Saad - Rheumatoid Arthritis Part 2 Flashcards
MOA of methotrexate
inhibits DHFR
what is the DMARD of choice for most patients
is it used alone or in combination with other DMARDS
methotrexate
can be either monotherapy or in combo with other DMARDS
around how long does it take to see the clinical benefits of MTX
3-6 weeks
how is methotrexate dosed
why is this a concern
WEEKLY – NOT QD
can very easily not read the directions correctly and OD causing blood toxicity and other toxicity
what is max dose methotrexate/week for RA
20-25 mg
is renal dose adjustment required for MTX
yes
name 5 scenarios in which methotrexate is CONTRAINDICATED
teratogenic - no pts who are pregnant or breastfeeding
alcoholism
alcoholic/chronic liver disease
immunodeficiency
hematologic disorders like leukopenia (INC INFECTION RISK) or thrombocytopenia (platelets) - BLEEDING
what is methotrexate supplemented with and why
FOLIC ACID
usually greater than 5mg a day
to reduce adverse events from methotrexate
name some adverse effects of methotrexate
GI – NVD, anorexia, dyspepsia
mucosistis (mouth and GI ulceration)
liver fxn abnormalities
in a patient CURRENTLY taking methotrexate, what should they be monitored for
CBC, ALT, AST (liver), renal functio
what is done in pts with an underlying LUNG DISEASE about to start MTX
a chest xray
what kind of screenings must be done before MTX is intitiated
in high risk pts - hep b and c (do NOT want further liver toxicity from MTX) and tb screeenings
***important consideration regarding leflunomide and why
it has a very long half life (2 weeks)
therefore, if allergic or experience some toxic effects, it is more of a concern
give cholestyramine if need to wash out bc of toxic effects or a pregnancy the pt wasnt aware of – its teratogenic like MTX
what is an alternative to MTX in pts who cannot tolerate or dont get benefit from it
leflunomide
MOA of leflunomide
inhibits pyrimidine synthesis
inhibits T cell response to some stimuli
halts the cell cycle
around how long to see efficacy after taking leflunomide
1 month
how does the monitoring when taking leflunomide compare to methotrexate
BASICALLY SAME
ALT/AST, CVC, renal function
should get TB screening, CBC with diff prior to start
name 3 scenarios in which leflunomide is CONTRAINDICATED
pregnancy
impaired liver fxn (inc hep b/c)
sevre immunocomp pts
true or false
leflunomide is HIGHLY TERATOGENIC, even after discontinuation
TRUE
name some AE of leflunomide
GI - NVD, anorexia, cramps
inc liver fxn tests, liver failure
myelosuppression when combined with other treatment
when educating a patient who is taking leflunomide, name 3 points to mention
stay hydrated
report GI symptoms like NVD or jaundice immediately
report sign of infection
hydroxychloroquine brand
plaquenil
explain the mechanism of hydroxychloroquine
has anti inflammatory properties by interfering with macrophages and other APC’s and their antigen processing
what is the role of hydroxychloroquine in RA
use in mild RA in combination therapy – for those who can’t tolerate MTX
what is the biggest concern with ppl taking hydroxychloroquine***
there is a LIFETIME MAX DOSE due to ocular side effects
must get eye exams bc of ophthalmic toxicities
name some ocular toxicity effects of hydroxychloroquine
blurred vision
night blindness
retinal damage
loss of vission
name some neurologic side effects of hydroxychloroquine
mild – headache, vertigo, insomnia
dermatologic side effects of hydroxychloroquine
rash alopecia hyperpigementation
what is sulfasalazine
another DMARD that is used if MTX can’t be tolerated.
it is a prodrug
sulfasalazine has ___ and ____ properties
immunomodulating AND anti-inflammatory properties
what are the 2 metabolites of the prodrug sulfasalazine
5-ASA (aminosalicylic acid) and sulfapyridine
can sulfasalazine be used in pregnant and nursing moms
it does cross placenta and is present in breast milk
however, it can be used with caution
name 2 contraindications for sulfasalazine
allergy to sulfonamide or salicylate
what is a main side effect of sulfasalazine
urine and skin discoloration - can turn orange or yellow
name 2 OA/RA drugs that are contraindicated in those with sulfa allergy
celecoxib and sulfasalazine
in the 4 DMARDS discussed (MTX, leflunomide, hydroxychloroquine, and sulfasalazine)
when is the most frequent monitoring done?
within 3 months of starting therapy - done 2-4 weeks
after that it continually decreases, with it being done every 12 weeks after 6 months of taking
BIOLOGIC DMARDS are associated with an increased risk of what and why?
risk of infection bc of their immunosuppressant effects
therefore, TB skin test or IGRA blood test is done to detect and treat latent or active tb
should also be screened for Hep B and C - risk of reactivation
true or false
biologic agents cannot be used in combination with conventional DMARDS
FALSE - they can
true or false
biologics can NOT be given with another biologic
true
they have additive immunosuppressant effects - dangerous
if patients dont have success with a biologic, what is the next course of treatment
try a different biologic – never use 2 at once
what is the mechanism of TNFa inhibitor biologics
block TNFa, a proinflammatory cytokine
when would a biologic TNFa inhibitor be used in an RA patient
when, despite conventional/synthetic DMARD therapy, the disease activity is still mod-high
**contraindication for TNFa inhibitors
those with moderate-severe heart failure
new onset or worsened heart failure has been reported
what is a big concern with TNFa inhibitor biologics, besides being contraindicated in heart fialure patients
they can increase the risk of serious infection and MALIGNANCIES like lymphoma or skin cancer
also, multiple sclerosis, a demyelinating disroder, has occurred
before starting TNFa inhibitors, patients should be screened for what
TB and hep B and C
DURING TNFa therapy, what should be monitored periodically and why
CBC with differential – bc they can cause blood disorders like pancytopenia (lower RBC, WBC, platelets)
also watch for signs of malignancy and serious infectionse
name the 2 BBW for TNFa antagonists
malignancy, specifically hepatosplenic T cell lymphoma (HSTCL)
FATAL INFECTIONS - opportunistic infections like legionella and listeria
true or false
JAK inhibitors can be used in combo with a biologic DMARD or JAK inhibitor
FALSE
can be used with synthetic/conventional DMARD, but not another biologic OR JAK INHIBITOR. way too potent
explain how JAK inhibitors function
they bind the catalytic portion of JAK and block the messaging pathway of multiple pro-inflam cytokines
can JAK inhibitors be used by themselves (monotherapy)
yes
can JAK inhibitors be used with other JAK inhibitors
NO
black box warnings for JAK inhibitors
serious infections
malignancies
CLOTS – DVT, PE, thrombosis
TB testing is recommended prior to treatment with WHAT 3 THINGS
biologics
methotrexate
leflunomide
if a TB infection occurs while on MTX/leflunomide/biologics - what should be done
temporarily discontinue until infection is cured
are JAK inhibitors biologics
NO
kind of like a “targeted” synthetic - not conventional synthetic like MTX
a patient with a history of significant TB exposure or recurrent TB infection may not be a candidate for which drugs
MTX, leflunomide, biologics
if a patient has an active or latent TB infection and is looking to start MTX or leflunomide or biologics, what must be done?
they get antitubercular treatment
treatment with biologics can start after ONE MONTH of latent TB treatment with meds and after completing treatment of active TB (as applicable)
ALL PATIENTS receiving DMARDS should get what 4 vaccinations
influenza
pneumonia
HPV
herpes zoster (NOT THE LIVE ONE)
If a patient gets the LIVE herpes zoster vaccine, how long do they have to wait before starting biologics
2 weeks
the hepatitis B vaccine is reccomended to certain patients getting biologic OR nonbiologic DMARDS
name these 3 populations
healthcare workers
those who use IV drugs
those who have mult sex partneers
name 3 live vaccines that can NOT be given to patients on biologics
MMR
yellow fever
LIVE herpes zoster
4 patient populations with high risk comorbidities
hepb/c
congestive heart failure
malignancy
serious infections
a patient has an active hep B infection and is receiving effective treatment for it
what kind of RA therapy should they get
what about a patient with chronic hep B who is UNTREATED
same as someone who doesnt have the infection
UNTREATED - refer to antiviral therapy before getting immunosuppressants
pt with Hep C infection and receiving effective treatment - what RA therapy should they get??
pt with hep C infection NOT getting antiviral treatment, what should they get
same as someone without condition
if not being treated - reccomend DMARD over TNFa antagonist
which RA therapy is CONTRAINDICATED in congestive heart failure patients
TNFa antagonists
if a patient is taking TNFa antagonist and devleops signs of worsening heart failure, what should be done
discontinue therapy and recommend combination DMARDS, non TNF biologics, or tofaticinib
in general, patients with treated or untreated skin cancer or lymphoma disorders, what is recommended
which type of treated cancer gets treated the same
DMARDS over biologics
solid organ malignancy
patients with previous serious infections should use ___ over ____ and ______ over ______
DMARDS over TNFa antagonists
abatacept over TNFa antagonists
synthetics preferred over biologics
it is recommended that patients _____________ for at least 6 months prior to tapering down the dose
at target – low disease activity or remission
true or false
it is recommended to abruptly discontinue DMARDS
false - gradual tapering is preferred
just reducing the dose is even better
explain what a biosimilar is
a biologic product HIGHLY SIMILAR to a reference product
no clinically meaningful differences in efficacy/adverse effects/immunogenicity
what is the treatment for NODULES - an extra-articular manifestation of RA
NONE
what is the treatment for vasculitis - an extra-articular manifestation of RA
aggressive treatment of the inflammatory process
what is the treatment for ocular extra-articular manifestations of RA
(keratoconjunctivitis sicca of sjogren’s syndrome)
articifical tears
what is xerostomia
dry mouth
an extra-articular maifestation of RA
how is xerostomia treated
pilocarpine or cevimeline
