B3.024 Rheumatoid Arthritis Therapy Flashcards
DMARDs
disease modifying anti-rhuematic drug
immunosuppressive agents with goal of inducing/maintaining remission
older, oral
methotrexate mechanism
inhibition of dihydrofolate reductase-decreases synthesis of purines and pyrimidines thus interfering with DNA synthesis, repair, and cellular replication
increases adenosine release from cells which can dampen inflammation
what is given along with methotrexate
folic acid
prevent side effects
methotrexate administration
oral or subQ
weekly dose
low: 15-25 mg per week
methotrexate side effects
oral ulcers GI nausea cytopenias liver tox teratogen
leflunomide (Arava) mechanism
inhibits dihydroorotate dehydrogenase inhibiting pyrimidine synthesis leading to reduction of lymphocytes
leflunomide half life
prodrug; enterohepatocyte circulation leads to long half life
luflunomide administration
oral
leflunomide side effects
diarrhea
cytopenias
liver tox
teratogen
hydroxychloroquine mechanism
multiple
inhibits activity of TLRs
inhibits acidification of lysosomes ultimately interfering with antigen processing
hydroxychloroquine administration
oral
hydroxychloroquine side effects
rare retinal tox
sulfasalazine mechanism
sulfapyridine is active moiety but mechanism not identified
sulfasalazine administration
oral
sulfasalazine side effects
rash
GI
hepatotoxicity
cytopenias
azathioprine mechanism
protein synthesis inhibitor
azathioprine administration
oral
azathioprine side effects
cytopenias
rash
GI
pancreatitis
list all conventional DMARDs
methotrexate leflunomide hydroxychloroquine sulfasalazine azathioprine
what are biologics
newer medications that are made by molecular biologic techniques
what do biologics target
cytokines
T cell activation
deplete B cells
what is the main goal of TNF inhibitors
reduce joint inflammation and damage to joints
what are the different TNH inhibitors?
etanercept adalimumab certolizumab golimumuab infliximab
etanercept mechanism (subq)
fusion protein of TNF receptor linked to Fc portion of IgG
etanercept binds TNF and blocks its interaction with cell surface receptors
adalimumab &golimumab mechanism (subq)
human monoclonal antibodies directed against TNF
certolizumab mechanism (subq)
Fab fragment of a humanized monoclonal antibody directed against TNF
infliximab mechanism (infusion)
chimeric monoclonal antibody directed against TNF
tocilizumab mechanism
human monoclonal antibody targeting IL-6 receptor
reduces inflammation and joint damage
tocilizumab administration
subq or IV
ankinra mechanism
antagonist of IL-1 receptor
FDA approved for RA but not very effective
abatacept mechanism
binds CD80/86 on APCs, blocking the interaction of CD28 between APCs and T cells
results in T cells than cannot be activated fully
abatacept administration
subq or IV
rituximab mechanism
monoclonal antibody directed against CD20 antigen on B lymphocytes
result is depletion of B cells (but not existing plasma cells without CD20)
rituximab administration
IV
why is rituximab’s success surprising?
current understanding does not place B cells as most prominent player (T cells more prominent)
tofacitinib mechanism
inhibits JAK enzymes
prevents cytokine/growth factor mediated gene expression and intracellular activity of immune cells
what type of drug is tofacitinib?
targeting synthetic DMARD
one of the most effective
tofacitinib administration
oral
1st line approach to RA therapy
methotrexate
2nd line approach to RA therapy
either: sulfasalazide + hydroxychloroquine + methotrexate (triple therapy)
OR
TNF inhibitors + methotrexate
3rd line approach to RA therapy
abatacept rituximab tocilizumab anakinra tofacitinib
what are the combining factors that create “pre-arthritis”
susceptibility genes (MHC shared epitope, PAD, PTPN)
environmental factors
epigenetic modifications
post translational modifications (acetylation, carbanylation, citrullination…etc.)
what happens after pre-arthritis?
production of autoantibodies and loss of tolerance asymptomatic synovitis (cellular infiltrate) symptomatic arthritis
which RA drugs are teratogenic?
methotrexate leflunomide tocilizumab abatacept rituximab tofacitinib
