MS therapy Flashcards
Methylprednisone
Class: Corticosteroid (anti-inflammatory)
Mech: Unclear mechanism (suppress both B and T cells, may reduce cytokine release)
Thera: Acute MS attack, SPMS; shortens acute attack duration, speeds recovery
Tox: Short-term: insomnia, mood changes, fluid retention, epigastric pain, hypertension; long-term: osteoporosis, cushingoid, secondary malignancies
Misc: Given IV with oral prednisone taper
ACTH
Thera: Acute MS attack if patient is allergic to corticosteroids or poor IV access or if MTP does not work
Plasmapharesis
Mech: Unclear
Thera: Acute MS attack not responsive to MTP
IFN-beta-1a (Avonex)
Class: IFN-beta-1a
Mech: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
Thera: RRMS
Tox: Mild anemia, increase LFT (monitor every 6 mo.), hypothyroid; least NAB formed
Flu-like, minor irritation at inject site, anemia
Misc: Doesn’t cross BBB; decreases relapse rate by 1/3 and reduces MRI lesions, with a trend toward decreasing disability and brain atrophy
IFN-beta-1a (Rebif)
Class: IFN-beta
Mech: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
Thera: RRMS (high-dose); first-line treatment (more efficacious than Avonex in head-to-head trials)
Tox: Anemia, leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.)
Flu-like, injection site reaction; neutropenia; thrombocytopenia
Misc: As with Avonex; significantly reduces new and enhancing MRI lesions, reduces disablity
IFN-beta-1b (Betaseron)
Class: IFN-beta
Mech: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
Thera: RRMS (high-dose); more efficacious than Avonex in head-to-head trials
Tox: Leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.); more NAB formed than avonex
Flu-like, inject site reaction, anemia
Misc: As with Avonex, but no effect on disease progression
IFN-beta-1b (Extavia)
Class: IFN-beta
Mech: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
Thera: RRMS (high-dose)
Tox: Leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.)
Flu-like, inject site reaction, anemia
Misc: As with Avonex, but no effect on disease progression
Glatiramer acetate (Copaxone)
Class: Myelin basic protein analog
Mech: Mixture of 4 AAs in myelin basic protein; causes T-cell apoptosis (looks like MBP), induces anti-inflammatory Th2 cells (cytokine shift from Th1), induces Treg with induction of anergy
Thera: RRMS
Tox: Mild: injection site reaction, anxiety attack-like reaction
Misc: Active in CNS (not peripherally); try to use early; reduce relapse by 1/3, modest reduction in MRI lesion and reduction of atrophy, but no effect on disease progression
Natalizumab (Tysabri)
Class: Monoclonal antibody
Mech: Binds VLA4 (integrin subunit), inhibiting leukocyte migration across BBB
Thera: RRMS (2nd line)
Tox: PML (JC virus); acute urticaria, systemic hypersensitivity infusion reaction
Headache, dizziness, fatigue, arthralgia, rigors
Misc: Decrease relapse rate by 2/3, greatly reduce MRI lesions; once/month; antibodies to natalizumab cause it to stop working; side effects more common in patients positive for neutralizing antibodies
Fingolimod (Gilenya)
Class: Sphingosine-1-phosphate analog
Mech: Prodrug; sequesters circulating lymphocytes in secondary lymphoid organs via induction of intracellular internalization of receptors on lymphocytes (no effect on lymphocyte induction, proliferation, or memory function)
Thera: RRMS
Tox: Bradycardia and heartblock (EKG for first 6 hours); macular edema (need opthalmology exam before and after 3 months)
Reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, headache dizziness, infections
Misc: Patients must be VZV immune before prescription; oral daily
Teriflunomide (Aubagio)
Class: Immunosuppressants
Mech: Selective dihydro-orotate dehydrogenase inhibitor; blocks de novo pyramidine synthesis, reducing T- and B-cell proliferation and function against autoantigens; preserves replication and function of cells living on salvage pathway (e.g., hematopoietic cells, memory cells)
Thera: RRMS
Tox: Hepatotoxicity; teratogenicity (animal data)
Misc: Oral daily
Dimethyl fumarate (Tecfidera)
Mech: Enhances Nrf2 pathway; some Th1 -> Th2 shift
Tox: N & V; diarrhea; stomach pain; flushing
Itching, redness, rash
Misc: Oral BID
