Rheumatoid Arthritis Flashcards by Bradley Wuthrich

Describe the basic pathophysiology of RA.

infiltration of synovium by immune cells that release cytokines that proliferate damaging immune response in joint

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Define pannus.

A pannus is a proliferating, inflamed joint that eventually invades/destroys cartilage and bone.

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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

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5 most common joints affected by RA

hips, knees, ankles, elbows, shoulders

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Name some extra-articular manifestations of RA.

(1) rheumatoid nodules
(2) ocular
(3) cardiac
(4) pulmonary
(5) vasculitis
(6) Felty’s syndrome (splenalomegaly)

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Which two serologic measures are most specific to RA and are most often present in someone with the disease?

anti-CCP and RF

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What is joint aspiration?

turbidity of synovial fluid

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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

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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

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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

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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)

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dosing of Celebrex (celecoxib)

100-200 mg PO BID

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Patients with what allergy should be carefully monitored with Celebrex use?

those with a sulfa allergy

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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

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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

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What is the max recommendation of a high daily dose of prednisone?

60 mg QD

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adverse effects of oral CS

(1) hyperglycemia
(2) irritability
(3) elevated BP
(4) gastritis

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monitoring parameters for oral CS use

BP and glucose ever 3-6 months

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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

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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

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What supplementation is recommended with methotrexate use?

folic acid (MOA of drug is inhibition of dihydrofolic acid reductase, depleting folate)

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Which two DMARDs cannot be used in pregnancy?

Sulfasalazine, Methotrexate

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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

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adverse effects of methotrexate

hepatic issues, hematologic, gastrointestinal, dermatologic, ocular, teratogenic

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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