Article

Let's Talk About Multiple Sclerosis

March is MS awareness month, spotlighting this chronic, progressive disease that is growing in prevalence.

Although there are more than 2 million people living with multiple sclerosis (MS), it is relatively uncommon to hear about these patients.1 But those who suffer from MS and their caregivers are aware of this debilitating autoimmune disease each day. They cope with the struggles that, for some, will only worsen over time. MS is a chronic and progressive disease that is growing in prevalence, without an apparent reason. It is estimated that about 200 people in the United States are diagnosed with MS each week.2 March is MS awareness month.

Epidemology

MS is most commonly diagnosed between age 20 and 50, with the first symptoms occurring between 30 and 35. MS occurs about twice as frequently in women as in men.3 A unique characteristic of MS is the global geographic trend. In general, the prevalence of MS is highest in areas further from the equator. Caucasians and people of Northern European descent are at greatest risk of developing MS compared with other ethnicities.3

Pathophysiology

MS is an autoimmune disease that destroys the myelin sheath surrounding the axon of nerve cells. Demyelination contributes to a wide variety of adverse effects associated with MS, such as fatigue, gait abnormalities, neuropathy, and visual disturbances.4 Without a specific diagnostic test for MS, it is often difficult to diagnose. Having health care professionals familiar with this disease is critical to early detection and slowing the disease progression.1 The most common way to evaluate MS is by obtaining a magnetic resonance imaging of the brain. This detects the hallmark lesions associated with MS but is often not done until a patient first has symptoms associated with the disease, known as a clinically isolated syndrome. These lesions most commonly occur in the brain, spinal cord, and optic nerves.

Clinical Presentation

There are 4 disease courses of MS (Table 1).2 MS is classified according to disease progression and the frequency of relapses and remission.5 The most common form of MS is relapsing-remitting (RRMS), which usually progresses into secondary-progressive (SPMS) over time.2 The clinical presentation of each disease course is noted in Table 1. Some courses of MS are more debilitating than others. However, what they all share is the lack of a cure. The course of MS varies widely, with many patients leading relatively normal lives with minimal symptoms to some who suffer severe disability. If a diagnosis of MS is made after age 50, the disease progression is usually more rapid, with worse outcomes.6 Initial symptoms often include fatigue, optic neuritis, or paresthesias.7,8 There are a multitude of symptoms that accompany MS as the disease progresses, and how they present can depend on the location of the lesions. For example, spinal cord involvement commonly causes motor and sensory changes, and brainstem involvement can present as some of the hallmark symptoms, such as ataxia and diplopia. Cerebral lesions are the most common but typically cause minimal symptoms. Some nonspecific symptoms associated with MS include bladder and bowel dysfunction, depression, and fatigue.9 MS is not fatal, and most people with the disease die of unrelated causes. However, there are complications from the disease that can be associated with a decreased life expectancy, such as suicide.10 The average life expectancy of those living with MS has increased considerably over the years but is still considered to be about 7 years shorter compared with those who do not have MS.11 Although the average life expectancy associated with MS is not dramatically lowered, the quality of life can be. It is important that caregivers, patients, and providers understand the importance of lifestyle changes and medication adherence to help slow disease progression.

Table 1. MS Disease Courses and Frequency 1,12,13

RRMS

85% are diagnosed with this course

Clearly defined periods of relapse followed by partial or complete remission where there is not apparent disease progression

SPMS

50% of those diagnosed with RRMS transition to this course within a decade

A steady, progressive phase that patients with RRMS usually enter over time

Primary-progressive (PPMS)

10% are diagnosed with this course

Steady disease progression, with no periods of relapse or remission

Progressive-relapsing (PRMS)

5% are diagnosed with this course

A mixture of steady progression and relapses

Treatment

It is important that patients with MS initiate disease-modifying therapy without delay to slow disease progression. Many of the disease-modifying agents approved for MS come with significant risks. Patients are often on multiple medications (Table 2) to control the symptoms associated with MS. Because of the nature of MS and the medications used to treat it, the clinician’s involvement is crucial for patients to have optimal disease outcomes. Involvement should improve adherence and quality of life by assisting with symptom control (Table 3). Studies have shown that disease-modifying medication adherence is associated with a lower risk of MS-associated hospitalizations and relapses.14 Non-pharmacological therapy can also be effective in improving quality of life, such as balance exercises, smoking cessation, and yoga.15,16 The University of Colorado School of Medicine developed a new program that focuses on sensory and visual stimulation with balance exercises versus traditional strength-building exercises, called Balance and Eye-Movement Exercises for People with Multiple Sclerosis. Patients who participated in the program were evaluated after 16 weeks of therapy and showed an overall improvement in balance, dizziness, and fatigue.16 Most MS patients will experience periods of relapses and require a 3-to-7-day course of intravenous methylprednisolone, with or without an oral prednisone taper. This is the treatment of choice to help decrease the inflammation and pain that patients experience.17 Several studies, including the Oral Versus Intravenous High-Dose Methylprednisolone for Treatment of Relapses in Patients with Multiple Sclerosis trial, have compared the efficacy of intravenous to oral corticosteroids in treating MS relapses, with comparable results.18,19,20

Table 2. MS Disease-Modifying Medications 5,21

Parenteral

Interferon beta-1a (Avonex, Rebif)

First-line option, notable for causing flu-like symptoms

Interferon beta-1b (Betaseron, Extavia)

First-line option, notable for causing flu-like symptoms

Glatiramer acetate (Copaxone, Glatopa)

First-line option, notable for post-injection reaction involving chest pain and flushing

Natalizumab (Tysabri)

Reserved for poor responders to first-line therapy; black box warning for progressive multifocal leukoencephalopathy

Mitoxantrone (Novantrone)

Reserved for poor responders to first-line therapy; black box warning for bone marrow suppression and cardiotoxicity

Oral

Dimethyl fumarate (Tecfidera)

Typically, more convenient but with increased risks; aspirin is recommended 30 minutes prior to administration to reduce flushing

Teriflunomide (Aubagio)

Typically, more convenient but with increased risks; teratogenic and requires wash-out period of up to 2 years (accelerated wash-out option with activated charcoal or cholestyramine)

Fingolimod (Gilenya)

Reserved for poor responders to first-line therapy; requires first-dose observation; contraindicated in many heart conditions

Table 3. MS Symptom Management22

Symptom

Treatment Options

Bladder dysfunction

Alpha blockers, anticholinergics, botulinum toxin, and desmopressin

Bowel dysfunction

Bulk-forming laxatives, increased fiber uptake, osmotic laxatives, and stimulant laxatives

Cognitive impairment

Improvement and support of coping strategies

Depression

Bupropion, serotonin norepinephrine reuptake inhibitors, and selective serotonin reuptake inhibitors (SSRI)

Fatigue

Amantadine, central nervous system stimulants, and SSRI

Gait impairment

Dalfampridine (Ampyra), physical therapy

Paroxysmal pain syndromes

Baclofen, carbamazepine, gabapentin, lamotrigine, misoprostol, and pregablin

Pseudobulbar affect

Dextromethorphan/Quinidine (Nuedexta)

Sexual dysfunction

Phosphodiesterase-5 inhibitors

Spasticity

Baclofen and tizanidine

Vertigo

Vestibular rehabilitation

Resources

MS can be overwhelming as a disease state, both emotionally and financially. There are several resources available to help patients and caregivers living with MS. The National Multiple Sclerosis Society provides information regarding MS fundraising events, research studies, support groups, and much more. Another useful resource for caregivers and patients is The Above MS program. This database has everything from exercises, recipes, and travel and work tips to services and webinars related to MS. Speak with a support coordinator by calling toll-free at 1-800-456-2255.23 Also, many local supports groups are available within the patients’ community.

Conclusion

This article is a brief highlight of this complex and potentially devastating disease. The numbers recorded for this disease only account for the patient and not the families that battle this disease as well. The true effect on families and patients increases as MS progresses, as some patients ultimately progress to disability. Although not fatal, MS, the sequelae or complications of the disease state can lead to premature death. The clinician can be involved in drug therapy and symptom management to improve the patient’s quality of life. This disease requires the coordinated assistance of an interdisciplinary team. In addition to drug and symptom management, an effective team is needed to facilitate coping strategies, disability assistance, and Social Security filings. With the abundance of emerging research and new medication options available to treat MS, there is hope for a future where those living with MS can enjoy fully functional and long lives.

This article was co-authored by Glenn Schulman, PharmD, MS, BCPS, BCACP, BCGP, a clinical hospital pharmacist in Pensacola, Florida, and Madison Como, a PharmD candidate at Florida Agricultural and Mechanical University in Tallahassee.

References

1. National Multiple Sclerosis Society. nationalmssociety.org/. Accessed February 14, 2018.

2. Tullman MJ. Overview of the epidemiology, diagnosis, and disease progression with multiple sclerosis. Am J Manag Care. 2013;19(2 Suppl):S15-S20.

3. MS Statistics. MultipleSclerosis.net. multiplesclerosis.net/what-is-ms/statistics/. Accessed February 18, 2018.

4. Demyelination: What is it and why does it happen? Healthline. healthline.com/health/multiple-sclerosis/demyelination. Accessed February 18, 2018.

5. Multiple Sclerosis. MultipleSclerosis.com. multiplesclerosis.com/us/treatment.php. Accessed February 16, 2018.

6. Polliack ML, Barak Y, Achiron A. Late-onset multiple sclerosis. J Am Geriatr Soc. 2001;49(2):168-71.

7. Olek MJ. Diagnosis of multiple sclerosis in adults. UpToDate. Accessed February 16, 2018.

8. Davis CP. Early multiple sclerosis (MS) signs and symptoms. MedicineNet.com. medicinenet.com/ms_multiple_sclerosis_symptoms_and_treatments/article.htm#at_what_age_does_ms_start. Accessed February 16, 2018.

9. Hersh CM, Fox RJ. Multiple Sclerosis. Cleveland Clinic. clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/multiple_sclerosis/. Published June 2014. Accessed February 18, 2018.

10. Davidson J. 7 things you don’t know about multiple sclerosis. Prevention. prevention.com/health/7-things-you-dont-know-about-multiple-sclerosis. Published February 23, 2016. Accessed February 16, 2018.

11. Marrie RA, Elliott L, Marriott J, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurology. 2015;85(3):240—7. doi: 10.1212/WNL.0000000000001718.

12. DiPiro JL, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill Education; 2016.

13. Pietrangelo A, Higuera V. Multiple sclerosis by the numbers: facts, statistics, and you. Healthline. healthline.com/health/multiple-sclerosis/facts-statistics-infographic. Accessed February 16, 2018.

14. Tan H, Cai Q, Agarwal S, Stephenson JJ, Kamat S. Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis. Adv Ther. 2011;28(1):51-61. doi: 10.1007/s12325-010-0093-7.

15. Stroup T. Multiple sclerosis and smoking. National Multiple Sclerosis Society. nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Research/Stroup_T_Smoking_and_MS_20151110.pdf. Accessed February 18, 2018.

16. Melao A. Balance, sensory stimulation exercises can improve MS symptoms, BEEMS program shows. Multiple Sclerosis News Today. multiplesclerosisnewstoday.com/2018/02/06/ms-symptoms-improved-beems-balance-sensory-stimulation-exercises-university-colorado-study-shows/. Published February 6, 2018. Accessed February 16, 2018.

17. Olek MJ, Howard J. Treatment of acute exacerbations of multiple sclerosis in adults. UptoDate. Accessed February 18, 2018.

18. Le Page E, Veillard D, Laplaud DA, et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2015;386(9997):974-81. doi: 10.1016/S0140-6736(15)61137-0.

19. Barnes D, Hughes RA, Morris RW, et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet. 1997;349(9056):902-6.

20. Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM. The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. Neurology. 2004;63(6):1079-80.

21. Aubagio [prescribing information]. Cambridge, MA: Genzyme, Corp; 2016. products.sanofi.us/aubagio/aubagio.pdf. Accessed February 18, 2018.

22. Olek MJ, Narayan RN, Frohman EM, Frohman TC. Symptom management of multiple sclerosis in adults. UptoDate. uptodate.com/contents/symptom-management-of-multiple-sclerosis-in-adults#H1126331. Accessed February 16, 2018.

23. Above MS. abovems.com/. Accessed February 18, 2018.

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