RA Flashcards
RA targets the
synovium and sometimes other internal organs
what is the hallmark of RA
persistent symmetric synovial proliferation and tenderness of multiple joints- esp in the hands and feet
what is the prognosis of RA
poor, with progressive joint damage and deformity
Acute/ chronic pain
Erosions on X ray = deformities
Long term disabilities
Reduced life expectancy
what causes RA?
External trigger leads to autoimmune reactions in genetically susceptible individual with rheumatoid factor (RF) and/or anti citrullinated protein antibody (ACPA)
chronic inflammation in RA leads to
presence of pannus
influx of inflammatory cells in synovial fluid
angiogenesis
what is a pannus
thickened, inflamed joint lining
onset of RA is usually
insidious- over weeks or months
what is the distribution of RA
initially oligoarticular, progressing to polyarthritis, can affect almost any joint + symmetrical in presentation
most common in hands and feet
list 3 sx of RA
morning stiffness (gelling) for >1hr, symmetrical swelling and tenderness = reduced grip strength + inability to make fist, reduced function, systemic (fatigue, poor sleep, low energy, weight loss, low grade fever)
anemia, keratoconjunctivitis sicca, carpal tunnel sx/ tarsal tunnel sx, rheumatoid nodules and baker’s cysts
what are the 4 complications of RA
CVD, infections, cancer, osteoporosis
3 joints commonly affected by RA
PIP, MCP, MTP
is this inflammatory of noninflammatory arthritis? the pt has pain at rest and with activity, soft tissue swelling, and morning stiffness that lasts an hour
inflammamtory
is this inflammatory of noninflammatory arthritis? the pt has pain with activity and bony joint swelling, there is no local erythema or warmth
noninflam
which 2 lab findings point towards RA
rheumatoid factor
ACPA
CRP elevated
increased WBCs and platelets, decreased Hb
image findings on early RA
periarticular swelling, joint effusions
image findings on intermed RA
uniform joint space narrowing and marginal erosions
image findings in late RA
malalignment due to joint damage, periarticular osteopenia, and erosions
what are 3 measuring scales for RA
ACR20
DAS28
HAQ
describe the “window of opportunity” in RA
timeframe within which there is disproportionate response to therapy, resulting in LT sustained benefits
describe the “T2T” approach in RA
Early aggressive tx (regular reassessment, making changes individually) tailored to the disease activity of an individual pt aimed at achieving remission critical for optimizing LT results
why do guidelines start to use monotx or the T2T approach in RA?
1. because monotx is just as effective as combo
2. because methotrexate must first be trialed before being combined with another agent to determine pt tolerability
3. because monotx works better than combo tx
4. because monotx achieves remission in 1/3 -1/2 patients anyways and may be more cost effective
5. because there is no rush to control the disease early, as it takes weeks to months to progress
4
describe the step up tx approach in RA
initial monotx, add DMARDs q3-6mths prn (used in North America)
describe the combo approach in RA
initial combo tx, add/ switch DMARDs q3-6mths prn
describe the step down approach in RA
initial biologic DMARD and/or prednisone in combination, add/ switch DMARDs q3-6mths prn (usually not used due to expenses)
how often should RA tx be reassessed
q3mths
csDMARDs include
MTX, LF, SZZ, HCQ, chloroquine
tsDMARDs include
tofaciinib, baricitinib, upadacitinib
DMARDs should be introduced ___, ____ is the preferred agent with respect to efficacy and safety in initial tx of RA
ASAP
MTX
combination tx with csDMARDs should be considered in those with
Poor prognostic features
Mod-high disease activity
Recent onset disease
in combo tx, what is usually the anchor drug
MTX
DMARDs are the mainstay of RA tx because they
modify disease process, prevent/ reduce joint damage
DMARDs are
1. immune modulating
2. antiinflammatory
3. immunosuppressive
4. all of the above
1
csDMARDs should be initiated ___________, usually bridged with
soon after disease onset
bridge with short course of prednisone or NSAIDs
MTX dose in RA
15-25mg qwk
how to adjust MTX dose based on renal
Reduce dose by 50% if CrCL 10-50mL/min (some avoid if <30)
MTX onset and max eff
onset 2-4wks
max 3-6mths
MTX MOA in chemo
inhibits dihydrofolate reductase = inhibits purine synthesis
MTX MOA in RA
Stimulates release of adenosine = anti inflam + inhibits neutrophils
what indicates that MTX is working in RA
increased MCV by 5pg/fL
list 3 common SEs of MTX
mouth/ nose ulcers (3-10% tx w/ folic acid), N/V, loss of appetite (>10% tx w/ folic acid), fatigue, malaise 24-48hrs after dose (tx w/ dextromethorphan)
which 2 agents can be used to tx MTX SEs
folic acid and dextromethorphan
folic acid can prevent MTX SEs like
mouth/ nose ulcers, hair loss, ALT/ AST elevation
dextromethorphan prevents MTX SEs including
malaise, fatigue, headaches, memory impairment
how does dex prevent MTX SEs
blocks neurostimulation of homocysteine (↑ due to MTX ant of folic acid) at NMDA receptor in brain = avoids headache, lethargy, malaise, memory impairment/fogginess from homocysteine (10mL BID on day of + day after MTX)
how should you advise a patient that has forgotten to take a dose of MTX
1. take one dose ASAP, then take the next dose at the same time you usually do next week
2. take one dose ASAP, then if the usual time is <4 days away, push to next week, if >4 days = take on usual day
3. if <2 days to next dose, skip and take next dose
4. if <4 days to next dose, skip and double next dose
5. take one dose ASAP, then take next dose a 6-7 days after (can take 1 day early every week to get back to previous schedule)
6. take one dose ASAP, then take next dose 5-7 days after (can take 2 days early per week get back to previous schedule)
5
which of the following is not CI in pregnancy
1. MTX
2. SSZ
3. LF
4. HCQ
2, 4
which of the following should not be used with MTX
1. NSAIDs
2. penicillins
3. pantoprazole
4. trimethoprim
5. quinolones
4
LF onset and max eff
onset 6-8wks, max 3-6mths
LF common AEs
diarrhea, ↓ hair, ↑ liver enzyme, mouth/ nose ulcers, N/V, ↓ appetite, HA
interstitial lung disease is a rare SE of
1. LF
2. MTX
3. HCQ
4. CA
1
what is used for LF washout
cholestyramine
LF should be stopped ____ before conception
1. 1yr
2. 2 yrs
3. 2 yrs + washout
4. doesn’t have to be, is safe in preg
2
can you use alcohol on LF?
yes, 1-2/wk but caution if also on MTX
which does not require renal adjustment
1. MTX
2. LF
3. SZZ
4. HCQ
2
avoid SZZ use if CrCL
<30
SZZ onset and max eff
onset 8-12wks, max eff 6mths
SZZ is often used in combo with
MTX, HCQ
SZZ CIs
1. sulfonamdie allergy
2. salicylate allergy
3. both
sulfonamide allergy only - salicylate allergy can be desensitized
common SZZ SEs include
nausea, dyspepsia, diarrhea (use enteric coated tablet), photosensitivity (sunscreen), rash, HA, dizziness
HCQ onset and max eff
onset 12-16wks, max eff 6mths
what is the mildest and best tolerated DMARD
1. MTX
2. LF
3. SZZ
4. HCQ
4
avoid HCQ if CrCL
<30
caution should be used with HCQ if the pt has a hx of
1. depression
2. diabetes
3. HPTN
4. dyslipidemia
2- risk of hypoglycemia
what are some first signs of HCQ eye toxicity
loss of red light perception
RFs for HCQ mediated eye toxicity
> 60yrs, hx ocular diseases, renal/ liver dysfunction
how to monitor for HCQ eye toxicity
baseline, 5yrs (if no RFs/ sx), annual if high risk (older, sx)
V extensive, pictures taken, dilation (must check if optometrist doing this)
what are 3 “other” DMARDs that are not often used anymore
gold salts
minocycline
azathioprine, cyclosporine, cyclophosphamide, mycophenolate
T or F: scDMARDs can increase the risk of infections
F- but may last longer or seem worse- only d/c DMARD if severe/ on MD advice
can scDMARDs be continued when pt needs surgery?
yes- usually
bDMARDs and txDMARDs are utilized in those
with inadequate response to at least 2 csDMARDs (mono/combo) after 3mths at target dose
what is usually the initial advanced therapy one could use after csDMARD failure
TNFi
what is primary failure to TNFi? what should be done?
No response to TNFi: switch to alt bDMARD or tsDMARD, do not retry another TNFi
what is secondary failure to TNF? what should be done?
ail TNFi after years = switch to alt TNFi, other b/tsDMARD
how do bDMARDs work?
block specific pts of immune system- targeted therapy
bDMARDs have
1. increased damage
2. reduced sc and CV risk
3. increased CV risk
4 .increased infection risk
4
T or F: when using bDMARDs, MTX should still be included
T- MTX still anchor to improve effectiveness + to avoid antibody formatio nto the biologic proteins
TNFi onset and peak
onset 2wks
peak 3-6mths
TNFi CIs
HF (NYHA class III-IV), MS (personal hx maybe also 1st degrees relatives), active cancer (caution: hx of lymphoma or skin), may also trigger lupus like sx, psoriasis
pick all that apply, whcih of the following must be used with MTX
1. adalimumab
2. certolizumab
3. golimumab
4. etanercept
5. infliximab
3, 5
abatacept MOA
T cell costimulation modulator- mimics CTLA4 = prevents CD28 from binding to CD80/86 = enables T regulatory activity to continue = lower T cell immune mediated cascade by blocking 2nd signal = decreases inflammation
onset and peak of abatacept
onset 2-4wks, peaks 3-6mths
abatacept is used in _____RA who ____
mod-severe RA who fail TNFi
abatacept may incerase the incidence of
AECOPD and pneumonia
tocilizumab and sarilumab are
IL6i
IL6- onset and peak
onset 2-4wks, peak 3-6mths
IL6i caries the rare but serious risk of
GI perforation is there is a hx of diverticulities
what increases the risk of GI perf with IL6i
hx of diverticulitis, NSAIDs, prednisone
how does IL6i interact with CYP enzymes
down regulates it
rituxumab class
B cell inhibitor
rituximab onset and peak in RA
onset 8wks, peak 4-6mths
rituximab is the preferred biologic in pts with
B cell lymphoma, latent TB infection, MS, concomitant vasculitis or overlap syndromes
URTI is more common in the first year with ____
TNFi
allerguic reactions to RTX can be premedicated with
acetaminophen, cetirizine/ loratadine, +- metylprednisone
T or F: bDMARDs increase the risk of solid tumors and lymphoma
F- MTX and bDMARDS may be associated with a small risk
T or F: biosimilars are different in each batch
T
what is required to compare the biosimilar to the reference product?
at least 1 clinical study to see that there are no clinically meaningful differences between biosim and originator
JAKi MOA
small molecule inhibitor of JAK induced cytokine production
Tofacitinib, upadacitinib, baricitinib are all
JAKi
onset and peak of JAKi
onset 2-4wks, peak 3-6mths
caution with JAKi
risk of GI perforation of hx diverticulitis (RF: NSAIDs, prednisone)
4 common SEs for JAKi
URTI, nasopharyngitis, HA, diarrhea
which JAKi has a signal with VTE
baricitinib = CV events and cancers under postmarketing surveillance
T or F: tofacitinib met noninferiority compared to TNFi for risk of CVD
F- was slightly higher + crossed line of no effect
what should you do with bDMARDs and txDMARDs during infection?
hold until 48hrs after abx complete/ sx resolved (including for topical infections)
how to prevent infection on bDMARDs/ tsDMARDs
vaccinate 4wks prior to initiation + avoid LIVE vaccines
should you hold b/ts DMARDs for a cold?
no- may consider if severe
what to do with b/ts DMARDs in the perioperative times
hold per and post op to decrease risk of infection + ensure appropriate healing
Timing dependent on bDMARD and the operation
what are steroids and NSAIDs used for in RA
managing flares, as bridging tx while awaiting DMARD onset, sx control if no other options exist
are steroids and NSAIDs ever used in initial RA treatment?
yes
oral or IM steroids and NSAIDs in RA are useful for
managing sx in many joints
intraarticular steroids are useful in RA for
controlling residual synovitis in a single joint, tendon, bursa with less systemic toxicity
when only 1-2 joints inflammed
how long does it take IA steroids to kick in? how long does it last?
relief onset in few days, lasts wks to months
what is a major pro of IA steroids
may help avoid steroid cycling
RA adjunct tx may include
analgesics (APAP,. Opioids, cannabis), antiinflammatories; NSAIDs (PO/ topical), NHPs
T or F: if NSAIDs, opioids, and cannabis have not relieved RA pain within a month, it is unlikely to work ever
T
which 3 NHPs may be used in RA
omega 3s
calcium/ vit D
should an RA patient use immune boosters like gingseng and echinacea to prevent infection
no
vaccine efficacy is most reduced with ___, ____, ____
MTX, prednisone, RTX
what are the vaccine guidelines for csDMARDs
Inactivated vaccines considered safe
Some live vaccines considered safe- MMR booster
what are the vaccine guidelines for bDMARDs and tsDMARDs
Inactivated vaccines considered safe
Live vaccines CI
what to do with influenza vaccine and MTX
Hold methotrexate for 2 wks after vaccination only if disease allows
what to do with influenza vaccine and RTX
Continue rituximab, give influenza vaccine on schedule (delay subseq rit dose F2wks if disease state allows)
what to do with other nonlive attenuated vaccinations and RTX
Time vaccination for when next rituximab dose is due, then hold rituximab for at least 2 wks after vaccination
what to do with MTX and other nonlive attenuated vaccines
continue as normal
