Disease-modifying Therapies

Question 1

Goals of therapy with DMT’s include…

Answer 1

Attempt to slow inflammatory process
Decrease frequency + severity of relapses
Decrease lesions on MRI
Reduce accumulation of neurological impairment + disability over time

Question 2

These DMT’s are injectables…

Answer 2

Interferon beta-1a + 1b
Peginterferon beta-1a
Glatiramer acetate
Ofatumumab

Question 3

These DMT’s are oral…

Answer 3

Dimethyl fumurate
Teriflunomide
Cladribine
Fingolimod, Siponimod, Ozanimod, Ponesimod

Question 4

These DMT’s are infused…

Answer 4

Natalizumab
Alemtuzumab
Ocrelizumab
Rituximab

Question 5

MOA of interferons + glatiramer is ____. They are different than other DMT’s because…

Answer 5

Immunomodulating/immounostimulator. Weaker than the other immunosuppressants which knock out specific parts of the immune pathway

Question 6

Progressive multifocal leukoencephalopathy (PML) is an…

Answer 6

Opportunistic infection caused by JC virus

Question 7

PML causes…

Pathophys + sx’s?

Answer 7

Destruction of cells that produce myelin - clumsiness, weakness, changes to vision + speech

Question 8

If a patient develops PML, we should…

Answer 8

“Fix” reason for immune suppression - stop medication, plasma exchange if needed

Question 9

These immunosuppressants have increased risk of causing PML…

Answer 9

Natalizumab
Dimethyl fumurate
Fingolimod
Ocrelizumab

Question 10

Interferon beta-1b is given…

Answer 10

SC every other day

Question 11

Interferon beta-1a is given…

Answer 11

IM once weekly
SC 3x weekly

Question 12

Peginterferon beta-1a is given…

Answer 12

SC every 2 weeks

Less frequent

Question 13

Common AE’s with the interferon therapies include…

Answer 13

Injection site rxn’s
Flu-like symptoms

Hepatotoxicity
Lymphopenia

Question 14

Glatiramer is given…

Answer 14

SC OD or 3x weekly

Question 15

Ofatumumab is given…

Answer 15

SC titration - once weekly, then every 4 weeks

Question 16

Common AE’s with glatiramer include…

Answer 16

Injection site reactions
Post injection systemic reactions
Lipoatrophy

Question 17

Common AE’s with ofatumumab include…

Answer 17

Injection site reactions

URTI, headache
Potential for serious infections - PML occurred with high doses

Question 18

Teriflunomide is given…

Answer 18

PO once daily

Question 19

Dimethyl fumurate is given…

Answer 19

PO BID

Question 20

Common AE’s with teriflunomide include…

Answer 20

Diarrhea/nausea, headache
Peripheral neuropathy
Hair thining

Hepatotoxicity

Question 21

All oral DMT’s are ____ and require

Answer 21

Potentially teratogenic - males and females

Need adequate birth control

Question 22

Common AE’s with dimethyl fumurate include…

Answer 22

GI intolerance
Flushing

Lymphopenia
Rare PML

Question 23

Fingolimod, siponimod, ozanimod, and ponesimod are given…

Answer 23

PO once daily

Question 24

Fingolimod is unique in that its AE’s…

Answer 24

Are significant for CV AE’s - QT prolongation, bradycardia, AV condution slowing; HTN

Macular edema
Herpes virus infections
Hepatoxicity

Rare PML

Question 25

Siponimod AE's compared to fingolimod is...

Answer 25

Less severe for CV AE's ## Footnote Ozanimod and ponesimod have less AE's in general

Question 26

Cladribine dosing is unique in that...

Answer 26

It is weight based AND once daily for 4/5 consecutive days beginning of each of the first 2 months of years 1 + 2 of treatment

Question 27

Notable AE's with cladribine include...

Answer 27

Flu-like symptoms (nausea, headache) Increased infection risk Potential teratogen in both males + females

Question 28

Natalizumab is given...

Answer 28

IV every 4 weeks

Question 29

Ocrelizumab is given...

Answer 29

IV at week 0 + week 2, then IV every 24 weeks

Question 30

Notable AE's with natalizumab include...

Answer 30

Increased infection risk Hepatotoxicity Hypersensitivity rxn's **PML especially if 2+ years**

Question 31

Notable AE's with ocrelizumab include...

Answer 31

Infusion reactions (pre-medicate with IV corticosteroid + antihistamine) Increased risk of infection, reactivation of HepB PML potential Potential teratogen

Question 32

Alemtuzumab is given...

Answer 32

1st course - IV once daily for 5 days 2nd course - IV once daily for 3 days, 12 months after course 1 Additional rounds IV once daily for 3 days, 1 year later.

Question 33

Notable AE's with alemtuzumab include...

Answer 33

**Infusion reactions** Development of autoimmune thyroid disorders, blood dyscrasias Increased risk of infection + malignancy

Question 34

If a patient experiences PML, we could try...

Answer 34

Rituximab (off-label for MS)