Multiple Sclerosis An Overview for Pharmacists What does

Multiple Sclerosis: An Overview for Pharmacists

What does MS look like? • Julia—a 35 yo 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 25 yo African-American man who stopped working because he can’t control his bladder or remember what he read in the morning paper • Maria—a 10 yo Hispanic girl who falls down a lot and whose parents just told her she has MS • Loretta—a 47 yo 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 45 yo divorced white man who has looked and felt fine since he was diagnosed seven years ago • Karen—a 24 yo single white woman who is severely depressed and worried about losing her job because of her diagnosis of MS • Sandra—a 30 yo 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 therapeutic prospect. ” (Gowers, 1898) • 1981— 1 st 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 considered an immune-mediated disease — 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? Genetic Predisposition Environmental Trigger Immune Attack Loss of myelin & nerve fiber

What happens in MS? “Activated” T cells. . . cross the blood-brain barrier… …launch attack on myelin & nerve fibers. . . …to obstruct nerve signals myelinated nerve fiber

What happens to the myelin and nerve fibers?

What are possible symptoms? · MS symptoms vary between individuals and are unpredictable § § § Fatigue (most common) Decreased visual acuity, diplopia Bladder and/or bowel dysfunction Sexual dysfunction Paresthesias (tingling, (numbness, burning) Emotional disturbances (depression, mood swings) § § § § Cognitive difficulties (memory, attention, processing) Pain (neurogenic) Heat sensitivity Spasticity Gait, balance, and coordination problems Speech/swallowing problems Tremor

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 (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 the different patterns (courses) of MS? • • Clinically Isolated Syndrome (CIS) Relapsing-Remitting MS (RRMS) Secondary Progressive MS (SPMS) Primary Progressive MS (PPMS)

What happens in MS over time? Secondary Progressive Disability Relapsing-remitting Time Disability Time § Relapsing course can be: -active or inactive -worsening or not worsening § Progressive courses can be: -active with or w/o progression -not active with or without progression Lublin, et al. Neurology 2013

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? • Thirteen disease-modifying therapies are FDA-approved for relapsing forms of MS: § glatiramer acetate (Copaxone®; Glatopa™ - generic equivalent) [inj. ] § interferon beta-1 a (Avonex®, Plegridy™, Rebif®) [inj. ] § interferon beta-1 b (Betaseron® and Extavia®) [inj. ] § dimethyl fumarate (Tecfidera®) [oral] § fingolimod (Gilenya®) [oral] § teriflunomide (Aubagio®) [oral] § alemtuzumab (Lemtrada®) [inf] § mitoxantrone [inf] § natalizumab (Tysabri®) [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 Pw. MS 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) • 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 • Depression is one of the most common symptoms of MS (resulting from immune system changes, neurologic changes and psychosocial factors) • >50% of people with MS will experience a major depressive episode. • Suicide in MS is 7 x 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, Ph. D § 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. Optimal Health with Multiple Sclerosis. New York: Demos Health, 2014

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. Optimal Health With Multiple Sclerosis. New York: Demos Health, 2014

Dietary Supplements to be Avoided Supplements that may stimulate the immune system: • • Alfalfa Ashwagandha Astragalus Cat’s claw Garlic Licorice Melatonin • Oligomeric proanthocyanidins • Pycnogenol • Saw palmetto • Selenium • Stinging nettle • Vitamin A • Zinc Bowling AC. Complementary and Alternative Medicine in Multiple Sclerosis (2 nd 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 • • • Nationwide network of 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 • Professional Resource Center Website: www. national. MSsociety. org/PRC 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