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What is Multiple Sclerosis?

Multiple Sclerosis (MS) is an autoimmune disease that attacks the brain and spinal
cord, which make up the central nervous system. It specifically attacks the myelin
sheath that helps transmit signals from the brain to the rest of the body. This can cause a
wide range of symptoms that may vary from patient to patient and may be dependent on
how much nerve damage has occurred and which nerves were affected.
There are three types of MS: relapsing-remitting MS (RRMS), secondary-progressive
MS (SPMS), and primary-progressive MS (PPMS). At this time, it is not clear what
causes MS, and there is no cure.

Types of MS

According to the Multiple Sclerosis Association of America’s website,
there are three common variations of this disease. These variations are relapsing-
remitting MS (RRMS), secondary-progressive MS (SPMS), and progressive-
relapsing MS (PRMS). Some forms experience relapses or have remitting periods of no symptoms, while others have disabling symptoms that worsen over time. In addition
to these three main forms of the disease, there are other versions of the disease that
are not as common.

Risk Factors of MS

• ❖Age: can be present at any age, but commonly seen in those 20-40 years old
• ❖Sex: women’s chances are two to three times that of men for RRMS
• ❖Genetic Factors: major histocompatibility complex, if it runs in your immediate
  family
• ❖Environmental Factors: Vitamin D levels <40ng/mL (normally 40-60 ng/mL),
  UV radiation, Eptein-Barr virus infection, tobacco smoking,
  more temperate climates

What are common symptoms of MS?

• ❖Relating to movement : numbness or weakness in at least one limb on one side
  of the body, electric-shock experiences when bending your neck forward
  (Lhermitte sign), tremor, an unsteady gait (very common)
• ❖Relating to vision : loss in vision one eye before the other with eye pain,
  double vision, blurry vision
• ❖Relating to mood : anxiety, cognitive changes, depression
• ❖Other : slurred speech; fatigue; dizziness; tingling or pain in parts of your body;
  problems with sexual, bowel, and bladder function

See your healthcare provider if you develop these symptoms
(may not include all of the above because symptoms vary).

What first-line treatments are available for MS?

Although there is no cure, there are disease-modifying therapies (DMTs) available to
manage symptoms. Treatment can be broken down into long-term treatment for MS,
treatment of MS relapses, and MS symptom treatment.

Long-term treatment of MS, for relapsing and primary-progressive MS,
Ocrevus^TM (ocrelizumab) is the only approved DMT to treat this form of the disease
since 2017.
According to Lexicomp, the recommended dose is IV 300 mg on day 1, then 300 mg administered two weeks later, and then administering 600 mg once every six months
(six months from the first dose of 300 mg). If a dose is missed, take it as soon as
possible and change the dosing schedule to six months from the missed dose.
Contraindications are life-threatening reactions to this medication or active HBV
infection. The most common side effects include skin infections, upper respiratory
tract infections, a general infection, infusion related reactions, and/or decreased
immunoglobulins (IgM mostly) or decreased neutrophils.

For RRMS, first-line treatment is injectable medications, which includes interferon beta medications and glatiramer acetate (Copaxone, Glatopa). Lexicomp reports glatiramer
acetate dosing at 20 mg subcutaneously injected once daily or 40 mg administered subcutaneously three times per week and administered at least 48 hours apart.
Lexicomp also reports adverse effects of glatiramer acetate that include chest pain,
vasodilation, and skin rash among others, and a contraindication of hypersensitivity
to the medication.

An example of interferon beta medications would be Avonex®. According to
Lexicomp, target dosing can be either 22 or 44 mcg given subcutaneously three times
weekly with doses separated by at least 48 hours. To decrease flu-like symptoms, the
dose and frequency can be reduced weekly. Contraindications include hypersensitivity
to an interferon beta or other part of this formulation. Adverse reactions noted are
abdominal pain, nausea, urinary tract infection, injection site reaction, myalgia,
back pain, flu-like symptoms, fever, upper respiratory tract infection, among others.

Oral treatment includes Mayzent^® (siponimod) and Mavenclad^® (cladribine),
oral tablets for RRMS and active SPMS that were approved in 2019. 20 DMTs and
their generic forms are approved for RRMS and active SPMS. Vumerity^TM
 (diroximel fumarate) is in oral capsule form that treats RRMS, SPMS, and one of the
lesser known forms of the disease, clinically isolated syndrome (CIS).

Additionally, for MS relapses, IV methylprednisolone or dexamethasone
(as an alternative to methylprednisolone) is recommended by IV infusion.
According to Lexicomp, for IV methylprednisolone, 500 mg to 1 g is given daily for
three to seven days, followed by oral prednisone.¹ It is contraindicated in those with hypersensitivity to methylprednisolone and includes a wide range of side effects that
are not specified which is more common, so follow-up with PCP if experiencing strange
side effects. For dexamethasone, the dose is not indicated in our sources or Lexicomp
for MS, but it is contraindicated in those with a hypersensitivity to this medication.
As side effects, patients cna experience CNS effects, GI effects, hyperglycemia, and
adrenal suppression among others.

For those with severe MS, first-line treatment would be natalizumab (Tysabri),
which stops immune cells from attacking the spinal cord and brain. For those that have
positive antibodies of progressive multifocal leukoencephalopathy (PML) JC virus,
they have a higher risk with this medication to have PML than those without the
antibodies. According to Lexicomp, natalizumab is given by IV as 300 mg infused over
one hour every four weeks. The common side effects of this medication include a skin
rash, abdominal distress, nausea, depression, fatigue, headache, limb pain, or flu-like
symptoms, and make the patient more susceptible to a respiratory tract infection.

In addition to the treatments mentioned, there are numerous other treatments that
are considered based on other conditions of the patient to treat the specific symptoms
experienced by the patient, and treatment is individualized.

What role does a pharmacist have?

Pharmacists are available to counsel on the medications the patient is prescribed for
their condition. They counsel on what dose the patient is on, how to take the medication,
how long treatment is meant to last, and any side effects that may occur. They can also recommend over-the-counter medications to help with some of the symptoms or
counsel on reducing the risk factors such as smoking cessation. Examples of how a
pharmacist can assist in OTC recommendations, for bowel issues due to MS, a
pharmacist can recommend stool softeners, bulk forming agents, oral laxatives, suppositories/rectal stimulants, or for overall management, the use of
Metamucil® or Imodium®.³ Another example would be pharmacists suggesting meclizine (Antivert®)
or diphenhydramine (Benadryl®) among other OTC options to help with the
dizziness/vertigo often experienced by MS patients.

Other than OTC medications that can be recommended by a pharmacist and
counseled on accordingly, a pharmacist can take the prescription medications sent in for
MS and counsel the patient on those as well. An example would be dalfampridine
(Ampyra®), which is commonly prescribed for walking or mobility issues, and the
walking gait is usually a common sign of MS.

According to Lexicomp, dalfampridine’s dose is 10 mg given orally every twelve hours
(max dose of 20 mg/day). If the patient misses a dose, they are going to skip it and not
take an extra dose. Contraindications are if the patient has a sensitivity to this
medication, a history of seizures, or moderate to severe renal impairment. Common
side effects include a urinary tract infection, nausea, dizziness, headache, insomnia,
vomiting, and vertigo among others.

References:

1. Etanercept. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL
2. Mayo Foundation for Medical Education and Research. (2022, February 18).
   Multiple Sclerosis. Mayo Clinic. Retrieved February 18, 2022, from https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms
   -causes/syc-20350269
3. McGinley, M. P., Goldschmidt, C. H., & Rae-Grant, A. D. (2021). Diagnosis and
   Treatment of Multiple Sclerosis: A Review. JAMA, 325(8), 765–779. https://doi.org/10.1001/jama.2020.26858
4. Multiple Sclerosis Association of America – improving lives Today! MSAA.
   (2022, February 14). Retrieved February 20, 2022, from https://mymsaa.org/
5. National Multiple Sclerosis Society. (n.d.). Retrieved February 18, 2022, from https://www.nationalmssociety.org/

Author:

Shelby Johnson, PharmD Candidate 2024

University of Louisiana Monroe College of Pharmacy