Multiple Sclerosis Drugs

Question 1

What 2-corticosteroid combination is commonly used to treat an acute MS attack? Give their routes of administration.

Answer 1

Methylprednisone given IV for 3-5 days, followed by predisone taper given orally

Question 2

What 2 treatments can be used to treat acute MS attacks in patients who are allergic or unresponsive to corticosteroids?

Answer 2

Plasmapharesis or ACTH

Question 3

Name the 4 immunomodulators that are currently 1st-line treatments for relapsing-remitting MS, giving both the molecules and brand names

Answer 3

IFNβ-1a: Αvonex and Rebif

IFNβ-1b: Betaseron and Extavia

Question 4

Which immunomodulator is currently first line treatment for relapsing-remitting MS? Does it work peripherally or centrally?

Answer 4

Rebif (IFNβ-1a), works peripherally (the INFs do not cross the BBB)

Question 5

All the immunomodulators can decrease relapse rate and MRI lesions for RRMS. Which class of immunomodulators can also reduce disease progression?

Answer 5

IFNβ-1a (IFNβ-1b have no effect on disease progression)

Question 6

Order the MS drugs from most efficacious to least efficacious, and from most to least neutralizing antibodies produced: Avonex, Rebif, Betaseron.

Answer 6

Efficacy: Rebif, Betaseron, Avonex (based on the fact that Rebif is 1st line for RRMS)
NAB: Betaseron, Rebif, Avonex

Question 7

What kind of molecule is glatiramer acetate (Copaxone), what is its main mechanism of action, and does it work peripherally or centrally?

Answer 7

An analog of myelin basic protein (MBP), mainly causes T-cell apoptosis, works centrally
(secondary mechanisms are to induce Th1 –> Th2 shift, and to induce Treg cells)

Question 8

Glatiramer acetate (Copaxone) can reduce relapse, MRI lesions, and brain atrophy in RRMS. Does it also reduce disease progression? What is its main side effect?

Answer 8

No effect on disease progression; side effect of panic attacks

Question 9

Name the monoclonal antibody that is 2nd or 3rd line treatment for RRMS. Does it reduce disease progression?

Answer 9

Natalizumab; does not reduce disease progression (does greatly reduce relapse rate and MRI lesions)

Question 10

Describe how natalizumab achieves its therapeutic effects.

Answer 10

Binds to VLA-4 subunit of leukocyte integrins, inhibiting leukocyte migration across the BBB

Question 11

What is the most significant long term side effect that may result from using natalizumab? What factors make patients at greater risk for getting this problem?

Answer 11

Patients may get PML (progressive multifocal leukoencephalopathy); associated with JC virus reactivation so anti-JC seropositivity and previous immunosuppression are risk factors

Question 12

How are the MS medications fingolimod, teriflunomide, and dimethyl fumarate (BG12) administered?

Answer 12

Orally (compared to the IFNβs, glatiramer acetate, and natalizumab, which are all injections)

Question 13

What MS drug has structural similarity to sphingosine-1-phosphate? How does it work?

Answer 13

Fingolimod; induces endocytosis of the S1P receptor, which causes sequestration of circulating lymphocytes in the lymphoid organs

Question 14

Give 3 significant side effects of fingolimod that require monitoring either before or during treatment (hint: not the reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, headache, dizziness, or infections…)

Answer 14

Bradycardia and heart block (requires EKG checks), macular edema (requires optho exams), and severe shingles (requires VZV immunity)

Question 15

How does teriflunomide achieve its immunosuppressant action, and what disease does it treat?

Answer 15

Inhibits DHODH (dihydro-orotate dehydrogenase) –> reduced pyrimidine synthesis –> reduced T- and B-cell proliferation; treats RRMS

Question 16

What are the 2 black box warnings for teriflunomide?

Answer 16

Hepatotoxicity and teratogenicity (so not recommended for pregnant women)

Question 17

What anti-inflammatory, neuroprotective drug, related to a class of psoriasis-treating drugs, is used to slow the disease progression of MS?

Answer 17

Dimethyl fumarate (BG12)

Question 18

Give the primary and secondary mechanisms of action of dimethyl fumarate (BG12).

Answer 18

Primary: enhance the Nrf2 pathway, which protects against oxidative stress
Secondary: induce a cytokine shift from Th1 to Th2

Question 19

What anthracenedione drug is the only FDA approved treatment for secondary progressive MS? Does it slow disease progression?

Answer 19

Mitoxantrone; slows disease progression

Question 20

How does mitoxantrone work, and what forms of MS is it used to treat?

Answer 20

Broadly immunosuppressive, modulates B-cells, T-cells, and macrophages; used to treat SPMS and RRMS (2nd line)

Question 21

Is mitoxantrone given orally or via IV? What is its most limiting side effect?

Answer 21

IV; causes cardiac toxicity (deceased LVEF, irreversible CHF)

Question 22

Mitoxantrone is associated with the induction of what kind of cancer?

Answer 22

Acute leukemia

Question 23

What kind of drugs are methotrexate and cyclophosphamide? What kind of MS are they used to treat, and (review from unit 1) what are their significant side effects?

Answer 23

Immunosuppressants; treat SPMS; side effects are pulmonary fibrosis and hepatotoxicity for methotrexate, and hemorrhagic cystitis for cyclophosphamide

Question 24

Azathioprine and mycophenolate mofetil are what kind of drugs, used to treat what kind of MS? Which one is given orally?

Answer 24

Immunosuppressants; for SPMS; mycophenolate mofetil is oral

Question 25

Which group of MS-treating drugs must be monitored for systemic toxicity?

Answer 25

The immunosuppressants (methotrexate, cyclophosphamide, azathioprine, and mycophenolate mofetil)

Question 26

What kinds of MS can pulse steroids be used to treat?

Answer 26

SPMS and PPMS (off label)