Rheumatoid Arthritis Flashcards
Describe the basic pathophysiology of RA.
infiltration of synovium by immune cells that release cytokines that proliferate damaging immune response in joint
Define pannus.
A pannus is a proliferating, inflamed joint that eventually invades/destroys cartilage and bone.
Diagnosis of RA is determined by a score of ___ points or more in what 4 diagnostic criteria?
6 points or more
1) joint involvement
(2) serology
(3) duration of symptoms
(4) acute phase reactants (CRP and ESR
5 most common joints affected by RA
hips, knees, ankles, elbows, shoulders
Name some extra-articular manifestations of RA.
(1) rheumatoid nodules
(2) ocular
(3) cardiac
(4) pulmonary
(5) vasculitis
(6) Felty’s syndrome (splenalomegaly)
Which two serologic measures are most specific to RA and are most often present in someone with the disease?
anti-CCP and RF
What is joint aspiration?
turbidity of synovial fluid
What kinds of characteristics generally indicate a poor prognosis in somebody with RA?
low socioeconomic status, poor education, psychosocial stress, extra-articular manifestations, elevated CRP/ESR, high RF titers, erosions observed in x-ray, present in >20 joints
Contrast RA from OA.
see table in notes: differentiating criteria include age of onset, disease distribution, ESR, inflammation level, morning stiffness, osteophyte/pannus presentation, swelling, and typical presentation
Identify non-pharmacological treatment options for RA.
(1) rest
(2) splints/prosthetics (for deformities)
(3) PT/OT
(4) emotional support
(5) weight reduction
(6) surgery
(7) pt. education
What is the role of NSAIDs/COX-2 inhibitors in RA pharmacotherapy?
adjunct therapy: only help with pain, but do not alter disease progression, therefore should not be used as monotherapy
use anti-inflammatory doses (generally 2x analgesic doses)
dosing of Celebrex (celecoxib)
100-200 mg PO BID
Patients with what allergy should be carefully monitored with Celebrex use?
those with a sulfa allergy
What are the 4 different ways that corticosteroids can be used in RA patients?
(1) burst therapy: to treat an acute flare-up
(2) bridge therapy: in combination with a DMARD while you wait for its onset
(3) long term low dose: for advanced disease
(4) for patients with extra-articular manifestations
note: NOT as monotherapy
Using prednisone as an example, what would be considered a short term, low dose regimen of oral CS?
< 10 mg QD for less than 3 months
What is the max recommendation of a high daily dose of prednisone?
60 mg QD
adverse effects of oral CS
(1) hyperglycemia
(2) irritability
(3) elevated BP
(4) gastritis
monitoring parameters for oral CS use
BP and glucose ever 3-6 months
Which class of drugs can be used as monotherapy in RA due to their ability to decrease and prevent joint damage and preserve joint integrity?
DMARDs
What is the DMARD of choice in RA patients? How is it dosed?
Rheumatrex (methotrexate)
initial dose is 7.5 mg weekly, but can be increased to 15 mg weekly
What supplementation is recommended with methotrexate use?
folic acid (MOA of drug is inhibition of dihydrofolic acid reductase, depleting folate)
Which two DMARDs cannot be used in pregnancy?
Sulfasalazine, Methotrexate
monitoring parameters for MTX use
CBC, SCr, LFT
frequency depends on duration of therapy:
<3 months: every 2-4 weeks
3-6 months: every 8-12 weeks
>6 months: every 12 weeks
adverse effects of methotrexate
hepatic issues, hematologic, gastrointestinal, dermatologic, ocular, teratogenic
contraindications to methotrexate therapy
pregnancy, immunodeficiency, pre-existing blood dyscrasia, chronic liver disease
leflunomide dosing
100 mg PO QD for 3 days, then 20 mg QD
can reduce to 10 mg QD if adverse effects
leflunomide time to onset
1 month
Use caution with leflunomide if:
patient is also using methotrexate (increased risk of liver toxicity)
leflunomide adverse effects
diarrhea, teratogenic, rash, alopecia, increased LFTs
Which two DMARDs are prodrugs?
leflunomide and sulfsasalazine
leflunomide monitoring parameters
CBC, SCr, LFTs every
< 3 months: every 2-4 weeks
3-6 months: every 8-12 weeks
> 6 months: every 12 weeks
sulfasalazine dosing
500 mg PO QD up to 1 g 2-3x QD
sulfasalazine time to onset
1-2 months
sulfasalazine adverse effects
dermatologic, gastrointestinal, hematologic
sulfasalazine monitoring
CBC, SCr, LFTs
< 3 months: every 2-4 weeks
3-6 months: every 8-12 weeks
> 6 months: every 12 weeks
Use caution with sulfasalazine in patients who:
have a sulfa allergy
Hydroxychloroquine (Plaquenil) dosing
200 mg PO BID
Hydroxychloroquine time to onset
2-4 months
Plaquenil adverse events
ocular, gastrointestinal, dermatologic
Plaquenil monitoring
advantage: no extensive regular lab work required, just an ocular exam ever 6-12 months
What are some of the risks associated with BRM therapy?
(1) can exacerbate existing heart failure
(2) increased susceptibility to infections, particularly TB
(3) demyelinating disorders
(4) malignancies
(5) no concurrent vaccine treatment
adverse effects of BRM therapy
(1) injection site reactions
(2) headache and rash
(3) CHF exacerbations
(4) risk of malignancy and demyelinating disease
Etanercept (Enbrel) dosing
50 mg SC weekly
These anti TNFs do not require lab monitoring.
Enbrel, Remicade, Humira, Cimzia
This anti TNF does require lab monitoring (which labs?)
Simponi (Golimumab)
CBC with platelets, LFTs
Which anti TNF agents are only indicated for RA in combination with MTX?
Remicade, Golimumab
What testing is recommended before initiation of an anti-TNF agent?
TB skin test
Which anti-TNF agents can be used either alone or in combination with a non-BRM DMARD?
Enbrel, Humira, Cimzia
Anakinra (Kineret) MOA
IL-1 receptor antagonist
Anakinra (Kineret) indication
for patients with moderate to severe RA with an inadequate response to one or more DMARD
can be used alone or in combination with DMARDs other than BRMs
Humira dosing
40 mg SC every other week
Simponi dosing
50 mg SC monthly
Infliximab dosing
3 mg/kg at 0, 2, 6 weeks, then every 8 weeks
Certolizumab dosing
2 200 mg SC injections at 0, 2, and 4 weeks, then either:
(1) 200 mg SC every 2 weeks
(2) 400 mg SC every 4 weeks
Anakinra dosing (normal and CrCl < 30 mL/min)
100 mg SC QD
if CrCl < 30 mL/min, 100 mg SC QOD
Kineret should not be used with what other class of drugs?
anti-TNF or T-cell costimulation modifier (abatecept)
How is Kineret dosed?
by weight, but all doses are given IV over 30 minutes
doses given at 0, 2, and 4 weeks, then every 4 weeks thereafter
Anakinra adverse effects
HA, nausea, upper respiratory issues, infusion rxns, serious infection, malignancy
Anakinra precautions/warnings
not for use with with TNF antagonist or IL-1 antagonist
increased risk for infections (caution in COPD patients)
no concurrent live vaccination administration
Which BRM is an IL-6 receptor antagonist?
Tocilizumab (Actemra)
Actemra dosing
4 mg/kg IV over 1 hour
Actemra monitoring parameters
neutrophil count, platelet count, LFTs all every 4-8 weeks
lipid panel after 4-8 weeks, then every 6 months thereafter
Tocilizumab adverse effects
(1) infections
(2) liver toxicity
(3) thrombocytopenia
(4) neutropenia
(5) lipid abnormalities
(6) intestinal perforations
Rituximab is indicated for use in combination with ____
methotrexate
Rituximab dosing
two infusions separated by two weeks, can repeat dosing in 6 months
Rituximab is indicated for use in which type of patients?
moderate to severe RA in patients with inadequate response to one or more TNF antagonist
What are the three most common combinations of therapy in RA treatment?
(1) MTX + HCQ/SSZ (or all three)
(2) MTX + leflunomide
(3) MTX + BRM
