Download - Thomson One

Multiple Sclerosis
Glossary of Terms
Annualized relapse
rate (ARR)
The average number of relapses a person with multiple sclerosis (MS)
has per year1. It is a key measure of relapsing MS (RMS) disease
activity.
Autoimmune disease
A healthy immune system knows which tissues are part of the
person's body and which are 'foreign' - e.g. a virus or bacterial
infection - and need attacking. In some conditions, for reasons that
aren't known, this protective mechanism fails to work. The body’s own
immune system attacks itself (or part of itself) as if it were a foreign
invader. These conditions are called autoimmune diseases2. In MS,
the immune system attacks the cells of the central nervous system
(CNS)3.
Axon
Also known as a nerve fiber, it projects from the body of a neuron and
conducts the electrical impulses along the nerve4. The axon is usually
insulated by a myelin sheath4, but in MS, the myelin sheath is
damaged or destroyed and this affects the conduction of impulses
along the axon.
Brain volume loss
(BVL)
Also referred to as brain shrinkage, BVL refers to the loss of brain
tissue (including myelin and axons) and changes in the water
containing spaces in and around the brain. It is measured by Magnetic
Resonance Imaging (MRI). MS patients lose brain volume around
three to five times faster than people without MS, and this loss has
been associated with physical (e.g. walking) and cognitive (e.g. mental
tasks or memory) problems5,6.
Central nervous
system (CNS)
Part of the nervous system consisting of the brain, the nerves leading
to the eyes and the spinal cord7. It is involved in coordinating voluntary
and involuntary actions and transmitting signals between different
parts of the body7. It is this part of the nervous system that is damaged
in MS3.
Chronic
A chronic disease is a long-lasting condition that can be controlled but
not cured. Chronic diseases generally progress slowly.
Cognition
The term 'cognition' refers to the full range of mental skills and
abilities, including memory, concentration, the process of thinking,
decision-making and understanding. People with MS can experience
difficulties with cognition. For some, cognitive problems come and go
in the same way other symptoms do, but for others cognitive problems
will develop soon after the onset of MS and remain8.
Demyelination
When the insulating coat of nerves and nerve extensions, that enables
nerves to work properly, is damaged or stripped away9.
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2015 Novartis Pharmaceuticals
GLNS/GILE/0016
March 2015
Diffuse damage
Diffuse damage is widespread inflammatory damage throughout the
brain, in comparison to focal damage which refers to distinct areas of
damage. Damage to the brain occurs early in the course of MS, as
early as the first neurological episode or single attack of symptoms.
Diffuse damage reflects the cumulative loss of tissue, including
neurons, and is not visible on conventional MRI scans, so it often goes
unnoticed. Diffuse damage can be captured by measuring brain
volume loss and is associated with the loss of both physical (e.g.
walking) and cognitive (e.g. memory) function over time10,11,12.
Disability progression
Confirmed disability progression is the rate at which a person’s
disability has worsened over time. In MS clinical trials, it is usually
measured using the Expanded Disability Status Scale (EDSS) over
two time points. A 6 month measure is considered a more reliable
assessment of long term disability accumulation13,14. Confirmed
disability progression is a key measure of MS disease activity.
Disease-modifying
therapy (DMT)
A treatment that impacts the natural course of the disease15.
Expanded Disability
Status Scale (EDSS)
A scale used by physicians to quantify a person with MS’ level of
disability. It is widely used as an endpoint in clinical trials and to
assess overall disability in people with MS and monitor changes in
their disability over time. Measurements are generally taken at 3 or 6
months, with 6 months considered to be a more reliable assessment
of long term disability accumulation 13,14
Focal damage
Distinct areas of inflammatory damage in the brain (lesions) that can
clinically present as relapses. Focal damage results in the loss of brain
tissue. If a patient doesn’t recover from a relapse completely, disability
may accumulate for the patient9,10,11.
Gd+ T1 lesion
Lesions (areas of damage) that can be seen on a T1-weighted
magnetic resonance imaging (MRI) scan, where a contrast agent,
gadolium is injected before the scan. When injected before a scan,
gadolinium makes it possible to distinguish between active MS lesions
and older areas of scarring16. These types of scans are often used
when diagnosing MS or measuring a patient’s response to treatment.
Inflammation
Inflammation is part of the body’s immune response to harm and
damage17. In MS, inflammation can lead to significant nerve damage
and the lesions (areas of damage) that result are visible on MRI
scans18.
Lesion
A damaged area of tissue, usually caused by disease or trauma. In
MS, the number and volume of lesions in the central nervous system,
as measured by magnetic resonance imaging (MRI), has been shown
to be associated with relapses and disability19.
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2015 Novartis Pharmaceuticals
GLNS/GILE/0016
March 2015
Lesion load
An estimate of the cumulative volume of damaged tissue (lesions) as
identified by magnetic resonance imaging (MRI). Lesion load has been
shown to be associated with relapses and disability20.
Lymphocytes
Small white blood cells of the immune system occurring predominantly
in the lymphatic system21. In some conditions, for reasons that aren't
known, the immune system mistakenly turns on the body's own tissue.
In MS lymphocytes attack the myelin sheath which covers the nerves
within the CNS2.
Magnetic resonance
imaging (MRI)
A type of scan that uses strong magnetic fields and radio waves to
produce digital images of inside the body22. In MS, it is used to provide
an estimate of the number and volume of lesions in the CNS and
measure brain volume changes.
Multiple sclerosis (MS)
Multiple sclerosis (MS) is the term used for a disease where the
immune system mistakenly attacks healthy cells in the central nervous
system (CNS) – the brain, the nerves leading to the eyes and the
spine3. The evolution of MS can result in a progressive loss of
function, including for example both physical (e.g. walking) and
cognitive (e.g. concentrating) functions.
Myelin sheath
The protective coating (insulation) around a nerve cell and the fiberlike extension of the nerve. The myelin sheath is essential for the
proper functioning of the nervous system. In MS, the cells of the
immune system damage the myelin sheath and signal conduction
along the nerves is slower and less complete or interrupted3.
No evidence of disease NEDA-4 is achieved when a patient has no relapses, no new MRI
activity (NEDA-4)
lesions, no brain shrinkage (brain volume loss) and no disability
progression. These are the four key measures of relapsing MS
disease activity23.
Neurodegenerative
disease
A disease characterized by damage to nerve cells that gets worse
over time24. MS, Parkinson’s Disease and Alzheimer’s Disease are all
examples of neurodegenerative diseases.
Neuron/nerve cell
A cell present in the nervous system that processes and transmits
information25.
Physical function
Mobility (or movement), muscle control, balance and activities such as
walking and climbing stairs26.
Primary-progressive
multiple sclerosis
(PPMS)
A type of MS characterized by a person’s symptoms gradually getting
worse over time, rather than appearing in sudden attacks.
Approximately 10% of people diagnosed with MS have PPMS27.
Real world evidence
Data collected about a treatment in a practical, real-life setting rather
than data taken from a clinical trial28. Provides valuable information on
outcomes in clinical practice, including the benefit-risk ratio of a
treatment, and is needed to complement data from clinical trials.
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2015 Novartis Pharmaceuticals
GLNS/GILE/0016
March 2015
Relapse
The appearance of new symptoms of MS, or the return of old
symptoms, for a period of 24 hours or more in the absence of a
change in core body temperature or infection29. Relapses may have
an acute disabling impact on the individual’s life. Incomplete recovery
from a relapse can significantly advance the level of disability30.
Relapsing multiple
sclerosis (RMS)
Relapsing MS is characterized by attacks (relapses) where there is a
sudden appearance of previous and /or new symptoms. There are two
types of RMS: Relapsing remitting MS (RRMS) and secondaryprogressive multiple sclerosis (SPMS)29,31,32.
Relapsing-remitting
multiple sclerosis
(RRMS)
A type of MS characterized by relapses with worsening neurological
function, followed by periods of remission where a person partially or
fully recovers. Approximately 85% of people with MS are initially
diagnosed with this form of the disease29.
Remission
A period of time during which a person with MS’ symptoms may
lessen or completely stop29.
Secondaryprogressive multiple
sclerosis (SPMS)
A type of MS characterized by the gradual worsening of a person’s
neurological function (accumulation of permanent disability) between
relapses31. The majority of people with RRMS will develop SPMS over
time (25% by 10 years, 50% by 20 years, and >75% by 30 years)33.
The transition from RRMS to SPMS is usually gradual34.
Sphingosine 1phosphate receptor
A type of receptor expressed on a wide range of cells that are involved
in the biological processes relevant to MS35.
Symptomatic
treatment
A treatment that targets the symptoms of a disease, such as spasticity
(muscle spasms or stiffness), depression, bladder disorder or
problems walking in MS, but does not alter the course of the disease.
T2 lesion
Lesions identified by a T2-weighted magnetic resonance imaging
(MRI) scan (a specific scan technique to visualize brain tissue). These
types of scans show both new or active disease and old lesions, and
are often used when diagnosing MS and measuring a patient’s
response to treatment22.
References:
1
Roskell NS et al. Annualized relapse rate of first-line treatments for multiple sclerosis: a meta-analysis, including indirect
comparisons versus fingolimod. Curr Med Res Opin. 2012 May;28(5):767-80.
http://www.mstrust.org.uk/atoz/autoimmunity.jsp. Last accessed March 2015.
3
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001747/. Last accessed March 2015.
4
http://www.britannica.com/EBchecked/topic/46342/axon. Last accessed March 2015.
5
Calabrese M et al. Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis.
Arch Neurol. 2009 Sep;66(9):1144-50.
6
Bakshi R. Regional brain atrophy is associated with physical disability in multiple sclerosis: semiquantitative magnetic
resonance imaging and relationship to clinical findings. J Neuroimaging. 2001;11(2):129–36.
7
http://mcb.berkeley.edu/courses/mcb135e/central.html. Last accessed March 2015.
8
http://www.mstrust.org.uk/downloads/cognition.pdf. Last accessed March 2015.
9
http://www.msif.org/about-ms/what-is-ms/. Last accessed March 2015.
10
Filippi M et al. Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol. 2012 Apr;11(4):34960.
11
Kutzelnigg A. et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005 Nov;128(Pt
11):2705-12.
12
Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy correlates with treatment effect on disability in
multiple sclerosis. Ann Neurol. 2014 Jan;75(1):43-9.
2
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2015 Novartis Pharmaceuticals
GLNS/GILE/0016
March 2015
13
Healy BC et al. Assessment of definitions of sustained disease progression in relapsing-remitting multiple sclerosis. Mult
Scler Int. 2013; 2013:189624.
Cohen, JA, et al. Disability outcome measures in multiple sclerosis clinical trials: current status and future prospects. Lancet
Neurol 2012 May;11(5):467-76.
15
http://www.nationalmssociety.org/Treating-MS/Medications. Accessed March 2015.
16
http://www.mstrust.org.uk/atoz/gadolinium.jsp. Last access March 2015.
17
http://www.medicalnewstoday.com/articles/248423.php. Last accessed March 2015.
18
http://www.mswatch.ca/en/learn-about-MS/advances-in-MS/inflammation-and-neurodegeneration-in-MS.aspx. Last accessed
March 2015.
19
Sormani MP, Bruzzi P. MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials.
Lancet Neurol. 2013Jul;12(7):669-76.
20
Popescu V, et al. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg
Psychiatry. 2013 Oct;84(10):1082-91. doi: 10.1136/jnnp-2012-304094. Epub 2013 Mar 23.
21
http://www.cancer.gov/Common/PopUps/popDefinition.aspx?id=45765&version=Patient&language=English. Last accessed
March 2015.
22
http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/diagnosing-ms/magnetic-resonanceimaging-mri/index.aspx. Last accessed March 2015.
23
http://www.mstrust.org.uk/news/article.jsp?id=5893. Last accessed March 2015.
24
http://www.neurodegenerationresearch.eu/about/what/. Last accessed March 2015.
25
Lodish H et al. Molecular Cell Biology. 4th edition. 2000. Chapter 21, Nerve Cells.
26
http://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms. Accessed March 2015.
27
http://www.mssociety.org.uk/what-is-ms/types-of-ms/primary-progressive-ppms. Last accessed March 2015.
28
https://www.ispor.org/News/articles/Oct07/RLD.asp. Last accessed March 2015.
29
http://www.mssociety.org.uk/what-is-ms/types-of-ms/relapsing-remitting-rrms. Last accessed March 2015.
30
Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology.
2003;61(11):1528-1532.
31
http://www.nationalmssociety.org/What-is-MS/Types-of-MS/Secondary-progressive-MS. Last accessed March 2015.
32
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/03/WC500185161.pdf. Accessed March
2015.
33
Tremlett H, et al. The natural history of secondary-progressive multiple sclerosis Mult Scler. 2008:14:314-324.
34
Lublin FD, Reingold SC, Cohen JA et al. Defining the clinical course of multiple sclerosis. Neurology. 2014; 83(3): 278–286.
35
Chun J, Hartung HP. Mechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis. Clin Neuropharmacol. 2010
March-April;33(2):91-101.
14
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2015 Novartis Pharmaceuticals
GLNS/GILE/0016
March 2015