0% found this document useful (0 votes)
30 views3 pages

Multiple Sclerosis: Pharmacologic Choices

Multiple sclerosis is a chronic neurologic disorder characterized by destruction of myelin in the central nervous system and axonal damage. There are four main types: relapsing-remitting, primary progressive, secondary progressive, and progressive-relapsing. While there is no cure, several disease-modifying therapies have been shown to reduce relapses in relapsing-remitting MS, including glatiramer acetate, interferon beta, dimethyl fumarate, fingolimod, alemtuzumab, natalizumab, teriflunomide, and mitoxantrone. These drugs work by modulating the immune system to decrease inflammation in the brain. Adjunctive therapies like famp

Uploaded by

Bishoy Youssef
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as DOCX, PDF, TXT or read online on Scribd
0% found this document useful (0 votes)
30 views3 pages

Multiple Sclerosis: Pharmacologic Choices

Multiple sclerosis is a chronic neurologic disorder characterized by destruction of myelin in the central nervous system and axonal damage. There are four main types: relapsing-remitting, primary progressive, secondary progressive, and progressive-relapsing. While there is no cure, several disease-modifying therapies have been shown to reduce relapses in relapsing-remitting MS, including glatiramer acetate, interferon beta, dimethyl fumarate, fingolimod, alemtuzumab, natalizumab, teriflunomide, and mitoxantrone. These drugs work by modulating the immune system to decrease inflammation in the brain. Adjunctive therapies like famp

Uploaded by

Bishoy Youssef
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as DOCX, PDF, TXT or read online on Scribd
You are on page 1/ 3

Multiple Sclerosis

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

Four basic types of MS are identified:

i) Relapsing Remitting (RRMS)


ii) Primary Progressive (PPMS)
iii) Secondary Progressive (SPMS)
iv) Progressive Relapsing (PRMS)

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

Short courses of high-dose Corticosteroids, Methylprednisolone 1 g IV daily for 3–5 days

First-line Disease-modifying Therapies

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

Interferon beta is a standard first-line therapy option in the treatment of MS.

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.

Alternative Disease-modifying Therapies

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

Dimethyl fumarate is an oral agent for management of RRMS.

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

Fingolimod is a sphingosine-1-phosphate receptor agonist that blocks the egress of activated,


presumably autoimmune lymphocytes into the circulating bloodstream from lymphoid tissues.

It is 2nd line of TTT

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 is an anthracenedione antineoplastic agent that is sometimes used off-label for


secondary progressive MS, progressive relapsing MS and refractory cases of RRMS.

Mitoxantrone suppresses immune cell activity and is considered a potent immunomodulator.

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.

It reduce immune cell activation and promote apoptosis of lymphocytes.

Natalizumab is associated with hypersensitivity reactions and, notably, risk of PML


7-Teriflunomide

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

You might also like