What T helper cell is pro-inflammatory?
Th1 and 17
What T helper cell is anti-inflammatory?
Th2
Define MS
immunologic disorder marked by chronic inflammation of the CNS
What is the key to the diagnosis of MS?
Dissemination of plaques in time and space
What are the three broad treatment categories for MS?
- Treatment of exacerbations-corticosteroids (anti-inflammatories)
- Disease-modifying therapies
- Symptomatic therapies for spasticity, bladder sx’s, sensory sx’s and fatigue
How are first line disease-modifying therapies (DMTs) administered?
Self-injected
Effects of DMTs
- Decrease annual relapse rate
2. Decrease formation of new white matter lesion
List the DMT agents
- Interferon (IFN) formulations
2. Glatiramer acetate (non-IFN)
List the 1st generation agents used for relapsing MS
- Interferon-B1a (Avonex, Rebif)
2. Interferon-B1b
List the 1st generation agents that are a Pregnancy Category C
- Interferon-B1b
2. Pegylated Interferon-B1a
List the 1st generation agents used for RRMS
- Pegylated Interferon-B1a
2. Glatiramer acetate
List the 1st generation agent that is administered as an IV infusion
Mitoxantrone
Mitoxantrone indications
- SPMS
- PRMS
- Worsening RRMS
List the 1st generation agent that are a Pregnancy Category B
Glatiramer acetate
List the 1st generation agents that are a Pregnancy Category D
Mitoxantrone
Interferon-B1a ADEs
- Depression
2. Flu like sx’s
Interferon-B1b ADEs
Depression
Glatiramer acetate ADEs
- Chest tightness
2. Urticaria- @ any dose!
Mitoxantrone ADEs
- Cardiotoxicity
2. AML
Natalizumab SEs
PML
Natalizumab monitoring
JVC antibody
Fingolimod ADEs
- Macular retinal edema
2. AV block
Teriflunomide ADEs
- Steven-Johnson Syndrome
- Liver failure
- TB activation
- Neutropenia
- Alopecia
Dimethyl fumarate ADEs
- Flushing-Take with food
- Rash/Pruritis
- Increased LFTs
- Albumineria
- GI discomfort
Alemtuzumab ADEs
Herpes Viral Infection
- Administer herpes viral prophylaxis starting on 1st day of Tx
- Continue for 2 months after completion of treatment OR
- until CD4 count @ 200
List the disease modifying ORAL agents indicated for relapsing forms of MS
- Natalizumab
- Fingolimod
- Teriflunomide
- Dimethyl fumarate
Alemtuzumab indications
RRMS
Ocrelizumab indications
Relapsing or Progressive MS
Define CIS
Clinically Isolated Syndrome
Frist episode of neurologic sx’s that lasts @ least 24 hrs
what do we use to treat exacerbation sx’s?
Corticosteroids
When should you initiate high dose corticosteroids (Methypredniolone, IV) with onset of sx’s? When do you start toe ee improvement of sx’s?
Within 2 weeks of sx onset
Improvement in 3-5 days
Longer durations of IV methylprednisolone ADEs
- Acne
- Fungal infection
- Mood alteration
Short term ADEs of methylprednisolone
- Metallic taste
2. Sleep disturbances
Which medication carries a pregnancy category X rating?
Teriflunomide
What labs would we monitor for adverse effects in Teriflunomide
- Pregnancy test
- LFTs
- CBC
- BP
- TB tst
IFN Beta 1a MOA
Alters expression and response to surface antigens enchanting immune cell activities
IFN Beta 1b MOA
- Balances the expression of pro and anti-inflammatory agents in the brain
- Reduces number of inflammatory cells that cross the BBB
Glatiramer acetate MOA
- Mimics the antigenic properties of Myelin Basic Protein (MBP)
- Inhibits binding of MBP t oTe-cell receptors
- Reduces inflammation, demyelination, and axonal damage
- Neuroprotective effect
Which medication has an indication for CIS and RRMS?
Glatiramer acetate
Three of the interferons are considered to be high potency medications. Which medication is consider a low potency medication?
Interferon beta 1a- brande name Avonex
If our patient was a female, which agent is a Category B Pregnancy?
Glatiramer acetate
Our patient reports a PMH of depression. Which medications would be considered a possible contraindication?
Interferons beta 1a and beta 1b
What is appropriate monitoring parameters for the interferon medications?
- Electrolytes
- CBC
- LFTs
- Thyroid function
- LVEF
- Depression
List the drugs that are used in cases of inadequate response or intolerance to first-line agents
- Fingolimod
- Natalizumab
- Alemtuzumab
- Mitoxantrone
what is the life time list of dose for mitoxantrone?
140 mg/m
Mitoxantrone ADEs
- Cardiotoxicity
- AML (acute myeloid leukemia)
- Pregnancy D
When is fingolimod contraindicated?
Patients receiving:
Class I and III antiarrythmic drugs
When is Mitoxantrone indicated?
- SPMS
- PRMS
- Worsening RRMS
What medication increases Fingolimod serum concentration? Why?
Ketoconazole
3A4 inhibition