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 The leading web portal for pharmacy resources, news, education and careers October 21, 2018
Pharmacy Choice - Multiple Sclerosis Disease State Management - October 21, 2018

Multiple Sclerosis Disease State Management

Multiple Sclerosis

Darrell Hulisz, RPh, PharmD
Associate Professor
Case Western Reserve University, School of Medicine
Clinical Pharmacy Specialist
University Hospitals Medical Group

Katlyn Pritchard
Pharmacy Intern
Ohio Northern University, College of Pharmacy

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS) that results in damage to the myelin sheath and nerve fibers. Complications include gait abnormalities due to muscle rigidity or spasms, tremor, urinary and bowel incontinence, erectile dysfunction, and impaired speech, vision and sensory input. In severe cases paralysis may occur. The most common symptoms include fatigue, loss of vision, depression, spasticity and motor weakness. Diagnosis is based on clinical symptoms (McDonald's criteria) and characteristic brain lesions shown by magnetic resonance imaging (MRI).1 MS is most commonly diagnosed between the ages of 20-50 with incidence peaking at 30 years old. There is also a higher incidence in females, Caucasians and in geographical locations such as the United States, Canada, Europe and New Zealand.2

The pathophysiology of MS is thought to involve processes of both the innate and adaptive immune system. Regulation of T cells is disrupted and cytokines disrupt the blood brain barrier allowing T cells to enter the CNS where multiple inflammatory cells such as macrophages and CD8+ lymphocytes contribute to nerve damage. Proposed factors that may increase the risk of MS development include gene variations (HLA-DRB1*15:01) and environmental factors such as Epstein-Barr virus infection, smoking, and vitamin D deficiency.3,4

There are four stages of MS based on severity of clinical symptoms and episodes of acute worsening. Clinically isolated syndrome (CIS) is the first episode of neurologic symptoms and may, or may not, progress further to a diagnosis of MS. Relapsing-remitting MS (RRMS) consist of episodes of acute worsening of neurologic function followed by remissions with no further progression. Approximately 85% of MS patients are diagnosed initially with RRMS. Secondary-progressive MS (SPMS) is steadily progressive with or without occasional relapses. Approximately 50% of those with RRMS will develop SPMS within 10 years of diagnosis. Primary-progressive MS (PPMS) is a nearly continuous worsening with or without relapses and the progression rate may vary over time.5,6

Treatment of MS is directed at reducing severity and frequency of relapses by the use of immune-modulating drug therapy; however, there is no cure for MS at this time. There are 15 drugs used for disease modifying therapy, most of which are only indicated for RRMS. Duration of therapy should generally not exceed two years due to potentially dangerous side effects with long-term use of immunosuppressive medications. Maintenance therapy is based around symptom management for complications such as incontinence, depression and spasticity.5-7

Oral medications indicated for RRMS include Fingolimod (Gilenya), teriflunomide (Aubagio) and dimethyl fumarate (Tecfidera). Interferon beta-1a (Rebif), peginterferon beta-1a (Plegridy), interferon beta-1b (Betaseron), daclizumab (Zinbryta) and glatiramer acetate (Copaxone) are subcutaneous injections indicated for RRMS, while interferon beta-1a (Avonex) is administered intramuscularly. Natalizumab (Tysabri) and alemtuzumab (Lemtrada) are intravenous infusions for RRMS.

Mitoxantrone is an antineoplastic agent administered intravenously and is indicated for SPMS or worsening RRMS however is not indicated in the treatment of patients with PPMS. Mitoxantrone has a black-box warning for cardiotoxicity, and secondary leukemia. Methotrexate has shown some benefit in delaying progression of upper limb impairment in SPMS. Ocrelizumab (Ocrevus) is a monoclonal antibody and the first drug to be approved for PPMS in March 2017 based on results from the ORATORIO trial. Ocrelizumab is administered intravenously and is contraindicated in active hepatitis B infection.6-8

Selection of the appropriate agent is based upon MS progression and severity as well as patient preferences and provider experience. Pharmacologic symptom management may include amantadine for fatigue, selective serotonin reuptake inhibitors (SSRIs) for depression, baclofen for spasticity, anticholinergics for urinary incontinence and bisacodyl rectal suppositories for neurogenic bowel. Dalfampridine (Ampyra) is the only FDA approved medication for impaired ambulation in MS. Supportive therapy such as occupational therapy, psychotherapy and speech pathology play an important role in symptom management.6,7

Non-pharmacologic measures for management include scheduled voiding and abdominal massage for bladder and bowel dysfunction. Light therapy may be considered for fatigue and tele-rehabilitation may have some benefit in cognitive function. Magnetic stimulation and other electromagnetic therapies may be used for spasticity, however evidence is inconclusive. Monitoring progression of symptoms is recommended every 3 months using the Expanded Disability Status Scale as well as a MRI every 12 months to monitor lesion formation.7,9

In summary, current treatment strategies for MS include a combination of supportive care, medications, treatment of associated co-morbidities, and behavioral strategies with a goal of symptom management and delay of disease progression. There is currently no cure for MS, however as research continues more treatments are likely to come on the market and recommendations for treatment may change.
  1. Kamińska J, Koper O, Piechal K, et al. Multiple sclerosis - etiology and diagnostic potential. Postepy Hig Med Dosw. 2017 Jun 30;71(0):551-563.
  2. Wingerchuck DM. Environmental factors in multiple sclerosis: Epstein-Barr virus, vitamin D, and cigarette smoking. Mt Sinai J Med. 2011 Mar-Apr;78(2):221-30.
  3. Leray E, Moreau T, Fromont A, et al. Epidemiology of multiple sclerosis. Rev Neurol. 2016 Jan;172(1):3-13.
  4. National Multiple Sclerosis Society. MS the Disease. Accessed October 30, 2017
  5. Tramacere I, DelGiovane C, Salanti G, et al. Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis. Cochrane Database Syst Rev. 2015.
  6. Multiple Sclerosis Coalition. The Use of Disease Modifying Therapies in Multiple Sclerosis Principles and Current Evidence. March 2017.
  7. Accessed October 30, 2017
  8. Luzzio C. Multiple Sclerosis Treatment & Management. October 2017. Accessed October 30, 2017.
  9. Lexicomp [Internet]. Hudson (OH): Wolters Kluwer. c1978-2016 [cited 2017 October 30].
  10. Amatya B, Khan F, La Mantia L, et al. Nonpharmacological interventions for treatment of spasticity in Multiple Sclerosis (MS). Cochrane Database Syst Rev. Feb 2013.

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