Pharmacist Rounds: Prompt Treatment Improves Outcomes for MS Patients

Dr. Zanni is a psychologist and health-systems consultant based in Alexandria, Virginia.

When we think of disabling neurologic disorders, we rarely think of young adults, but multiple sclerosis' (MS) lifetime risk of 1 in 400 makes it the most common among people aged 20 to 40 years, affecting twice as many women as men.^1-3 The severity of the disease varies, often marked by relapses, remissions, and disease progression. Although life expectancy for MS patients is normal, increased debilitation is common. Within 10 years of diagnosis, approximately 50% of patients use a cane, and at 25 years, 90% have substantial disabilities.^1,4

This idiopathic central nervous system (CNS) inflammatory autoimmune disease is characterized by demyelination of nerve fibers. Hardened (sclerosed) scar tissue forms over the demyelinated nerve fibers and delays or completely blocks nerve impulses, eventually resulting in axonal degeneration. Its etiology remains unknown, but researchers believe environmental,genetic, and viral infections are involved.¹

In MS, multiple neurologic deficits depend on the location and number of sclerotic sites. Presenting symptoms typically include unilateral numbness or weakness in 1 or more limbs or in the bottom half of the body, partial or complete vision loss, painful eye moments, balance problems and dizziness, bladder urgency, fatigue, and depression. Optic neuritis is an especially common presenting symptom. Although disease progression is heterogeneous, 4 subtypes are used to classify MS:

• Relapsing-remitting MS, affecting about 85% of patients, is characterized by acute flare-ups lasting weeks or months, followed by periods of remission.
• Secondary progressive MS is characterized by acute flare-ups and remission, but over time, patients transition into steady deterioration unrelated to acute attacks. Approximately 80% of those diagnosed with relapsing-remitting MS transition into secondary progressive MS.
• Primary progressive MS, representing 10% of cases, is marked by steady deterioration and no acute attacks, leading to the most severe disabilities.
• As the rarest subtype, progressive-relapsing MS is characterized by a progressive decline accompanied by occasional acute attacks.¹

Diagnosis requires the presence of 2 or more confirmed brain or spinal cord neurologic deficits that are disseminatedin time and space (ie, occurring in different parts of the CNS, separated by at least 3 months).² Multiple magnetic resonance imaging scans are generally used to confirm diagnostic accuracy. The diagnosis process must rule out comparable conditions like CNS infection (eg, Lyme disease, HIV) and other CNS inflammatory disorders (eg, sarcoidosis,lupus, Sj?gren's syndrome).

Treatment

In many instances, an initial acute MS attack leads to subsequent evaluation and diagnosis. Glucocorticosteroids are recommended. Research demonstrates they shorten relapse duration, but appear to have little effect on altering longterm disease progression.^1,2

Several clinical trials have studied the effectiveness of plasma exchange. Although data suggest little impact ondisease progression, it was helpful in treating severe, acute episodes in individuals unresponsive to glucocorticosteroidtherapy.^3,5

Acute attacks are often associated with triggers. Excessive heat, both in air and water (ie, hot saunas), is a commontrigger. Keeping a patient diary helps identify patient-specific triggers.

Disease-Modifying Strategies

Treatment should be initiated promptly to prevent further disability. Data suggest irreversible axonal damage may occur early in relapsing-remitting MS, and FDA-approved agents appear to minimize new lesions more effectively than they repair existing lesions.² No long-term studies on agents' safety and effectiveness exist; practitioners must assess risks and benefits, which is admittedly difficult, since clinical progression varies from person to person.

Four agents (Table 1) are approved for initial MS management: intramuscular interferon beta-1a, subcutaneous interferon beta-1a, interferon beta-1b, and glatiramer acetate. A fifth agent, mitoxantrone, is approved for secondary progressive MS and worsening forms of relapsing-remitting MS.² Currently no effective therapies exist for primary progressiveMS and progressive-relapsing MS.¹ Although not FDA-approved for MS, some physicians report that intravenousimmunoglobulins may create positive outcomes for patients with severe, rapidly progressive MS.¹

Table 1

In 2006, the FDA approved natalizumab, a monoclonal antibody, for patients who fail to respond to other agents. Themanufacturer had withdrawn natalizumab when 3 patients developed progressive multifocal leukoencephalopathy; it is currently only available through the manufacturer's risk management TOUCH Prescribing Program.⁶

Secondary Treatment and Rehabilitation

Physical and occupational therapy and pharmacotherapy target secondary symptoms. Some secondary symptoms appear initially, but for many MS patients, others emerge with disease progression. Common secondary symptoms include fatigue, bladder dysfunction, urinary tract infections (UTIs), bowel problems, spasticity, ataxia and tremor, visual and other sensory problems, neuropathic pain, cognitive losses, speech, and pressure sores. Table 2 highlights recommendations for symptoms frequently seen in chronic care settings.

Table 2

Experienced by 75% to 95% of patients, fatigue is a significant cause for unemployment.⁸ MS-related fatigue may be primary or secondary. Secondary symptom fatigue is frequently attributed to coexisting morbidities, medications,depression, or disrupted sleep. In the 2-step treatment process, clinicians must assess, treat, and/or minimize fatigue attributed to secondary causes. For example, up to 35% of MS patients report sleep disturbances. Because spasticity requires increased energy expenditure for daily activities, minimizing spasticity may minimize fatigue.⁸

The second step involves treating primary MS fatigue. Although the FDA has not approved drugs for MS fatigue, many practitioners prescribe amantadine, modafinil, or methylphenidate. Amantadine, for example, effectively reduces fatigue in 20% to 40% in mild-to-moderately disabled MS patients.⁸

Along with treatment, environmental modifications and the use of assisted devices also can help reduce fatigue associated with expending energy on routine daily activities. Canes and scooters, for example, conserve energy for those with ambulatory problems. Many patients are initially resistant to assisted devices, mistakenly believing they are "giving in." Counseling must emphasize that these devices often increase mobility, and subsequently, increase overall well-being.⁴

Like other age-related illnesses, the risk for UTIs, pneumonia, septicemia, and cellulitis increases in older MS patients, compared with younger patients.⁴ Additionally, up to 65% of patients experience MS-related cognitivedeficits that can be confused with other neurologic disorders. As with all chronic conditions, ongoing physicaland psychological assessments facilitate responsive treatment revisions.

REFERENCES

• Kieseier BC, Hartung HP. Current disease-modifying therapies in multiple sclerosis. Semin Neurol. 2003;23(2):133-146.
• Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004;70(10):1935-1944.
• Multiple Sclerosis. Mayo Clinic Web site. www.mayoclinic.com/health/multiple-sclerosis/DS00188. Accessed March 24, 2008.
• Dilorenzo T. Aging with multiple sclerosis. National Multiple Sclerosis Society Web site. www.nationalmssociety.org/for-professionals/~. Accessed March 27, 2008.
• Goodin D, Frohman E, Garmany G, et al. Disease Modifying Therapies in Multiple Sclerosis. Report of The Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. www.neurology.org/cgi/data/58/2/169/DC3/1. Accessed March 27, 2008.
• Natalizumab Information FDA Web site. www.fda.gov/cder/drug/infopage/natalizumab. Accessed March 31, 2008.
• National Guideline Clearinghouse. Multiple sclerosis. National clinical guideline for diagnosis and management in primary and secondary care. www.guideline.gov/summary/summary.aspx?doc_id=5063. Accessed March 27, 2008.
• National Multiple Sclerosis Society. Management of MS-related fatigue. (Expert Opinion Paper from the medical advisory board of the National Multiple Sclerosis Society). www.nationalmssociety.org/for-professionals/~. Accessed March 28, 2008.

ONLINE WEB EXCLUSIVE: Interactive Case Scenario

Eva was 35 years old when she experienced her first symptom: a tingling in one arm. She initially ignored it, until the tingling transitioned into partial numbness. Six months later, she was diagnosed with relapsing-remitting multiple sclerosis. Her neurologist indicates she is at risk for transitioning to progressive-relapsing multiple sclerosis.

1. Regarding disease-modifying therapy, which of the following is false?

• First-line agents are more effective in preventing new lesions than in repairing existing lesions.
• First-line agents may alter the risk of transitioning into progressive-relapsing multiple sclerosis.
• First-line agents should be initiated as soon as possible.
• Glucocorticosteroids therapy should be initiated concurrent with first-line agents.
• Long term safety for first-line agents has not been studied.

2. Two years following diagnosis, Eva reports chronic fatigue and does not know if she can continue working. What issues should practitioners examine?

• Determine if fatigue is the result of depression or sleep disturbances.
• Use a 2-step process, focusing first on secondary causes of fatigue.
• Review current medications for fatigue-inducing side effects.
• Assess if too much energy is expended on routine daily activities.
• All of the above.

ANSWERS

1: d

2: e

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