Rheumatoid Arthritis Flashcards
Pharmacologic treatment
not able to cure pts or reverse the damage that’s been done
adjunct therapy: NSAIDs, corticosteroids
DMARDs, biologic agents anti-TNF, biologic agents (non-TNF)
NSAIDs
effective in reducing pain, swelling, and stiffness
do NOT alter disease progression
dose at anti-inflammatory doses
use in combo with DMARDs
ex. ibuprofen, naproxen, celecoxib (don’t use in pts with sulfa allergy!)
antinflammatory doses are higher
Corticosteroids
used for anti-inflammatory + immunosuppressive properties
not used as monotherapy
use in combo with DMARD
use in acute flares (to try and decrease the flare to save/preserve the DMARD)
use in pts with extra-articular manifestations
ex. prednisone
trying for lowest dose possible b/c of AEs, try to go for short term treatment
Corticosteroid AES
short term: hyperglycemia, gastritis, mood changes, elevated BP
long term: aseptic necrosis, cataracts, obesity, growth failure, osteoporosis
Monitoring parameters for corticosteroids
baseline: BP, BG
maintenance: BP q3-6mo, BG q3-6mo
Disease modifying anti-rheumatic drugs (DMARDs)
potential to decrease/prevent joint damage and preserve joint integrity
timing of initiation is critical
onset of action is delayed
DMARDs meds
methotrexate, sulfasalazine, hydroxychloroquine, leflunomide
Methotrexate
gold standard of treatment!
most predictable benefit
DMARD of choice and with best long-term outcome
Methotrexate MOA
inhibit dihydrofolic acid reductase (inhibits neutrophil adhesion and chemotaxis)
Methotrexate dosing
2.5mg tabs
dose: 7.5mg per WEEK by mouth or IM (up to 15-20 mg)
onset: 1-2 mo
MTX AEs
hematologic: bone marrow suppression
gastrointestinal: N/V/D, stomatitis, mucositis (taking with food helps) - folic acid supplementation 1mg/day to reduce sx
hepatic: cirrhosis, hepatitis, fibrosis
pulmonary: pneumonitis, fibrosis
dermatologic: rash, urticaria, alopecia
teratogenic: wait one cycle of BCP, wait 3 mo before considering conception
MTX contraindications
pregnancy, chronic liver disease (EtOH abuse), immunodeficiency, pre-existing blood dyscrasias, pleural/peritonal effusions, leukopenia/thrombocytopenia, CrCl< 40ml/min
MTX monitoring
baseline: CXR, CBC, SCr, LFTs, albumin
maintenance: CBC, SCr, LFT: <3mo: 2-4wks; 3-6mo: 8-12wks; >6mo: 12wks
Leflunomide MOA
prodrug
inhibit de novo biosynthesis of pyrimidines, interferes with tyrosine kinase activity, inhibits cell cycle progression
Leflunomide dosing
requires loading dose
teratogenic: use cholestyramine to clear from system b/c of it’s long t1/2 (16 days)
Leflunomide AEs
diarrhea, rash, alopecia, increased LFTs, teratogenicity
Leflunomide monitoring
CBC, SCr, LFT
baseline and maintenance: <3mo: 2-4wks; 3-6mo: 8-12wks, >6mo: 12wks
Sulfasalazine MOA
prodrug - cleaved in colon to sulfpyradine and 5-ASA
inhibits IL-1
do NOT use in pt with sulfa allergy!
Sulfasalazine AEs
gastrointestinal: N/V/D, anorexia
dermatologic: rash/urticaria/photosensitivity*
hematologic: leukopenia, thrombocytopenia; rare: hemolytic and aplastic anemia
caution for allergy
Sulfasalazine monitoring
CBC, SCr, LFT
baseline
maintenance: <3mo: 2-4wks; 3-6mo: 8-12wks; >6mo: 12wks
Hydroxychloroquine MOA
modification of cytokine infiltration in joint
used in earlier treatment (not as effective as others)
Hydroxychloroquine AEs
advantage: no myelosuppression, hepatic, renal toxicities*
ocular: retinal toxicity*; >70yo, cumulative dose >800g, night/peripheral changes
gastrointestinal: N/V/D (take w/ food)
dermatologic: increase skin pigment, rash, alopecia
Hydroxychloroquine monitoring
vision exam
baseline
every 6-12mo
“appealing” because really no monitoring
Biologic response modifiers (biologic DMARDs)
TNF neutralizers: etanercept, infliximab, adalimumab, golimumab, certolizumab
all impact + neutralize TNF in different ways, if fail one, can try another in same class
TNF neutralizers warnings/precautions
risk of infection
do not use in combo with IL-1 inhibitors or T-cell co-stimulation modulators (further increases risk of infection + AEs)
black box warnings, increased neurologic/demyelinating disorders, malignancies, congestive HF, hepatitis B reactivation, no concurrent live vaccine administration (TB testing to make sure no latent TB)
TNF neutralizers AEs
HAs and rash, risk of infection (upper respiratory most common), injection site rxn, exarcerbations of CHF, risk of malignancy, risk of evidence of demyelinating disease
Etanercept
binds to and inhibits TNF - binding occurs before the cytokine can interact with cell-surface TNF receptors that would produce an inflammatory response
SC!
Infliximab
binds and inhibits TNF
IV!
indicated in combo with MTX, could be used as monotherapy
Adalimumab
binds and inhibits TNF
for pts who have inadequate response to one or more DMARDs; can be used alone or in combo
SC every other week!
Golimumab
binds and inhibits TNF
for moderate to severe RA; used in combo with MTX
SC once monthly!
monitor: CBC with PLT and LFTs
Certolizumab
binds and inhibits TNF
for RA pts with moderate to severe disease; can be used alone or in combo with non-BRM DMARDs
SC!
Anakinra
IL-1 inhibitor
for moderate to severe RA in pts who have failed one or more DMARDs; can use alone or in combo
SC!
do not use in combo with TNF agents or abatacept
Anakinra AEs
injection site rxns, HA, N/V, flu-like sx, hypersensitivity to e.coli derived proteins, increased risk of serious infection, decreased neutrophils
Anakinra monitoring
neutrophil count
prior to start, monthly for 3 mo, quarterly for up to one year
Selective T-cell co-stimulation modulator
abatacept
Abatacept
for moderate to severe RA; if had inadequate response to one or more DMARDs
monotherapy or in combo with DMARD (not with TNF inhibitors or IL-1 antagonists)
inhibits T-cell activation
IV!
Abatacept warnings
do not use with TNF antagonists or IL-1 antagonists
increased risk of infection
no live vaccine administration
caution in pts with COPD*
Abatacept AEs
HA, nausea, upper respiratory infection, nasopharingitis, infusion rxns, serious infection, malignancy
IL-6 receptor inhibitors
tocilizumab (IV) and sarilumab (SC)
for moderate to severe RA after inadequate response to one or more DMARDs
alone or in combo with MTX or another DMARD
IL-6 receptor inhibitors MOA
binds to soluble and membrane bound IL-6 receptors
IL-6 inhibitor warnings
black box warning: serious infections*
contraindicated in pts with liver toxicity, thrombocytopenia, and neutropenia
IL-6 inhibitor AEs
serious infection, liver toxicity, thrombocytopenia, neutropenia, lipid abnormalities, intestinal perforations (tocilizumab), infusion rxns (tocilizumab)
IL-6 inhibitor monitoring parameters
neutrophil count - at 4-8wks then q3mo
platelet count - at 4-8wks then q3mo
LFTs - at 4-8wks then q3mo
lipid profile - after 4-8wks then q6mo
Anti-CD20 antibody
rituximab
“last resort” - reserved for pts who have failed others; for moderate to severe RA; in those with inadequate response to TNF antagonists; used in combo with MTX
bind specifically to antigen CD20
Rituximab dosing
IV
administer methylprednisolone 30 min before infusion to reduce infusion rxns
Rituximab AEs
tumor lysis syndrome, mucocutaneous rxns, viral infection, hypersensitivity, renal toxicity, bowel obstruction, hep B reactivation, cardiac arrhythmia
Rituximab monitoring
CBC with platelet, serum creatinine, vital signs (during infusions)
Targeted synthetic DMARDs
janus kinase inhibitors
Janus kinase inhibitors
these are oral agents!
for moderate to severe RA after inadequate response to TNF; used alone or in combo with MTX or another DMARD; NOT in combo with BRM, azathioprine, or cyclosporine
Janus kinase inhibitors MOA
inhibits janus kinase
JAK inhibitor meds
tofacitinib
baricitinib
upadacitinib
JAK inhibitors warnings
cytochrome P450 interactions; do not use in hepatic impairment; risk of infection; risk of malignancy; major adverse CV events; thrombosis; GI perforations; no live vaccines
do NOT use if: Hgb < 9mg/dL, ANC < 1000 cells/mm^3, ALC < 500 cells/mm^3
JAK inhibitors AEs and monitoring parameters
upper respiratory, HA, nausea
monitoring: lympocyte count, neutrophil count, Hgb, liver enzymes, lipid profile
Combination therapy
drugs with different MOA; allows for decreased dosages and minimizes AEs; more effective in treating resistance; may provide dramatic slowing of progression; MTX most common in combo with other DMARDs
Therapeutic decisions
treat to target approach
different considerations for stratification of patients: early RA vs established RA
