MS

Question 1

Tx of acute attacks

Answer 1

• corticosteroids (anti-inflammatory)
• plasmaphoresis
• ACTH

Question 2

mech of inteferons

Answer 2

• inhibit T cell activation
• cytokine shift from Th1 to Th2
• inhibit lympho migration into CNS
• antiproliferative effect
• apoptosis of autoreactive T cells
• antiviral effect
• dont cross BBB

Question 3

IFN beta-1a (Avonex)

Answer 3

• low-dose interferon (30 mcg IM/week)
• 1st line tx of RRMS
• less side effects (bc lower dose): flu-like symptoms, irritation at injection site, anemia, elevation of LFTs and hypothyroidism (need to do blood tests every 6 mos)
• least amount of NAb formed

Question 4

IFN beta-1a (Rebif)

Answer 4

• high dose IFN (44 mcg SQ)
• 1st line tx RRMS
• more SE: menstrual irregularities, depression, leukopenia,anemia, elevated LFTs, hypothyroidism (need to blood tests every 3 mo), flu-like sx, minor irriation-necrosis at injection site
• more efficacious than avonex

Question 5

IFN beta-1b (Betaseron and Extavia)

Answer 5

• high dose IFN
• 1st line tx: RRMS
• more SE: menstrual irregularities, depression, leukopenia/anemia, elevated LFTS, hypothyroidism (need to do blood tests every 3 mo), minor irritation - necrosis at injection site, flu-like sx
• more efficacious than avonex
• most NAbs

Question 6

Glatiramer Acetate (Copaxone)

Answer 6

• immunologically active analog of MBP (acts as a decoy); causes T-cell apoptosis, shift from Th1 to Th2, induces Treg, neuroprotection (?)
• 1st line tx RRMS –> use in PTs with (+) NAb titer
• mild SE: injection site reaction, self-limited anxiety like rxns (no blood tests needed!)
• as efficacious as high-dose IFNs and has less side effects, but you have to inject more frequently

COpaxone –> acts as deCOy

Question 7

Natalizumab (Tysabri)

Answer 7

• 2nd line tx for RRMS
• monoclonal Ab that binds alpha4 s/u of integrins expressed on leukocytes –> prevents their migration across BBB
• IV infusion
• risk of PML (predisposed to JCV infection)

Question 8

Fingolimod (Gilenya)

Answer 8

• tx RRMS (oral)
• progdrug with structural similarity to S1P —> lymphos have S1P receptors –> induces internalization of receptor and traps lympho in the LN
• SE: bradycardia, heart block, macular edema and less often: decreased FEV1, increased LFTs, leukopenia –> infections, asthenia, back pain
• must have VZV antibodies in order to administer (bc of risk of infection)
• **this drug has the most SE

Question 9

Teriflunomide

Answer 9

• tx of RRMS (oral)
• selective dihydro-orotate dehydrogenase inhibitor –> blocks pyrimidine synthesis –> reduce T and B cell proliferation
• relatively safe but 2 black box warnings: hepatotoxicity, teratogenicity
• efficacy = to 1st line injectables and easier to take (tablet form)

**teriflunOOOmide (Oral and dihydrO-Orotate dehydrogenase inhib)

Question 10

Dimethyl Fumarate (BG12)

Answer 10

• tx of RRMS (oral)
• neuroprotective effects: activates Nrf2 pathway which protects against oxidative stress
• significant effect on disease progression
• no black box warnings

Question 11

Mitoxantrone (Novantrone)

Answer 11

• only FDA approved tx for secondary-progressive MS (more severe- probably due to new inflamm activity)
• only tx that slows down disease progression
• immunosuppressive action
• SE: cardiac toxicity, N+V, alopecia, menstrual irregularities, increased susceptibility to infections, acute leukemia

**miTOXantrone (cardiac TOXicity)

Question 12

Azathioprine, MTX, cyclophosphamide, Mycophenolate mofetil

Answer 12

• Immunosuppresants
• tx resistant SPMS or as combo tx
• all have systemic toxicity and require blood monitoring

Question 13

Pulse steroids

Answer 13

• used for SPMS when these PTs have reached their max dose of Novantrone (140mg/m2) or have contraindications for its use

Question 14

Conclusions of 1st line tx

Answer 14

• rebif > avonex (Rebif more efficacious)
• rebif > betaseron (Rebif has less NAbs)
• rebif > copaxone (Rebif more efficiaous on MRI)
• all injectables
• more SE in IFNs = need to do blood tests routinely