Lecture 40-41 - Pharmacotherapy of Multiple Sclerosis Flashcards
Dissemination in Time (DIT)
Time between evidence of new lesions in subsequent MRIs (30 days) – damage that has happened more than once
Dissemination in Space (DIS)
Need for > 1 T2 lesion appearing in at least two of four MS‐typical CNS regions (cortical, periventricular, infratentorial, spinal cord) – damage that is in more than one place
Diagnosis of MS requires
having at least 2 demyelination‐related episodes separated by time and space; new criteria allows for use of MRI and CSF testing at the first event for diagnosis
Clinically Isolated Syndrome (CIS):
descriptor of a first demyelinating event involving the optic nerve, cerebrum, cerebellum, brainstem or spinal cord
most will develop MS within 20 years
Relapsing Remitting MS (RRMS):
most common type (80 – 90% of diagnoses); consists of relapses with partial or complete remission between relapses; most will become progressive type over time
Secondary Progressive MS (SPMS):
~ 80% of RRMS patients will progress to SPMS, consisting of fewer relapses with continuing disability
Primary Progressive MS (PPMS):
10 – 15% of patients – progressive form from onset with minor
improvements or periods of stability; more common in patients diagnosed in later years (> 50 years of age)
Progressive Relapsing MS (PRMS):
least common form (~ 5% of diagnoses); steadily worsening disease from onset with later, clear, acute relapses; may be some recovery from acute attacks, but no remission between relapses
EDSS is used to
assess effectiveness of drug therapy
0: normal neurological function
1: no disability with only minimal signs
2: minimal disability
3: moderate disability
4: relatively severe disability
5: disability affects full daily activities (cane)
6: assistance required to walk and work (walker)
7: essentially restricted to a wheelchair
8: restricted to bed or wheelchair
9: bedridden inable to communicate effectively or eat/swallow
10: death
Treatment of acute attacks
High‐dose corticosteroid treatment is the first
choice; oral or intravenous treatment based on setting (inpatient vs. outpatient)
Methylprednisolone 500mg – 1000mg IV daily for 3 to 7 days, with or without an oral taper over 1 – 3 weeks
If outpatient: oral prednisone 1250mg every other day x 5 doses without need for taper
Oral medications
Dimethyl fumurate (Tecfidera®)
Diroximel fumarate (Vumerity®)
Fingolimod (Gilenya®, Tascenso ODT®)
Ozanimod (Zeposia®)
Ponesimod (Ponvory®)
Siponimod (Mayzent®)
Teriflunomide (Aubagio®)
Injectable medications
Interferon beta‐1a (Avonex®, Rebif®)
Peginterferon beta‐1a (Plegridy®)
Interferon beta‐1b (Betaseron®, Extavia®)
Glatiramer acetate (Copaxone®)
Infusion medications
Alemtuzumab (Lemtrada®)
Natalizumab (Tysabri®)
Ocrelizumab (Ocrevus®) - only one indicated for PPMS
Progressive multifocal leukoencephalopathy
Rare, serious adverse event caused by reactivation of dormant JCV; decreases functioning of person’s immune system
Causes the cells that produce myelin to break down, can look similar to a MS relapse
Patients must be tested for JCV antibodies (prior to getting med for MS)
Vaccines
Inactivated vaccines are preferred for people with multiple sclerosis
Live, attenuated vaccines are not recommended because the ability to cause the disease is weakened, but not eliminated
Alemtuzumab - no live virus vaccines
Varicella vaccine should be considered by people with MS who have never had chicken pox, especially if they may start a MS medication that suppresses cell‐ mediated immunity (fingolimod, alemtuzumab)
DIMETHYL FUMARATE, DIROXIMEL FUMARATE MONOMETHYL FUMARATE
Capsule SHOULD NOT be opened and sprinkled on food; do not chew or crush
Monitor LFTs (hepatotoxicity) and CBC with differential (neutropenia)
Associated with PML
Can cause flushing, may take aspirin 30 minutes prior to dose
SPHINGOSINE 1‐PHOSPHATE RECEPTOR MODULATORS
fingolimod, ozanimod, ponesimod, siponimod
CONTRAINDICATED with past arrhythmia diagnosis; or any of the following CV diagnoses in the past 6 months: MI, unstable angina, stroke/TIA, Class III/IV heart failure
Discontinuation can result in significant worsening of MS symptoms
must be monitored for 6 hours after 1st dose, may cause bradycardia
Ozanimod
avoid use with an MAO inhibitor
Siponimod
CYP2C9 genotype testing required before prescribing
GLATIRAMER ACETATE
Injection side effects: immediately post‐injection – flushing, sweating, dyspnea, chest pain, anxiety, itching (you must rotate injection sites)
Lipoatrophy may occur at injection site that is likely permanent – educate to rotate injection sites
Chest pain may occur outside of injection, usually not clinically significant
May be preferred if treatment is necessary in pregnancy – teratogenic effects are unknown
INTERFERONS
Can be dosed subcutaneously or IM every other day to every 2 weeks depending on the dosage form
Flu‐like symptoms can occur after injection – decrease risk by pre‐treating with acetaminophen or an NSAID, dosing in the evening/at bedtime and gradual dose titration
Psychiatric side effects: depression, suicidal thinking
Elevated liver function tests and thyroid dysfunction – monitor LFTs and TSH
MONOCLONAL ANTIBODIES
alemtuzumab
natalizumab
ocrelizumab
can premedicate with steroid, antihistamine, acetaminophen prior to dose
complete vaccinations at least 6 weeks before starting treatment
Alemtuzumab
- REMS program
- Possible fatal infusion
reactions and autoimmune
conditions - Associated with increased
risk of malignancies - Contraindicated in HIV
infection – prolonged ↓ CD4
count
Natalizumab
REMS program
significant association with PML
Ocrelizumab
- Only drug FDA‐approved for PPMS!!
- Contraindicated in active hepatitis B
- Associated with increased risk of malignancies
MS and pregnancy
rates of relapse of MS decreases during pregnancy increases for the first 3 mo post-partum then returns to pre-pregnancy rate
MS therapy should be discontinued prior to conception, not advised to breastfeed post-partum if restart MS treatment
Pregnancy - teriflunomide
contraindicated (accelerated elimination - cholestyramine or activated charcoal for 11 days)
Pregnancy - mitoxantrone
contraceptive required for treatment, pregnancy test before each infusion
Pregnancy - fingolimod
contraceptive during treatment and for at least 2 mo after D/C
Pregnancy - ozanimod
contraception during treatment and for at least 3 mo after D/C
Pregnancy - ponesimod
contraception during treatment and for at least 7 dyas after D/C
Pregnancy - siponimid
contraceptive during treatment and for at least 10 days afer D/C
Pregnancy - ocrelizumab
contraceptive during treatment and for at least 6 mo after D/C
Pregnancy - cladribine
contraceptive required + barrier method for at least 6 mo after D/C
contraindicated in breastfeeding
Gait abnormalities/walking speed
dalfampridine blocks potassium channels and prevents repolarization of the cell, which prolongs action potentials and nerve impulse transmission in the demyelinated axon, which may improve walking speed
IR dosage form and dose escalation associated with seizures; contraindicated in pts with h/o seizures
Symptomatic management
baclofen for the treatment of spasticity in MS
Medical marijuana in MS
spasticity: OCE/THC effective to decrease pt reported scores, not effective to decrease objective scores
central pain, painful spasma: OCE effective to decrease central pain, THC probably effective to decrease painful spasms
tremor, bladder dysfunction: OCE probably ineffective, THC probably ineffective
