Multiple Sclerosis

Question 1

Methylprednisone class, mxn, for, adinistered how, side effects?

Answer 1

Corticosteroid; Anti-inflammatory suppression of B & T cells, cytokine release; Acute MS attack – shorten the acute attack and hasten recovery; Given IV with oral prednisone taper; (short term) insomnia, mood changes, fluid retention, epigastric pain, HTN + (long term) osteoporosis, cushingoid, secondary malignancies.

Question 2

Besides methylprednisone, what else is useful for acute attacks? How is the latter given and why?

Answer 2

Plasmaphoresis. ACTH – given SC or IM, especially for those allergic to corticosteroids or with poor IV access.

Question 3

MOA of interferons for MS?

Answer 3

Inhibit T cell activation, Mediate TH1 to TH2 shift, inhibit lymphocyte movement to CNS, anti-proliferative, apoptosis of T cells, anti-viral, IFNy antagonism.

Question 4

IFN-betas used to treat MS?

Answer 4

Avonex & Rebif (IFNb1a) + Betaseron + Extavia (IFNb1b)

Question 5

Avonex is considered? For? Dosed? Effectiveness?

Answer 5

“low-dose IFN”; RRMS; 30 mcg IM/wk; Decreases relapse rate by 1/3, enhancing MRI lesions, atrophy & disability.

Question 6

Rebif is considered? For? Dosed? Efficacy?

Answer 6

“high-dose IFN”; 1st line for RRMS; 44mcg SQ 3X/wk; More efficacious than Avonex

Question 7

Betaseron and Extavia are considered? For? Dosed? Efficacy?

Answer 7

“high-dose IFN” 1st line for RRMS; 0.25 mcg SQ every other day; More efficacious than Avonex, but no effect on disease progression

Question 8

Rebif, Betaseron & Extavia side effects?

Answer 8

Flu-like, injection site reaction, menstrual irregularities, depression, leukopenia/anemia, increased LFTs, hypothyroidism (monitor every 3 months for 1st yr)

Question 9

Avonex side effects?

Answer 9

Less than others – flu-like, injection site, mild anemia, increased LFTs, hypothyroidism (monitor every 6 months)

Question 10

Have neutralizing Abs been detected with all IFN use? Which gives most NABs? Least?

Answer 10

Yes. Most: Betaseron & Extavia. Least: Avonex.

Question 11

PEG-IFNB1a dose? Efficacy? SEs?

Answer 11

SC 125 mcg every 2 wks; effective; SEs similar to Avonex w/ greater flu-like.

Question 12

Glatiramer acetate (Copaxone) class? Mxn? For? Dose? Efficacy? SEs?

Answer 12

Myelin Basic Protein analog; Causes T-cel apoptosis, induces anti-inflammatory TH2 (w/ shift from TH1), induces Tregs; RRMS; 20mg SC/day; Decreases relapse rate, MRI lesions, but NO effect on progression (basically as effective as Betaseron & Rebif); Mild SEs – anxiety attack-like rxn

Question 13

For 1st line, what are the conclusions?

Answer 13

Earlier tx is better; Higher and more frequent dosing is better; ROA may not matter. Drug choice ultimately based on POE, but: Rebif more efficacious than Avonex & Gatiramer acetate (Copaxone), Rebif causes less NABs than Betaseron/Extavia,

Question 14

Natalizumab class? Mxn? For? Dose? Efficacy? SEs?

Answer 14

Monoclonal AB; Binds VLA4 (integrin subunit) & inhibits leukocyte migration across BBB; considered 2nd line for RRMS; IV/month; very effective; SEs PML, systemic hypersensitivity infusion rxn, acute urticaria, HAs, dizziness, fatigue arthralgia, rigors (SEs especially in those with NABs)

Question 15

Fingolimod class? Mxn? For? Dose? Efficacy? SEs?

Answer 15

Sphingosine-1-analog; sequesters circulating lymphocytes in secondary lymphoid organs via induction of intracellular internalization of receptors on lymphocytes (w/o effects on induction, proliferation, memory); RRMS; oral prodrug 1X/day; effective; bradycardia, heartblock (monitor EKG for 1st 6 hrs), macular edema (need optho exam before and after 3 months), reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, HA, dizziness, infections – pts MUST be VZV immune before prescription.

Question 16

Teriflunomide class? Mxn? For? Dose? Efficacy? SEs?

Answer 16

Immunosuppresant; Selective DHOD inhibitor, blocking de novo pyramidine synthesis, redicung T and B proliferation and function, but preserving replication of salvage pathway; RRMS; oral daily; efficacy = to 1st line injetables; SE: hepatotoxicity, teratogenicity

Question 17

DImethyl fumarate class? Mxn? For? Dose? Efficacy? SEs?

Answer 17

Oral formulation of dimethylfumarate; Neuroprotective (activates Nrf2 pthway, clearing free radicals and protecting against oxidant stress) + Anti-inflammatory (TH1 –> TH2); MS; oral BID; effective; NO black box warning (SEs - N/V/D, itching/redness/rash)

Question 18

Mitoxantrone class? Mxn? For? Dose? Efficacy? SEs?

Answer 18

Anthracenedione; Broad immune suppresion and modulation of Bs, Ts, macrophages; 2nd line for RRMS & SPMS; IV 1X/3 months; Decreases relapses, progression, disability; SEs - dose-dep cardiotoxicity, acute leukemia, N/V, alopecia, menstrual irregularities, infection

Question 19

Immunosuppressants used for MS? Uses as? SEs?

Answer 19

Azathioprine, Methotrexate, Cyclophosphamide, Mycophenolate mofetil; Used for pts who have failed immunomodulators, or as an odd on); all cause systemic toxicity and require blood monitoring

Question 20

Is there an FDA approved drug for primary progressive MS (PPMS)?

Answer 20

No – use immunosuppressants, pulse steroids, IVIG