Multiple Sclerosis: An Overview for Pharmacists

What does MS look like?

• Julia—a 35yo white married mother of 3 who is exhausted all the time and can’t drive because of vision problems and numbness in her feet

• Jackson—a 25yo African-American man who stopped working because he can’t control his bladder or remember what he read in the morning paper

• Maria—a 10yo Hispanic girl who falls down a lot and whose parents just told her she has MS

• Loretta—a 47yo white single woman who moved into a nursing home because she can no longer care for herself

What else does MS look like?

• Sam—a 45yo divorced white man who has looked and felt fine since he was diagnosed seven years ago

• Karen—a 24yo single white woman who is severely depressed and worried about losing her job because of her diagnosis of MS

• Sandra—a 30yo single mother of two who experiences severe burning pain in her legs and feet

• Richard—who was found on autopsy at age 76 to have MS but never knew it

• Jeannette—whose tremors are so severe that she cannot feed herself

1396: Earliest Recorded Case of MS

From Sister Lidwina to the present…

• 1868—Jean-Martin Charcot describes the disease and finds MS plaques (scars) on autopsy.

• 1878—Louis Ranvier describes the myelin sheath (the primary target of MS in the central nervous system).

“Multiple sclerosis is often one of the most difficult problems in clinical medicine.” (Charcot, 1894)

“When more is known of the causes and…pathology of the disease… more rational methods may brighten the

therapeutic prospect.” (Gowers, 1898)• 1981—1st MRI image of MS is published.

From Sister Lidwina to the present, cont’d

• 1993—The first disease-modifying agent for MS—Betaseron—is approved in the U.S.

• 1998—Bruce Trapp confirms that the nerve fibers themselves are irreversibly damaged early in the disease course (probably accounting for the permanent disability that can occur).

• 2009—Today, there are seven medications approved in the U.S. for the treatment of MS and more in the pipeline.

Today there are 400,000 people with MS in the U.S. and 2.5 million worldwide.

What MS Is:

• MS is thought to be a disease of the immune system—perhaps autoimmune.

• The immune system attacks the myelin coating around the nerves in the central nervous system (CNS—brain, spinal cord, and optic nerves) and the nerve fibers themselves.

• Its name comes from the scarring caused by inflammatory attacks at multiple sites in the central nervous system.

What MS Is Not:

• MS is not: Contagious Directly inherited Always severely disabling Fatal—except in fairly rare instances

• Being diagnosed with MS is not a reason to: Stop working Stop doing things that one enjoys Not have children

What Causes MS?

GeneticPredisposition

EnvironmentalTrigger

Immune Attack

Loss of myelin & nerve fiber

What happens in MS?

...cross the blood-brain barrier…

…launch attack on myelin & nerve fibers...

“Activated” T cells...

…to obstruct nerve signals

myelinated nerve fibermyelinated nerve fiber

What happens to the myelin and nerve fibers?

What are possible symptoms?

Cognitive difficulties (memory, attention, processing)

Pain (neurogenic) Heat sensitivity Spasticity Gait, balance, and

coordination problems Speech/swallowing

problems Tremor

Fatigue (most common) Decreased visual acuity,

diplopia Bladder and/or bowel

dysfunction

Sexual dysfunction Paresthesias (tingling,

(numbness, burning) Emotional disturbances

(depression, mood swings)

MS symptoms vary between individuals and are unpredictable

How is MS diagnosed?

• MS is a clinical diagnosis: Signs and symptoms Medical history Laboratory tests

• Requires dissemination in time and space: Space: Evidence of scarring (plaques) in at least two

separate areas of the CNS (space) Time: Evidence that the plaques occurred at different

points in time • There must be no other explanation

What tests may be used to help confirm the diagnosis?

• Magnetic resonance imaging (MRI)

• Visual evoked potentials (VEP)

• Lumbar puncture

What is a clinically-isolated syndrome (CIS)?

• First neurologic episode caused by demyelination in the CNS

• May be monofocal or multifocal• May or may not go on to become MS

CIS accompanied by MS-like lesions on MRI is more likely to become MS than CIS without lesions on MRI

• Interferon medications delay second episode Avonex, Betaseron, Extavia, Copaxone approved

for this use Rebif has demonstrated its effectiveness

Who gets MS?

• Usually diagnosed between 20 and 50 Occasionally diagnosed in young children and

older adults• More common in women than men (2-3:1)• Most common in those of Northern European ancestry

More common in Caucasians than Hispanics or African Americans; rare among Asians

• More common in temperate areas (further from the equator)

What is the genetic factor?

• The risk of getting MS is approximately: 1/750 for the general population (0.1%) 1/40 for person with a close relative with MS (3%) 1/4 for an identical twin (25%)

• 20% of people with MS have a blood relative with MS

The risk is higher in any family in which there are several family members with the disease (aka multiplex families)

What is the prognosis?

• One hallmark of MS is its unpredictability. Approximately 1/3 will have a very mild course Approximately 1/3 will have a moderate course Approximately 1/3 will become more disabled

• Certain characteristics predict a better outcome: Female Onset before age 35 Sensory symptoms Monofocal rather than multifocal episodes Complete recovery following a relapse

What are thedifferent patterns (courses) of MS?

• Relapsing-Remitting MS (RRMS)• Secondary Progressive MS (SPMS)• Primary Progressive MS (PPMS)• Progressive-Relapsing MS (PRMS)

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An Overview of Treatment Strategies

Who is on the MS “Treatment Team”?

• Neurologist• Urologist• Nurse• Physiatrist • Physical therapist• Occupational therapist• Speech/language

pathologist

• Psychiatrist• Psychotherapist• Neuropsychologist• Social worker/Care

manager• Pharmacist

What are the treatment strategies?

• Gone are the “Diagnose and Adios” days of MS care• Management of MS falls into five general categories:

Treatment of relapses (aka exacerbations, flare-ups, attacks—that last at least 24 hours)

Symptom management Disease modification Rehabilitation (maintain/improve function)

Psychosocial support

How are relapses treated?

• Not all relapses require treatment Mild, sensory sx are allowed to resolve on their own. Sx that interfere with function (e.g., visual or walking

problems) are usually treated• 3-5 day course of IV methylprednisolone—with/without an oral

taper of prednisone High-dose oral steroids used by some neurologists

• Rehabilitation to restore/maintain function• Psychosocial support

How is the disease course treated?

• Ten disease-modifying therapies are FDA-approved for relapsing forms of MS: interferon beta-1a (Avonex® and Rebif®) [inj.] interferon beta-1b (Betaseron® and Extavia®) [inj.] glatiramer acetate (Copaxone®) [inj.] fingolimod (Gilenya™) [oral] teriflunomide (Aubagio®) [oral] Dimethyl fumarate (Tecfidera™ natalizumab (Tysabri®) [inf] mitoxantrone (Novantrone®) [inf]

What do the disease-modifying drugs do?

• All reduce attack frequency and severity, reduce scarring on MRI, and probably slow disease progression.

• These medications do not: Cure the disease Make people feel better Alleviate symptoms

How important is early treatment?

• The Society’s National Medical Advisory Committee recommends that treatment be considered as soon as a dx of relapsing MS has been confirmed. Irreversible damage to axons occurs even in the

earliest stages of the illness. Tx is most effective during early, inflammatory phase Tx is least effective during later, neurodegenerative

phase• No treatment has been approved for primary-progressive

MS.

Approximately 60% of PwMS are on Tx

What factors affect treatment adherence?

• Patient readiness is key• Factors affecting readiness include:

Lack of knowledge about MS Denial of illness Unrealistic expectations of treatment outcomes Side effects Cultural factors Lack of support (medical team, family) Distrust of medical community and/or prescription

medications

Treatment Challenges in MS Research

• Current therapies—primarily anti-inflammatory• Future therapies

Design selective therapies that target very specific components of the immune system

Utilize combination of strategies: Anti-inflammatory Neural repair Neuroprotection

New Treatments on Horizon

• Enhancement of Existing Therapies• Potential Therapies

Oral• estrogens/testosterone• laquinimod

Parenteral• rituximab (Rituxan)• alemtuzumab (Lemtrada)• declizumab (Zenapax)• dirucotide

Managing MS Symptoms

• Symptom management begins on Day 1 and continues throughout the disease course.

• Symptom management is an art.• Virtually every medication used to treat MS symptoms is

used off-label.• Effective symptom management involves medication,

rehabilitation strategies, emotional support—and good coordination of care.

Managing MS Fatigue

• > 80% of people with MS experience fatigue; many identify it as their most disabling

• Along with cognitive dysfunction, fatigue is the most common cause of early departure from the workforce

• MS fatigue is easily misunderstood by family members and employers as laziness or disinterest

• MS fatigue is multi-faceted

Managing MS Fatigue, cont’d

• Identify/address contributory factors Disrupted sleep; muscle fatigue; disability-related

fatigue; depression; medications• Develop comprehensive treatment plan

Medications: amantadine; modafinil Energy management: planning/prioritizing; mobility aids Exercise regimen

Managing Bladder Dysfunction

• > 75% of people with MS will experience bladder problems.• Bladder dysfunction is a major cause of morbidity,

embarrassment, and social isolation.

Managing Bladder Dysfunction

• Storage dysfunction Small, spastic bladder in which small quantity of urine

triggers the urge to void Sx include: urgency, frequency, incontinence, nocturia Tx includes: anticiholinergic/antimuscarinic medication

• Emptying dysfunction Bladder fails to empty risk of UTI Sx include: urgency, frequency, nocturia, incontinence Tx

includes: ISC and anticholinergic/antimuscarinic medications

Managing Bowel Problems

• Experienced by 50% of people with MS Constipation—most common

• “Diarrhea” (related to impaction) Bowel incontinence—least common

• Managed best with regular bowel routine Adequate fluid/fiber intake Exercise OTC products as needed Anticholinergic medications added to

manage incontinence

Managing Spasticity (increased muscle tone)

• Experienced by 40-60% of people with MS (more common in the lower extremities)

• Management strategies: Stretching Oral medication (baclofen, tizanidine, clonazapam,

gabapentin, cyproheptidine, dantrolene, dopaminergic agonists

Baclofen pump Botox injections; nerve blocks; surgery

• Some spasticity is useful to counteract weakness

Managing Primary Sexual Dysfunction

• 40-80% of men and women with MS Reduced libido (behavioral/environmental strategies) Sensory disturbances (anticonvulsant medications) Anorgasmia (body-mapping exercises)

• Women Reduced lubrication (gels)

• Men Erectile dysfunction (pharmacotherapy;

implants)

Managing Secondary/Tertiary Sexual Dysfunction

• Secondary dysfunction (other contributory factors) Managing MS symptoms that interfere with sexual

activity/pleasure (fatigue, spasticity, etc.) Managing medications to promote sexual comfort and

responsiveness (anticholinergics; antidepressants, fatigue and spasticity meds)

• Tertiary dysfunction (feeling; attitudes)• Education; counseling

Managing Cognitive Dysfunction

• Occurs in 50-60% of people with MS• Ranges from relatively mild to quite severe• Correlates with number of lesions and lesion area on MRI, as well

as brain atrophy• Can occur at any time but is more common later in the disease• Can occur with any disease course, but is slightly more likely in

progressive MS.• Being in an exacerbation is a risk factor for cognitive dysfunction.• Most common problems: memory; attention/concentration;

information processing • Treatments:

Disease-modifying therapy to prevent relapses Cognitive rehabilitation: primarily compensatory

Managing Depression

• >50% of people with MS will experience a major depressive episode.

• Suicide in MS is 7x higher than in the general population. Greatest risk factor for suicide in MS is depression.

• Depression is under-recognized, under- diagnosed and under-treated in MS

• Recommended tx = psychotherapy + medication + exercise

Managing Pain

• 75% of people with MS experience pain• Neuropathic (central) pain

Paroxysmal pain (trigeminal neuralgia; headache)• Anticonvulsants

Continuous pain (dysesthesias)• Tricicyclics; anticonvulsants

• Nociceptive (secondary) pain Musculskeletal pain

Physical therapy; NSAIDs

Spasticity—As described previously

Managing Ataxia/Tremor

• Incidence is unknown• Potentially severely disabling• No effective treatments at this time

Medications that may be tried:• propranolol; primidone; acetazolamide; buspirone;

clonazepam Occupational therapy

• Weighting; assistive devices Thalamic surgery for tremor (generally poor results)

Serious Complications

• Urosepsis• Aspiration pneumonia• Pulmonary dysfunction• Skin breakdown• Untreated depression• Osteoporosis

What can people do to feel their best?

• Balance activity with rest.• Talk with their doctor about the right type/amount of

exercise for them.• Eat a balanced low-fat, high-fiber diet.• Avoid heat if they are heat-sensitive.• Drink plenty of fluids to maintain bladder health and

avoid constipation.• Follow the standard preventive health measures

recommended for their age group

What else can people do to feel their best?

• Reach out to their support system; no one needs to be alone in coping with MS.

• Stay connected with others; avoid isolation.• Become an educated consumer.• Make thoughtful decisions regarding:

Disclosure Choice of physician Employment choices Financial planning

• Be aware of common emotional reactions.

The Allure of CAM

Understanding CAM’s Allure

• MS treatments are only partially effective.• Personal testamonials are extremely powerful.• Many people believe “Safe…natural…healthy…effective…”

and distrust the effects of mainstream medicine. • It feels good to “take charge” of a chronic, unpredictable disease.

The Use of Complementary and Alternative Medicine (CAM) in MS

• Used by 50-88% of people with MS, generally in conjunction with conventional treatments

• Practitioners optimize the placebo effect• Recommendations to patients from Allen Bowling, MD,

PhD Consider conventional medicine first Learn about effectiveness, safety, cost Discuss it with your physician Use caution (“buyer beware”) Remember: MS involves excessive immune activity;

no need to “boost” immune system”

Bowling AC. Complementary and Alternative Medicine in Multiple Sclerosis (2nd ed.).

New York: Demos Medical Publishing, 2007

Possibly Beneficial CAM Interventions

• Diet low in saturated fat and enriched in polyunsaturated fatty acids (may suppress immune system)

• Acupuncture: anxiety, bladder; depression; pain; sleep• Massage: anxiety, pain, depression; pain; spasticity• Meditation: anxiety, pain, depression, pain• Exercise (T’ai chi; yoga): fatigue; anxiety, depression; weakness; walking• Cooling: fatigue; spasticity; walking• Biofeedback: anxiety; pain; sleep; bladder

Bowling AC. Complementary and Alternative Medicine in Multiple Sclerosis (2nd ed.).

New York: Demos Medical Publishing, 2007

Dietary Supplements to be Avoided

• Alfalfa• Ashwagandha• Astragalus• Cat’s claw• Garlic• Licorice• Melatonin

• Oligomeric proanthocyanidins

• Pycnogenol• Saw palmetto• Selenium• Stinging nettle• Vitamin A• Zinc

Supplements that may stimulate the immune system:

Bowling AC. Complementary and Alternative Medicine in Multiple Sclerosis (2nd ed.).

New York: Demos Medical Publishing, 2007

So what do we know about MS?

• MS is a chronic, unpredictable disease • The cause is still unknown• MS affects each person differently; symptoms vary widely• MS is not fatal, contagious, directly inherited, or always

disabling• Early diagnosis and treatment are important

Significant, irreversible damage can occur early on Available treatments reduce the number of relapses and may

slow progression• Treatment includes: attack management, symptom management,

disease modification, rehab, emotional support

NMSS Resources for Patients and Families

• 40+ chapters around the country• Web site (www.nationalmssociety.org)• Access to information, referrals, support (1-800-344-4867)• Educational programs (in-person, online)• Support programs (self-help groups, peer and professional

counseling, friendly visitors) • Consultation (legal, employment, insurance, long-term care)• Financial assistance

Society Resources for Professionals

• MS Clinical Care Network Website: www.nationalMSsociety.org/MSClinicalCare

Email: healthprof_info@nmss.org

Comprehensive MS library/literature search services

Clinical consultations with MS specialists Professional publications Professional education programs (medical,

rehab, nursing, mental health) Consultation on insurance and long-term care

issues