10) Multiple Sclerosis Flashcards
What is the class for IFN-beta-1a (Avonex)
IFN-beta-1a
What is the mechanism for IFN-beta-1a (Avonex)
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
What are the therapeutics for IFN-beta-1a (Avonex)
RRMS
What are the important side effects for IFN-beta-1a (Avonex)
Mild anemia, increase LFT (monitor every 6 mo.), hypothyroid; least NAB formed
What are the other side effects for IFN-beta-1a (Avonex)
Flu-like, minor irritation at inject site, anemia
What are the miscellaneous for IFN-beta-1a (Avonex)
Doesn’t cross BBB; decreases relapse rate by 1/3 and reduces MRI lesions, with a trend toward decreasing disability and brain atrophy
What is the class for IFN-beta-1a (Rebif)
IFN-beta
What is the mechanism for IFN-beta-1a (Rebif)
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
What are the therapeutics for IFN-beta-1a (Rebif)
RRMS (high-dose); first-line treatment (more efficacious than Avonex in head-to-head trials)
What are the important side effects for IFN-beta-1a (Rebif)
Anemia, leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.)
What are the other side effects for IFN-beta-1a (Rebif)
Flu-like, injection site reaction; neutropenia; thrombocytopenia
What are the miscellaneous for IFN-beta-1a (Rebif)
As with Avonex; significantly reduces new and enhancing MRI lesions, reduces disablity
What is the class for IFN-beta-1b (Betaseron)
IFN-beta
What is the mechanism for IFN-beta-1b (Betaseron)
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
What are the therapeutics for IFN-beta-1b (Betaseron)
RRMS (high-dose); more efficacious than Avonex in head-to-head trials
What are the important side effects for IFN-beta-1b (Betaseron)
Leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.); more NAB formed than avonex
What are the other side effects for IFN-beta-1b (Betaseron)
Flu-like, inject site reaction, anemia
What are the miscellaneous for IFN-beta-1b (Betaseron)
As with Avonex, but no effect on disease progression
What is the class for IFN-beta-1b (Extavia)
IFN-beta
What is the mechanism for IFN-beta-1b (Extavia)
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
What are the therapeutics for IFN-beta-1b (Extavia)
RRMS (high-dose)
What are the important side effects for IFN-beta-1b (Extavia)
Leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.)
What are the other side effects for IFN-beta-1b (Extavia)
Flu-like, inject site reaction, anemia
What are the miscellaneous for IFN-beta-1b (Extavia)
As with Avonex, but no effect on disease progression
What is the class for Glatiramer acetate (Copaxone)
Myelin basic protein analog
What is the mechanism for Glatiramer acetate (Copaxone)
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
What are the therapeutics for Glatiramer acetate (Copaxone)
RRMS
What are the important side effects for Glatiramer acetate (Copaxone)
Mild: injection site reaction, anxiety attack-like reaction
What are the miscellaneous for Glatiramer acetate (Copaxone)
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
What is the class for Natalizumab (Tysabri)
Monoclonal antibody
What is the mechanism for Natalizumab (Tysabri)
Binds VLA4 (integrin subunit), inhibiting leukocyte migration across BBB
What are the therapeutics for Natalizumab (Tysabri)
RRMS (2nd line)
What are the important side effects for Natalizumab (Tysabri)
PML (JC virus); acute urticaria, systemic hypersensitivity infusion reaction
What are the other side effects for Natalizumab (Tysabri)
Headache, dizziness, fatigue, arthralgia, rigors
What are the miscellaneous for Natalizumab (Tysabri)
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
What is the class for Fingolimod (Gilenya)
Sphingosine-1-phosphate analog
What is the mechanism for Fingolimod (Gilenya)
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)
What are the therapeutics for Fingolimod (Gilenya)
RRMS
What are the important side effects for Fingolimod (Gilenya)
Bradycardia and heartblock (EKG for first 6 hours); macular edema (need opthalmology exam before and after 3 months)
What are the other side effects for Fingolimod (Gilenya)
Reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, headache dizziness, infections
What are the miscellaneous for Fingolimod (Gilenya)
Patients must be VZV immune before prescription; oral daily
What is the class for Teriflunomide (Aubagio)
Immunosuppressants
What is the mechanism for Teriflunomide (Aubagio)
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)
What are the therapeutics for Teriflunomide (Aubagio)
RRMS
What are the important side effects for Teriflunomide (Aubagio)
Hepatotoxicity; teratogenicity (animal data)
What are the miscellaneous for Teriflunomide (Aubagio)
Oral daily
What is the mechanism for Dimethyl fumarate (Tecfidera)
Enhances Nrf2 pathway; some Th1 -> Th2 sgift
What are the important side effects for Dimethyl fumarate (Tecfidera)
N & V; diarrhea; stomach pain; flushing
What are the other side effects for Dimethyl fumarate (Tecfidera)
Itching, redness, rash
What are the miscellaneous for Dimethyl fumarate (Tecfidera)
Oral BID
What is the class for Mitoxantrone (Novantrone)
Anthracenedione
What is the mechanism for Mitoxantrone (Novantrone)
Broad immune suppression and modulation of B cells, T cells and macrophages; decreases frequency of clinical relapse, reduces disease progress, and reduces disability
What are the therapeutics for Mitoxantrone (Novantrone)
SPMS; RRMS (2nd line)
What are the important side effects for Mitoxantrone (Novantrone)
Dose-dependent cardiac toxicity (decreased LVEF, irreversible CHF); induction of acute leukemia
What are the other side effects for Mitoxantrone (Novantrone)
Nausea and vomiting, alopecia, menstrual irregularities, increased susceptibility to infection
What are the miscellaneous for Mitoxantrone (Novantrone)
IV; once/3 months
What is the class for Azathioprine (Imuran)
Immunosuppressants
What is the mechanism for Azathioprine (Imuran)
Immunosuppressive
What are the therapeutics for Azathioprine (Imuran)
SPMS (resistant, or as combination with other therapies)
What are the important side effects for Azathioprine (Imuran)
Systemic toxicity: monitor blood for changes
What is the class for Methotrexate (Trexall)
Immunosuppressants
What is the mechanism for Methotrexate (Trexall)
Immunosuppressive
What are the therapeutics for Methotrexate (Trexall)
SPMS (resistant, or as combination with other therapies)
What are the important side effects for Methotrexate (Trexall)
Systemic toxicity: monitor blood for changes
What is the class for Cyclophosphamide (Cytoxan)
Immunosuppressants
What is the mechanism for Cyclophosphamide (Cytoxan)
Immunosuppressive
What are the therapeutics for Cyclophosphamide (Cytoxan)
SPMS (resistant, or as combination with other therapies)
What are the important side effects for Cyclophosphamide (Cytoxan)
Systemic toxicity: monitor blood for changes
What is the class for Mycophenolate mofetil (CellCept)
Immunosuppressants
What is the mechanism for Mycophenolate mofetil (CellCept)
Immunosuppressive
What are the therapeutics for Mycophenolate mofetil (CellCept)
SPMS (resistant, or as combination with other therapies)
What are the important side effects for Mycophenolate mofetil (CellCept)
Systemic toxicity: monitor blood for changes
What are the miscellaneous for Mycophenolate mofetil (CellCept)
Oral
What is the class for Methylprednisone (MTP)
Corticosteroid (immunosuppressant)
What is the mechanism for Methylprednisone (MTP)
Unclear mechanism (suppress both B and T cells, may reduce cytokine release)
What are the therapeutics for Methylprednisone (MTP)
Acute MS attack, SPMS; shortens acute attack duration,speeds recovery
What are the other side effects for Methylprednisone (MTP)
Short-term: insomnia, mood changes, fluid retention, epigastric pain, hypertension; long-term: osteoporosis, cushingoid, secondary malignancies
What are the miscellaneous for Methylprednisone (MTP)
Given IV with oral prednisone taper
What are the therapeutics for ACTH
Acute MS attack (if patient allergic to corticosteroids, poor IV access); or if MTP doesn’t work
What is the mechanism for Plasmapharesis
Unclear mechanism
What are the therapeutics for Plasmapharesis
Acute MS attack not responsive to MTP