Multiple Sclerosis: Pharmacologic Choices
Multiple Sclerosis: Pharmacologic Choices
Multiple sclerosis (MS) is a chronic neurologic disorder characterized by targeted destruction of central
nervous system (CNS) myelin, as well as axonal degeneration and loss
There are currently no nonpharmacologic treatment strategies that affect the disease course of RRMS
Pharmacologic Choices
Although there is no known cure for MS, several disease-modifying therapies have been shown to
reduce the rate of relapses in RRMS, which may ultimately reduce/delay disease progression. Diseasemodifying
1-Glatiramer
Glatiramer acetate is an immunomodulator with effects similar to interferon beta on reduction in relapse rates and
MRI-detectable lesion burden in RRMS.
By inhibition of myelin reactive T cells, decreased T cell proliferation and decreased interferon-γ secretion.
Glatiramer has also demonstrated neuroprotective effects linked to increased brain-derived neurotrophic factor
(BDNF) expression, though the exact mechanism remains unclear.
Glatiramer reduces relapse rates in patients with RRMS but fails to prevent disease progression. Glatiramer has no
effect on primary or secondary progressive MS.
Glatiramer is well tolerated with few side effects, most notably a rare, acute, transient, postinjection reaction with
flushing, chest tightness, palpitations and dyspnea.
2-Interferons
It reduces the frequency of relapses and the size/number of lesions detectable on MRI and reduces the rate of
conversion to clinically definite MS following an initial clinically isolated
Whether interferon therapy delays onset of the progressive phase of the disease or slows progression of disability in
patients with secondary progressive MS is uncertain.
The most common side effects associated with interferon treatment include local injection site reactions and flu-like
symptoms.
The development of neutralizing antibodies can diminish the clinical response to interferon therapy.
Alemtuzumab is a monoclonal antibody that binds to CD52 on activated lymphocytes and targets
their destruction, leading to a reduction in relapse rates and sustained accumulation of disability in
patients with RRMS. Alemtuzumab was associated with a 50% greater reduction in relapse rates
compared with interferon beta.
Adverse effects include infusion reactions, infection and emergent autoimmunity, mainly affecting the thyroid gland.
Cases of progressive multifocal leukoencephalopathy (PML) occured
3-Dimethyl Fumarate
It activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is involved in the cellular response to
oxidative stress.
An exploratory comparison showed no significant differences between dimethyl fumarate and glatiramer.
Common side effects include flushing, nausea, vomiting, diarrhea, and abdominal pain. Decreased lymphocytes,
proteinuria and increased liver enzymes can also occur.
4-Fingolimod
Precautions include increased risk of macular edema, bradycardia, varicella-zoster infection, skin cancer and
reversible hepatic dysfunction. Liver enzymes should be measured at baseline and periodically throughout treatment.
Isolated cases of progressive multifocal leukoencephalopathy (PML) have been reported it may be increased in
patients who test positive for anti-JC virus antibodies.
5-Mitoxantrone
Mitoxantrone can reduce both the frequency of attacks and rate of disease progression.
Side effects including cardiotoxicity and leukemia require thoughtful assessment
of risk-benefit ratio.
Mitoxantrone therapy is usually reserved who have failed other therapy options.
6-Natalizumab
Natalizumab is an α4 integrin antagonist/adhesion molecule inhibitor, indicated for the treatment of RRMS.
Natalizumab blocks the attachment of T cells to the blood brain barrier, which precedes their infiltration into the CNS in
the early inflammatory stages of MS.
Teriflunomide reduces T- and B-cell activity through inhibition of dihydroorotate dehydrogenase-mediated pyrimidine
synthesis.
Adjunctive Therapies
8-Fampridine
Fampridine (4-aminopyridine) is approved in Canada to improve walking ability in patients with MS. As a selective
blocker of a subset of voltage-activated potassium channels with little or no effect on sodium or calcium channels
**All MS patients able to tolerate vitamin D should commence therapy with a supplement (at least 1000 IU per day),
especially if their levels are low