MS

Question 1

What are the two major theories as to who MS occurs?

Answer 1

1. Microbial: Virus directly attacks myelin or oligodendrocytes which in turn stimulates an immune response; Supportive evidence: increased IgG synthesis in CNS and Ab levels to certain viruses (HHV-6)
2. Autoimmune: Body recognizes myelin or oligodendrocytes as foreign and begins to attack; Inflammatory cascade is initiated

Question 2

What is the main type of drug used to treat acute exacerbations of MS?

Answer 2

Corticosteroids:

1. IV Solumedrol
2. Oral Prednisone
   - shorten duration of episode
   - does not alter progression of disease, no LT benefites

Question 3

Help to prevent relapse and progression; Initiate ASAP following diagnosis; Therapy should be continued indefinitely unless Clear lack of benefit, Intolerable side effects, or New clinical suggest otherwise

Answer 3

Disease modifying agents

Question 4

a common virus that is harmless in most people;Can cause a rare and serious brain infection (progressive multifocal leukoencephalopathy [PML]) in some patients who have weakened immune systems

Answer 4

John Cunningham (JC) virus

Question 5

Symptoms may include: progressive weakness on one side of the body, clumsiness, vision problems, confusion, and changes in thinking, personality, memory, and orientation; Can lead to severe disability or death.

Answer 5

PML

- damage to white matter

Question 6

What is the major downfall of disease modifying drugs for MS?

Answer 6

Very expensive; Monthly cost:

• Aubagio - $4,757.19
• Avonex - $5,058.19
• Betaseron - $5,809.69
• Copaxone - $6,000.09
• Extavia - $5,589.99
• Gilenya - $4790.19
• Rebif - $5,304.49
• Tecfidera - $5,320.09
• Tysabri - $5,629.49

Question 7

What are the different disease modifying agents for MS

Answer 7

1. Avonex and Rebif (Interferon β1-A)
2. Betaseron and Extavia (Interferon β1-B)
3. Copaxone (Glatiramer Acetate)

Question 8

Disease modifying agent MOA: Naturally occurring cytokines with immunomodulating activities that reduce the inflammatory process - Antiviral properties

Answer 8

Interferons

Question 9

Disease modifying agent MOA: Mimics the antigenic effects of myelin basic protein so that the binding of MBP peptides to T-cells is inhibited
Induced anti-inflammatory lymphocytes

Answer 9

Copaxone

Question 10

What are the ADRs of Betaseron?

Answer 10

1. Flu-like Sx (premedicate with Ibuprofen/APAP (Tylenol))
2. Pain, redness at injection site
3. SOB
4. Tachycardia
5. Leukopenia, Neutropenia, Increased LFT’s
6. Depression
7. Neutralizing antibodies
   - avonex and rebid have similar ADRs, but no incr in depression

Question 11

What does it mean when someone develops neutralizing antibodies to a disease modifying agent?

Answer 11

Neutralizes the drug after its injected – so getting same amt of drug but only certain amt is having effect

• typically appears btwn 6-15 mos into therapy
• Betaseron>Rebif>Avonex
• can’t switch to different interferon; antibodies have cross-over

Question 12

What are ADRs of Copaxone?

Answer 12

1. injection site pain
2. Neutralizing antibodies?
3. 10-15% of patients have chest tightness and flushing that resolves within 20 minutes

Question 13

What are ADRs of extavia?

Answer 13

1. Flu like symptoms – pretreat with analgesics or antipyretics on treatment days.
2. Liver injury (severe is rare)
3. allergic reactions
4. depression
5. CHD and cardiomyopathy
6. leukopenia
7. injection site necrosis, pain, rash
8. myalgia

Question 14

Alternative treatment for MS:
SAM blocker, white cells must bind adhesion molecules to cross arterial blood vessels and enter the brain; Originally withdrawn from the market due to leukoencephalopathy, also anaphylaxis and neutralizing Ab formation; Now back on the market, Dosed IV every 4 weeks

Answer 14

Tysabri (natalizumab)

Question 15

Alternative treatment for MS: Chemotherapy agent
For secondary progressive MS – slows progression; Dosed IV every 3 monthss; Cardiomyopathy – has maximal lifetime dose** (LVEF must be assessed prior to therapy; Left ventricular ejection fraction); May cause hair loss and leukopenia

Answer 15

Novatrone (mitoxantrone)

Question 16

Alternative treatment for MS: Boxed warning - Severe liver disease, Teratogenic; Adverse effects - hair loss, N&V, headache, paresthesias, HTN, arthralgias, and neutropenia ; Taken every day

Answer 16

Aubagio

Question 17

Alternative treatment for MS: Decreases incidence of relapse by 50%; MOA: sphingosine-1-phosphate receptor modulator, sequesters lymphocytes in lymph nodes, decreasing their role in immune responses (blocks, does not let cells get to where they need to be); ADRs: headache, head cold and fatigue, More serious side effects - a few cases of skin cancer, fatal infections, macular edema, PML
- Bradycardia: First dose monitoring (or after discontinuation of > 14 days); Pt’s need to be monitored for 6 hours after a dose
A: orally, daily
C/I: pt’s with hx of MI, unstable angina, stroke, TIA

Answer 17

Gilenya

Question 18

Alternative treatment for MS:
A: Oral, BID
ADR: flushing, abdominal pain, diarrhea, nausea, anaphylaxis, decreased lymphocytes
- One case of PML in a pt not on other medication - Pt had a low level of lymphocytes in her blood before therapy

Answer 18

Tecfidera

- decrease in lymphocytes = PML* - Damage to white matter because decrease in immune function