle University
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 and 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 minimised 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, acts as 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, 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 neuro- these variables do not influence the subsequent progression of
degenerative disease in which T cells cross the blood–brain barrier and irreversible disability.
5
In addition to physical disability, 43% of patients
attack the myelin sheath, initiating an inflammatory cascade. The results have some degree of cognitive dysfunction.
8
The social costs of MS
are plaques of demyelination, gliosis and axonal degeneration.
1
It is are high and include limited ability to participate in employment and
the leading cause of non-traumatic disability among young adults, perform routine household tasks, limited social functioning and
with a total estimated prevalence for the last three decades of increased psychopathology.
9
MS is also a life-shortening disease,
83 cases/100,000 population and an annual European incidence causing an average 10–12-year reduction in life expectancy.
10,11
A
of 4.3 cases/100,000 population. The prevalence ratio of females to study of deaths among MS patients found that complications from MS
males is approximately 2:1
2
and may be increasing. The disease affects accounted for 47% of deaths, and the suicide rate was 7.5-fold higher
men and women in different ways, including age at onset, disease than that for the age-matched general population.
12
course and prognosis.
3
Many geographical variations affect prevalence,
including increased latitude both north and south of the equator.
4
The The clinical course of MS is heterogeneous, with variability both
onset of disease can span five decades, although it is most common between and within patients, and has been categorised as secondary
between 20 and 30 years of age. The age at onset appears to affect progressive MS (SPMS), primary progressive MS (PPMS) or relapsing–
prognosis, with younger patients generally taking longer to progress to remitting MS (RRMS); the latter accounts for 85% of MS patients in the
a worse state of disability than older patients (progression to an initial disease course. This article will focus on RRMS, which is
Expanded Disability Scale Score [EDSS] of 4, at which walking is limited).
5
characterised by relapses during which new symptoms may occur
and old ones worsen, and remissions during which the patient fully or
MS results in significant disability: many patients are unable to walk partially recovers from the deficits acquired during the relapse.
13
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 Efficacy of Current First-line
predict the time between onset of disease and onset of irreversible Disease-modifying Treatments
disability: gender, age, symptoms, disease course, degree of recovery The formation of the inflammatory lesions that characterise MS is
from the first relapse, time to second neurological episode and thought to be initiated by lymphocyte migration across the blood–
number of relapses in the first five years of the disease. However, brain barrier. This is mediated by adhesion molecules and ligands
58
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