2. is an inflammatory disease
in which the fatty myelin
sheaths around the axons
of the brain and spinal
cord are damaged,
leading to demyelination and
scarring as well as a broad
spectrum of signs and
symptoms
MULTIPLE
SCLEROSIS
2
3. Anatomy and Physiology
In the normal nerve fiber, the centralcore
of the fiber (axon) conducts the action potential for cellmovement.
This large fiberis surrounded by a myelin
sheath, made up oflipoproteins.
The sheath insulates the fiber for better nerve cell transmission.
3
4. The myelin sheath is so thick thatalmost no ionscan flow through it. They must be
transmitted through nodesof Ranvier, which occur once every 1-3 mm along the
sheath.
These nodes create “saltatory conduction” which allows the nerve impulse to
jumpalong the fiber in succession, leading to transmission of theimpulse.
This “saltatoryconduction” increases thevelocity of myelinated fiber
transmissionas much as 5-50 fold.
Small unmyelinated nerve fibers haveas
littlevelocity as 0.25 m/sec while large
mylinated fibers transmit at velocities
reaching 100 m/sec which is approximately
the length of a football field in one second.
4
5. Anatomy and Physiology
In patients withmultiplesclerosis, the myelin
sheath is attackedbyan immuneresponse.
Specifically, CD4 T cells (helps suppress or
regulate immune responses), macrophages and
microglial cells initiate an attack on the sheath
after passing through the BBB.
The attacks leave holes in the myelin, causing
the axon to be exposed, decreasing conduction
of the nerve impulses in the CNS and thePNS.
This leads toa slowing of conduction or
complete failureof the impulse toreach
itsdestination.
5
6. Blood–brain barrier disruption
The BBB is composed of endothelial cells which line the blood vessel
wallsof the central nervoussystem.
Compared to normal endothelial cells, the cells lining the BBB are
connected by occludin and claudin which form tight junctions in order to
createa barrier to keep out larger moleculessuch as proteins.
In order topass through, molecules must be taken in by transport
proteins or an alteration in the BBB permeability mustoccur*
6
8. Blood–brain barrier disruption
BBB disruption is the moment in which penetration of the barrier by lymphocytes
occur and has been considered one of the early problems in MS lesions.
The BBB is compromised due to active recruitment of lymphocytes and monocytes
and their migration across the barrier.
Release of chemokines allow forthe activation of adhesion molecules on the
lymphocytes and monocytes, resulting in an interaction with the endothelial cells of
the BBB which then activate the expression of matrix metalloproteinases to
degrade thebarrier.
8
9. Clinical Manifestations
MS can affect any area of the brain, optic nerve, or
spinal cord, causing almostany neurologic symptom.
A classic MS sign: Uthoff’s phenomenon is
a worsening of symptoms in theheat.
Symptoms of relapse tendto:
• Developovera few days
• Stabilize for a fewweeks
• Improveoverweeksor months
• Be followed bya period of stability (a
remission)
9
10. 1. Blurredvision
2. Unilateral loss ofvision
3. Oscillopsia
4. Diplopia
Motor
1. Trunk/limbweakness
2. Spascity
3. Hyperreflexia
4. Gaitdisturbance
5. Balanceproblems
Signs & Symptoms Consistent with Demyelinating Disease
Visual Sensory
1. Numbness
2. Paresthesias
3. Dysesthesias
4. L’Hermitte’s sign (electrical sensations run
down the spine when the patient bends her
headforward)
5. “MS Hug” (tightening
around thechest)
6. Trigeminal neuralgia
7. Proprioception deficits
10
12. Diagnostics
MRI (Magnetic Resonance Imaging) is used in diagnosing Multiple
Sclerosis, but it should notbe used as the only diagnostictest.
Other useful tests include cerebrospinal fluid via spinal tap orlumbar puncture.It commonly
shows a mild lymphycytosis or a slightlyincreased protein.CSF protein electrophoresis shows the
presence of discrete bands in the immunoglobulin G (IGG) region (oligoclonal bands).
For a diagnosis of primary progressive MS,an abnormal CSF finding with evidenceof
inflammation and immune abnormalityis necessary*
12
13. Classification & Prognosis
MS is classified into 4types:
1-Benign Multiple Sclerosis :
• Mild infrequent sensory exacerbations with fullrecovery.
2-Relapsing Remitting Multiple Sclerosis:
• Episodes of exacerbations and remissions during which not all symptoms resolve
completely. The patient may be left with permanent disability which may vary in
severity. relapses are often more severe than in the previous group. Relapsesalso
become more severewith time.
13
14. 3-Secondary ChronicProgressive
• Condition of patients with relapsing/remitting disease begins to gradually worsen
over time with resulting accumulation of neurologic signs and symptoms. In this
form of the disease, relapses become more severe while remissions are less
complete, shorter in duration, and eventually non-existent. The course of MS
becomes steadilyprogressive.
4-Primary Progressive
• There is no history of relapse in these
patients. Disease begins with aslow
progression of neurologic deficits.
Problems appear and gradually worsen
over time.
14
16. Most effective treatment
OCRELIZUMAB
Ocrelizumab is an experimental drug which is being tested for the treatment of
relapsing remitting and primary progressive MS.
• In relapsing remitting MS, ocrelizumab reduced relapse rates by approximately
50% compared to beta interferon
• In primary progressive MS, ocrelizumab reduced 12 week disability progression
by 24% compared to placebo
16
17. • Ocrelizumab is a monoclonal antibody to target a marker (anti-CD20)
on the surface of B cells, a type of white blood cell (lymphocyte) which
is thought to influence the abnormal immune response that attacks the
myelin surrounding nerve cells. Targeted B cells are destroyed.
MECHANISM OF ACTION
17
19. Relapsing remitting MS
• In a phase II, 24 week, clinical trial, 218 people were split into
groups receiving one of two doses of ocrelizumab (600mg
and 2000mg), interferon beta-1a (Avonex) or placebo. After
24 weeks, the number of active lesions as measured by MRI
scans was 89% lower in the low dose group and 96% lower
in the high dose group compared with the placebo group.
Phase II Experimental study
19
20. The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in
multiple sclerosis and monitoring changes in the level of disability over time.
20
21. • Primary progressive MS
• Oratorio - ocrelizumab compared to placebo
• This phase III study recruited 732 participants with primary progressive MS and EDSS
of 3 to 6.5 who took either 600mg ocrelizumab or placebo by iv infusion every 6
months for more than 2 years.
Phase III experimental study
21
22. • Reduction of disability, compared to placebo.
– 24% MS patients less likely to have an increase in their disability than those taking placebo.
• After 120 weeks of treatment, increased walking speed over 25 feet
• 39% slow walkers for ocrelizumab compared to 55% slow for placebo.
• Brain lesion volume decreased by 3.4% with ocrelizumab and increased by 7.4%
with placebo. Loss of brain volume was 0.9% for ocrelizumab and 1.09% for
placebo.
Results
22
23. • In May 2017, a first case of progressive multifocal leukoencephalopathy (PML) was
reported in a person taking ocrelizumab.
• Infusion-related reactions, herpes (oral herpes and shingles)
• Neoplasms including several cases of breast cancer, were reported
• Ocrelizumab has previously been investigated as a treatment for rheumatoid
arthritis but studies were discontinued because of a high incidence of
opportunistic infections in participants.
ADVERSE EFFECTS
23
24. • Tysabri is a disease modifying drug (DMD)
for very active relapsing remitting MS.
• MECHANISM OF ACTION
• When inflammatory cells such as T-
lymphocytes pass through the BBB through
interaction with receptors on the endothelial
cells. Natalizumab appears to reduce the
transmission of immune cells into the CNS by
interfering with the α4β1-integrin receptor
molecules on the surfaces of cells. The effect
appears to occur on endothelial cells
expressing the VCAM-1 gene.
Natalizumab's mechanism of action is
believed to be the prevention of immune cells
from crossing blood vessel walls to reach
affected organs.
Most effective treatment
Natalizumab (Tysabri)
24
25. • Evidence for the effectiveness of Tysabri has come from a large clinical trial.
• AFFIRM - Tysabri compared to placebo
• This two year study compared Tysabri with placebo in 942 people with relapsing
remitting MS.
• Tysabri reduced the number of relapses by 68% compared to placebo.
• People taking Tysabri were less likely to experience worsening of their disability.
After two years, 29% of the placebo group showed at least a one-point increase in
the Expanded Disability Status Scale (EDSS), compared to 17% of the Tysabri group.
• Tysabri has also been investigated as a treatment for secondary progressive MS
where increasing disability is not the result of relapses.
Tysabri clinical trial
25
26. • Increased risk of progressive multifocal leukoencephalopathy
(PML), an uncommon brain infection that can lead to severe disability or even
death. PML is caused by a mutation of the JC virus, a common infection
completely unrelated to MS. It is normally kept under control by the immune
system, causing no problems.
If your immune system is weakened and your body less able to fight an infection, which may occur when taking Tysabri, the
JC virus can become active and cause inflammation and damage to the brain.
ADVERSE EFFECTS
26
27. • Common (affecting more than 1 person in 100)
• urinary tract infections
• inflammation of the nose
• shivering
• itchy rash (urticaria)
• headache
• dizziness
• nausea, vomiting
• joint pain
• fever
• Less common side effects (affecting less than 1 person in 100)
• severe allergic reaction during infusion (rash, swelling of face, lips or
tongue,difficulty breathing)
• discomfort during the infusion including feeling sick, headache, dizziness
• progressive multifocal leukoencephalopathy (PML)
• serious infections
• liver problems
ADVERSE EFFECTS
27
28. • Lemtrada is a disease modifying drug for active relapsing remitting MS and
for very active relapsing remitting MS. You have fewer relapses than you might
have had without treatment.
• Lemtrada may also slow down the build-up of disability associated with MS.
• Mechanism Of Action
• Anti-CD52 monoclonal antibody directed against the lymphocytes that are
involved when the immune system attacks myelin. It is thought that the immune
cells which grow back after treatment do not cause damage to nerves.
Most effective treatment
Alemtuzumab (Lemtrada)
28
29. • Evidence for the effectiveness Lemtrada
CARE-MS I CARE-MS II
TWO YEARS STUDY
Lemtrada compared to Rebif
581 people who had not been treated
with a DMD
667 people who had had at least one
relapse while taking a DMD.
Lemtrada reduced relapses by 55%
compared to Rebif
It reduced relapses by 49% compared to
Rebif. The risk of disease progression
was also reduced by 42% compared to
Rebif, with 20% of the Rebif group
showing an increase in disability
compared to 13% of the Lemtrada
group.
29
30. • infusion-related reactions such as headache, rashes, fever and nausea.
• infections including coughs, colds, chest infections and herpes virus infections (such as
cold sores or shingles)
• To reduce the risk of herpes infections, an antiviral medication should be taken starting
from the first day of infusion and continued for at least one month
ADVERSE EFFECTS
30
31. • Three serious side effects have been reported from clinical trials
• Overactive or underactive thyroid gland leading to thyroid disorders
• Idiopathic thrombocytopenic purpura (ITP), a serious disorder which prevents
blood from clotting
• Kidney problems
• These side effects are treatable if caught early enough. People taking Lemtrada will
be informed of the early signs and symptoms of these side effects.
31
32. • Common side effects (affecting more than 1 person in 100)
• infusion associated reactions including headaches, rashes, fever and nausea
• infections - respiratory and urinary
• decrease in white blood cells (lymphopenia)
• changes in blood pressure, heart rate
• rash
• musculoskeletal pain
32
33. Highly Effective Therapy
Fingolimod (Gilenya )
• Gilenya is a disease modifying drug for relapsing remitting MS.
• In clinical trials people taking Gilenya had about 50% fewer relapses than people
taking placebo. MRI scans showed that fewer, smaller or no new areas of active
MS (lesions).
• Gilenya may also slow down the build-up of disability associated with MS.
33
34. • Mechanism Of Action
• Fingolimod…
• is the first agent in the class of small molecules SIP-R agonists
• reduces the recirculation of lymphocytes into lymphonodes by binding to their
surface in the blood. Lymphocytes are then trapped in the lymph glands,
preventing them from crossing BBB and reach the central nervous system.
34
35. • Common side effects include increased risk of infections, cough, headache, back
pain, diarrhoea and increased liver enzyme levels.
• Gilenya may also cause a less common side effect (affecting less 1 in 100 people)
macular oedema, a swelling in the back of the eye which can affect vision.
• Cases of basal cell carcinoma, a kind of skin cancer, have been reported in people
taking Gilenya. Basal cell carcinoma is a slow-growing skin cancer that almost never spreads to other parts of the
body or becomes life-threatening but can be disfiguring if not treated promptly.
ADVERSE EFFECTS
35
36. • Common side effects (affecting more than 1 person in 100)
• headache
• back pain
• diarrhoea
• cough
• raised liver enzyme levels
• infections: herpes virus, fungal, flu
• changes in heartbeat
• dizziness, weakness
• lowering of white blood cells
• skin rash, itching
• depression
• eye pain, blurred vision
• mild increase in blood pressure
• basal cell carcinoma
• Less common side effects (affecting less than 1 person in 100)
• pneumonia
• swelling in the back of the eye (macular oedema)
• low mood
• lowering of neutrophils (type of white blood cell)
36
37. • Tecfidera is a disease modifying drug (DMD) for relapsing remitting MS.
• It reduces the number of relapses by about one half (50%), compared to taking
placebo.
Highly Effective Therapy
Dimethylfumarate DMF (Tecfidera)
37
38. • DMF decreases absolute lymphocyte counts. CD8+ T-cells are the most
profoundly affected, but reduction also occurs in the CD4+ population,
particularly within the pro-inflammatory T-helper Th1 and Th17 subsets,
• reducing the inflammation caused when the immune system attacks myelin,
resulting in less damage to myelin
• protecting nerve cells from the damage caused by chemicals released during
the immune attack
Mechanism of Action
reduction in CD8+
and to lesser
extent CD4+ T-
cells, CD19 B cells
Th1 and Th17 decrease, shifting
the balance toward more anti-
inflammatory Th2, T-regulatory
and B-regulatory subsets
In CNS
DMF activators of the
Nrf2-dependent
pathway, which
protects neurons from
oxidative stress. Nrf2
increase transcription
of genes encoding
antioxidant enzymes
Front Neurol. 2018;9:5. doi: 10.3389/fneur.2018.00005
38
39. • Flushing and feeling hot
• Gastrointestinal upset - diarrhoea, feeling sick, stomach pains
• In clinical trials changes in liver and kidney function were
reported. Regular blood and urine tests are recommended to
monitor for possible effects.
ADVERSE EFFECTS
• Common side effects (affecting more than 1 person in 100)
• flushing and feeling hot
• gastrointestinal upset (feeling sick, diarrhoea, abdominal pain, vomiting,
indigestion)
• decrease in white blood cells
• rash
• increased levels of liver enzymes
• ketones and protein in urine
39
40. Compared to placebo,
Tecfidera twice daily
reduced the number of
relapses in one year by
53%. Also reduced the risk
of 3 month disability
progression by 38%.
2 year study
compared Tecfide
ra taken either 2
or 3 times daily
and placebo in
more than 1,200
participants with
RRMS.
DEFINE - Tecfidera
compared to placebo
Evidence for the effectiveness of Tecfidera has come from two
large clinical trials.
40
41. • CONFIRM - Tecfidera or Copaxone compared to placebo
• This two year study with 1,232 participants was similar to DEFINE, but with an
additional group who took Copaxone (glatiramer acetate) for comparison.
• Tecfidera reduced the number of relapses in one year by 44% for the twice-daily
dose compared to placebo. In contrast, Copaxone reduced the number of relapses
by 29% compared to placebo.
• The reduction in disability progression observed in the DEFINE study was not seen
in the CONFIRM study.
41
42. Moderately Effective Therapy
Beta Interferons
These are treatments for relapsing MS. They have the following brand names:
• Avonex, Betaferon
Mechanism Of Action
• Interferons (IFN) are endogenous cytokines that modulate transcription of hundred of genes
involved in inflammatory responses
• Interferon beta balances the expression of pro- and anti-inflammatory molecules in the brain
• In vitro, interferon beta reduces production of Th17 cells which are a subset of T lymphocytes that
seem to have a role in the pathophysiology of MS
• IFN can reduce (and might prevent) the inflammation that damages nerves in MS.
Cell migration by
disturbing VLA4 and
VCAM1 receptor
interactions.
VLA expression on T cells.
Production of MMP
Soluble VCAM1
levels
42
43. • The effectiveness of beta interferons is classed as 'moderate'.
This is based on how much they reduce relapses and slow
down how fast people's disability gets worse.
• Relapses dropped by: 33%
• This means that in trials, on average, people saw a 33% drop
in the number of relapses they had. This was compared to
people who took a placebo, a dummy treatment with no drug
in it.
• Disability getting worse was slowed down by a modest
amount
Beta interferons can be injected
with a 'pen' that means there is
no need of needle
43
44. • After a beta interferon injection at least one in 10 people find they feel like they
have flu, with headaches, muscle aches, chills or a fever.
• Your skin can become red, hard, bruised or itchy where you inject. Beta interferons
might cause depression, so you might not be given one if you've had depression in
the past.
ADVERSE EFFECTS
44
45. • Copaxone is a disease modifying drug for relapsing remitting MS.
• It reduces the number of relapses by about one third (30%), compared to taking placebo.
• Who can take Copaxone?
• Copaxone can be prescribed for adults with active relapsing remitting MS.
• Conception and pregnancy
• Pregnancy is not recommended during treatment but this drug has the best profile for pregnant
woman with mild disease
Mechanism of action
• Promote the expansion of anti-inflammatory T-helper 2 and regulatory T cells, and induced the
release of neurotrophic factors.
Moderately effective
Glatiramer acetate (Copaxone)
45
46. .
• Common side effects (affecting more than 1 person in 100)
• injection site reactions
• lipoatrophy (indentations in the skin)
• headache
• depression, anxiety
• nausea
• feeling weak
• chest pain
• swollen lymph nodes
• gastrointestinal changes
• Less common side effects (affecting less than 1 person in 100)
• blood cell changes
• extra heartbeats
• thyroid changes
• dilation of blood vessels
• immediate post-injection reaction (IPIR)
ADVERSE EFFECTS
46
47. • Copaxone Clinical trial
• Copolymer 1 Multiple Sclerosis Study Group - Copaxone compared to
placebo
• 251 people with relapsing remitting MS took either Copaxone or placebo for 2
years.
• The main measure of the study was the number of relapses per year –
• Copaxone reduced this by 29% compared to placebo. People taking Copaxone had
improved or unchanged disability (measured as a 1 point change in EDSS) and
people taking placebo had worsened disability.
47
48. • GALA - Copaxone three times weekly compared to placebo
• 1404 people with relapsing remitting MS took either Copaxone three times weekly
or placebo for one year.
• Compared to placebo, Copaxone reduced relapses by 34%. MRI results showed
that Copaxone significantly reduced the number of lesions compared to placebo.
48
49. • Aubagio is a disease modifying drug for relapsing remitting MS
Mechanism of action
• Antiproliferative agent that acts as a pyrimidine synthesis inhibitor. In particular,
it inhibits a mitochondrial dehydrogenase, which is the key enzyme for the de novo
pyrimidine synthesis
• Teriflunomide inhibits rapidly dividing cells, including activated T cells, which are
thought to drive the disease process in MS.
Moderately Effective Therapy
Teriflunomide (Aubagio)
49
50. • teratogenic
• Common side effects (affecting more than 1 person in 100)
• increased levels of liver enzymes
• nausea and diarrhoea
• hair thinning and loss
• urinary tract infection
• inflammation of the nose and throat
• influenza
• pins and needles
• infections
• decrease in white blood cells (neutropenia)
• mild allergic reactions
• anxiety
• nerve pain
• decrease in red blood cells (anaemia)
• increase in blood pressure
• rash
• musculoskeletal pain
• Less common side effects (affecting less than 1 person in 100)
• decrease in blood platelets (thrombocytopenia)
• peripheral neuropathy
ADVERSE EFFECTS
50
51. TEMSO - Aubagio
compared to
placebo
TOWER - Aubagio
compared to
placebo
TENERE - Aubagio
compared to Rebif
Duration two year, double-
blind study
48 weeks two years
No. of People 1088 people with
relapsing remitting
MS
1169 people with
relapsing remitting
MS
324 people
Comparison comparing two doses
of Aubagio with
placebo
two different doses
of Aubagio or
placebo
two doses of
Aubagio with Rebif
(interferon beta 1a)
Result:
Drugs shows
reduction no. of
relapses
Drug shows
reduction of
disability progression
31%.
29.8%
36%.
31.5%.
No Change
No Change
Aubagio Experimental Study
51
52. • Managing relapses
• Treating relapses
• The options for managing an MS relapse are:
• treatment with high-dose steroids, either as an in-patient, a ‘day-case’ or at
home
• rehabilitation – after steroids, or without steroids being given
• no treatment
NICE says that: "The course should be started
as soon as possible after onset of the relapse
and should be either:
intravenous methylprednisolone, 1g daily, for
between 3 and 5 days or high-dose oral
methylprednisolone, 0.5g daily, for 5 days".
52
54. Social Stigma
Multiple sclerosis hasa profound impacton
patients’ social roles and the well-being of their
families.Varying degrees of functional decline
typically accompany MS. Because the onset is
usually at about 30 years of age, the lossin
productivity ofpeople.
Stigmatized individuals are often rejected by
neighbors and the community, and as a result
sufferlonelinessand depression.
54
55. OCCUPATIONAL THERAPY (OT) IN MS
Occupational therapy can help people with multiple sclerosis stay active in daily life.
By improving…
skills, teaching alternative ways to complete tasks, or introducing handy equipment
55
56. HOW CAN OT HELP?
By providing recommendations in the following areas:
Arm and hand therapy
Handwriting aids
Home modification information
Driver evaluation and vehicle modification information
Cooking and homemaking adaptations
Eating and dinnerware adaptations
Computer modifications
Workplace or work equipment modifications
Leisure skill development
Manual or electric wheelchair use
Bathtub and toilet equipment use
Dressing and grooming aids
56
57. • Speech therapy is a type of rehablitation that focuses on improving movement of
the mouth area. . Speech therapy may be part of a multiple sclerosis treatment
plan if weak facial muscle lesions (damaged areas in the brain) have affected your
abilty to talk or swallow
SPEECH THERAPY
Oral exercises Voice training
Special communication
devices
Diet modifications
Altered
positions while
eating
57
58. PHYSIOTHERAPY
• A physiotherapist works with people with MS to
assess physical difficulties and help improve
movement and other functions of the body. Exercise is
one of the key ways in which they do this.
58
59. Exercise training in MS
For many years patients with MS had been advised not to participate in physical
training but during the last decade it has been shown that worsening of the
number and/or intensity of sensory symptoms which is experienced by more than
40% of MS patients after exercise is temporal and will be normalized within an
hour after exercise cessation.
59
61. Individualized exercise in MS can promote many important therapeutic outcomes,
such as improved cardiorespiratory, muscle function, decreasing depression and
fatigue toward promotion of health and quality of life.
61
62. • Exercise is considered helpful in managing common symptoms and promoting
wellness, for reducing the risk of comorbidities such as obesity, heart disease,
diabetes and osteoporosis.
62
63. • Several studies have tested endurance training as an intervention suitable
to counteract the fatigue.
63
64. • Endurance training with low to moderate intensity (40-60 %VO2Max) is well
tolerated by MS patients too
• Improvements have been found in items regarding vitality, social functioning,
mood, energy, fatigue, anger, sexual function and depression.
64
65. It has been recommended a training frequency of two to three sessions per week
starting with (50-70% VO2 Max) with a starting duration of 10-40 min with interval
training using intensities of up to 90% of VO2- Max.
• In general is recommended that exercise program should be planned
which seeing performing before large muscles than small and multiple
joint before single and lower limbs should have the priority.
65
66. • Very little is known about combined training in MS patients but is possible assess
that is well tolerated if performed on alteranate days (two weekly days of
resistance training and two days of endurance training with an interval of 24-48
hours for recovery.
• Load-bearing exercise may stimulate mantainance of muscle mass sufficiently to
slow the progression of sarcopenia (loss of skeletal muscle mass) in MS and weight
bearing during ambulation will also likely decrease the severity of lower-extremity
osteopenia (protein and mineral content of bone tissue is reduced).
66
67. • Slow and gentle stretching techniques are recomended and flexibility exercise
should be performed by rhytmical, repetitive motion exercises with emphasis on
improving motor control using proprioceptive facilitation techniques..
• Prescribing exercise on an intermittent basis helps to avoid
excessive build-up of fatigue and heat stress, which worsen MS
symptoms
67
68. BENEFITS OF EXERCISE
?
?
Improve overall health of people with milder MS
Help people with more severe MS to stay as mobile
& active as possible
Help some people manage MS symptoms
and decrease the risk of heart disease
Improve muscle strength and fitness, helping
with mobility or weakness problems
Help manage weight control, especially
when combined with a healthy, well-
balanced diet
68
69. •
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• Further analyses of Oratorio reported at the 2016 ACTRIMS conference - 22 February 2016
• Montalban X, et al.Ocrelizumab versus placebo in primary progressive multiple sclerosis.New England Journal of Medicine 2017;376(3):209-
220.Summary
• Hauser SL, et al.Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosisNew England Journal of Medicine 2017;376(3):221-234
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Technology Appraisal Guidance 320Full guideline
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• Gold R, et al.Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis.New England Journal of Medicine
2012;367:1098-107
• Fox RJ, et al.Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis.New England Journal of Medicine
2012;367:1087-97.
• National Institute for Health and Care Excellence (NICE).Beta interferon and glatiramer acetate for the treatment of multiple
sclerosisNICE technology appraisal guidance TA32
• Johnson KP, et al.Copolymer 1 reduces relapse rate and improves disability in relapsing remitting multiple sclerosis: results of a phase
III multicenter, double-blind, placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group.Neurology 1995;45(7):1268-76.
• Khan O, et al.Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis.Annals of Neurology 2013;73(6):705-13.
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