Pha 416 Multiple Sclerosis

Front 1

What is Multiple Sclerosis?

Back 1

Multiple Sclerosis (MS) is a chronic neurologic disease characterized by plaques or scars in the central nervous system as a result of the demyelination and atrophy of neuronal axons.

Front 2

What age is MS usually dx?

Back 2

20-40 years of age

Front 3

Explain the effect of demyelination on action potential.

Back 3

Loss of myelination leads to slowing of nerve conduction along the axons.

Front 4

Genetic Factors

Back 4

Incidence in 1st degree relatives is 20X higher than general population
Twin studies
Dizygotic twins
Monozygotic twins
No specific gene(s)
MHC molecules

Front 5

Autoimmune Dysfunction in MS

Back 5

Anti-myelin antibodies
Super antigenic stimulation of T cells

Front 6

Criteria for a Definite Diagnosis

Back 6

Two or more episodes (exacerbations) separated by time
Involvement of two or more systems
MRI

Front 7

What are the MS disease Subtypes?

Back 7

Relapsing Remitting (85% at onset)
Primary-progressive (10%)
Secondary-progressive(up to 76% of relapsing remitting )
Progressive-relapsing (5%)

Front 8

MS Symptoms

Back 8

Gait disturbances
Sensory complaints (numbness, paresthesia, pain)
Visual problems including double vision
Fatigue
Lack of coordination
Bladder and bowel problems
Sexual dysfunction
Depression
Mild cognitive impairment most noticeably short term memory loss
Partial or complete paralysis in severe cases.
Initial symptoms often include optic neuritis.
Optic neuritis and sensory symptoms usually progress more slowly than motor problems

Front 9

Tools for Evaluating Disability

Back 9

Kurtzke Expanded Disability Status Scale
Multiple Sclerosis Functional Composite (MSFC)

Front 10

Characteristics of Transitional MS

Back 10

5 to 10 years post diagnosis
EDSS score >3.5
Poor response to corticosteroids or low-dose interferons
Greater burden of disease on MRI
Higher recent relapse activity rate

Front 11

What does progression really mean?

Back 11

Life expectancy
Prior to the advent of current therapies, 50% of those with MS were wheel chair bound 15 years after diagnosis.
Suicide rate

Front 12

Pharmacologic Treatment for MS

Back 12

Treatment for acute relapses
Treatment to delay or shorten exacerbations
Symptomatic treatment

Front 13

Treatment of Acute Episodes

Back 13

Prednisone and methylprednisolone
Oral prednisone for mild attacks
(1mg/kg/day) with taper.
Solu-Medrol (methylprednisolone) for severe episodes
500-1000 mg/day IV for 3-5 days.
Usually followed by oral prednisone taper.

Front 14

A patient with MS has a mild attack which drug should be used for treatment?

Back 14

Oral prednisone - 1 mg/kg/day with taper.

Front 15

A patient with MS has a severe episode which drug should be used for treatment?

Back 15

Solu-Medrol (methylprednisolone) for severe episodes
500-1000 mg/day IV for 3-5 days.
Usually followed by oral prednisone taper.

Front 16

Approved Treatment

Back 16

Older drugs:
Avonex® or Rebif® (IFN-b-1a)
Betaseron® (IFN-b-1b)
Copaxone® (Glatiramer acetate)

Newer drugs:
Tysabri® (Natalizumab)
Gilenya® (Fingolimod)
Aubagio® (Teriflunomide)
Tecfidera® (Dimethyl fumarate

Front 17

The Interferons

Back 17

Avonex or IFN-b-1a is given as an IM injection once a week

Betaseron or IFN-b-1b is given as a subcutaneous injection every other day.

Front 18

What is a common side effect of using the interferons (Avonex or Betaseron)?

Back 18

Flu like symptoms (local site inflammation)

Front 19

Glatiramer acetate (Copaxone®)

Back 19

Structural similarity to myelin protein
May interfere with T-cell activity
20 mg daily subcutaneous injection
Numerous adverse effects
CV, CNS, GI, Neuromuscular, Dermatologic, Respiratory, Local
Usually self-limiting

Front 20

Natalizumab (Tysabri®)

Back 20

Inhibits movement of T-Cells into CNS
Once a month
69% reduction in relapses
65% reduction in hospitalizations
Fatigue, allergic reactions
PML (In JC virus positive patients)

Front 21

Fingolimod (Gilenya®)

Back 21

First oral agent for the treatment of RRMS
Approved in September 2010
Sphingosine-1-phosphate receptor modulator
Decreases lymphocytes in the circulation and CNS
0.5 mg every day
Lower relapse rate and fewer brain lesions compared to interferon β-1a

Front 22

Adverse effects of Fingolimod

Back 22

First and second degree heart block
Observe patient after first dose
Use with caution in patients taking anti-arrhythmic
Elevated liver transaminases
Macular edema
Viral infections

Front 23

Teriflunomide (Aubagio®)

Back 23

FDA approved in Sept. 2012
7 or 14 mg orally daily
Reduces T- and B-cell activation, proliferation and function
Immune surveillance is preserved

Front 24

Adverse effects of Teriflunomide

Back 24

Nausea, diarrhea, hair thinning

Front 25

What black box warning does Teriflunomide have?

Back 25

hepatotoxicity and pregnancy

Front 26

Dimethyl Fumarate (Tecfidera®)

Back 26

FDA Approved YESTERDAY
Reduces oxidative stress
Decreases demyelination
240 mg PO BID
Decreased annual relapse rate 44% vs. placebo
Copaxone decreased ARR 29% vs. placebo
Decreased new MRI lesions 71% vs placebo
Copaxone decrease lesions 54% vs. placebo

Front 27

What is the MOA of Tecfidera?

Back 27

Reduces oxidative stress - decreases demyelination

Front 28

Adverse effects of Dimethyl Fumarate.

Back 28

Flushing and GI complaints most common
Lymphocytopenia
Decreased by ~30% in the first year then stabilizes
Still within normal limits
No increases in infection

Front 29

Treatment for Progressive MS

Back 29

Mitoxantrone
Anti-proliferative effects
Decreases B-cells, T-cells, macrophages
Immunomodulation
Decrease antigen presentation
Decrease cytokine production
12 mg/m2 IVP every three months
Do not exceed 140 mg/m2 cumulative lifetime dose
Cardiac toxicity

Front 30

Mitoxantrone Effects

Back 30

Slows progression
Decreases treated relapses
Decreases CNS lesions

Front 31

Symptomatic Therapies: Fatigue

Back 31

Fatigue is the most common complaint in patients with MS
Amantadine

Front 32

Symptomatic Therapies: Vertigo

Back 32

Vertigo is a relatively common with symptoms that may last hours or days at a time.
Meclizine, low dose diazepam, and promethazine hydrochloride.
Nausea associated with vertigo may respond to metoclopramide

Front 33

Symptomatic Therapies: Muscle Spasms

Back 33

Frequent problem in the extensor muscles of lower limbs.
Baclofen
muscle weakness
increased fatigue
Subcutaneous pumps
Diazepam

Front 34

Symptomatic Therapies: Depression

Back 34

Severe mood swings and depression
SSRI’s or tricyclic anti-depressants are useful in treatment
Suicide rate for MS is 7.5X higher than general population

Front 35

Symptomatic Therapies: Urinary Tract

Back 35

Urgency, frequency and incontinence.
Anticholinergic drugs
oxybutynin
propantheline.
Baclofen or amitriptyline are potential choices if spasticity related.
Self catheterization
UTIs

Front 36

Symptomatic Therapies: Sexual Dysfunction

Back 36

Erectile dysfunction
For women, treatment of muscle spasms and pain may be the major issues.

Front 37

Symptomatic Therapies: Pain

Back 37

Pain is more common than originally expected.
May be responsible for some of depression associated with MS
most common in lower extremities
Carbamazepine, phenytoin or tricyclic antidepressants .
Gabapentin may be helpful.

Front 38

True or false: The opioiods are not effective for pain associated with MS?

Back 38

True