RA

rheumatoid arthritis

considered an autoimmune disease in which the body loses its ability to distinguish between synovial and foreign tissue

human leukocyte antigen DR4 (HLA-DR4)

this genetic marker has been associated with triggering the inflammatory process in RA

• T lymphocytes

Antigen-dependent activation of ______ leads to proliferation of the synovial lining, activation of proinfl ammatory cells from the bone marrow, cytokine and protease secretion, and autoantibody production

Anticitrullinated proteins and peptides

these kinds of proteins and peptides are high specific for RA

• Tumor necrosis factor a (TNF-a)

• IL-1

• IL-6

• IL-8

• growth factors

these factors propagate the inflammatory process in RA

Inflamed synovium

hallmark of the pathophysiology of RA

• pannus

• articular cartilage

• subchondral bone

In an inflamed synovium, it proliferates abnormally, growing into the joint space and into the bone, forming a _______. This migrates to the ______ and into the ______ leading to destruction of cartilage, bone, tendons, and blood vessels

• MCP

• PIP

• MTP

• wrists

first commonly affected joints by RA (4)

• 4

• first

Within _____ months of diagnosis, irreversible joint damage is detectable on radiographic images. The rate at which joint damage occurs is greatest during the _____ year

Rheumatoid factor (RF)

• found in 60% of patients with RA

• If initially negative, the test can be repeated in 6 to 12 months

• not an accurate measure of disease progression

• Erythrocyte sedimentation rate (ESR)

• C-reactive protein (CRP)

• 2 markers of inflammation and are usually elevated in patients with RA

• help indicate the activity of the disease, but do not indicate disease severity

Anticyclic citrullinated peptide antibodies (ACPA)4

found in most patients with RA and are useful in predicting erosive disease

• Joint involvement

• Serology

• Acute phase reactants

• Duration of symptoms

4 domains of criteria of RA

Radiographic examination

diagnostic test that can reveal the extent of bone erosion and cartilage loss

MRI

diagnostic test that can detect proliferative pannus

corticosteroids

• excellent anti-inflammatory activity

• immunosuppressant

• lowest effective dose for adverse effects

• slows joint damage

• often used as “bridge” therapy as patients start on disease-modifying antirheumatic drugs (DMARDs) or during an acute RA flare

Nonbiological disease-modifying antirheumatic drugs (NBDMARDs)

• used to reduce or prevent joint damage and preserve joint function

• considered within 3 months of diagnosis

Methotrexate

• NBDMARD that works by inhibiting dihydrofolate reductase

• considered standard therapy for RA

• recommended for all patients with RA regardless of disease duration, disease burden, or prognostic factors.

folic acid

Methotrexate used alongside ____ may reduce its side effects

Leflunomide

• NBDMARD that inhibits pyrimidine synthesis

• recommended for all patients with RA regardless of disease duration, disease burden, or prognostic factors

cholestyramine

recommended as a binding agent if serious toxicities occur or if the patient wishes to become pregnant when taking leflunomide

Sulfasalazine

• NBDMARD cleaved by bacteria in the colon into sulfapyridine and 5-aminosalicylic acid

• recommended for all disease durations and degrees of illness without poor prognosis

Hydroxychloroquine

• NBDMARD; unknown MOA

• recommended for those without poor prognosis and low disease activity of < 2 years

Biological DMARDs

• can reduce or prevent joint damage, preserve joint integrity and function in patient with moderate to severe RA

• used primarily in those failing an adequate trial of one or more NBDMARDs or in patients with high disease activity and poor prognosis

TNF-a blockers

• BDMARD that inhibits the inflammatory response mediated in immune cells

• recommended if high disease activity is present early in the course of the illness ( 3 months) with poor prognosis

• considered when patients do not achieve an acceptable response to MTX or other NBDMARDs

• Etanercept

• adalimumab

• certolizumab

3 TNF-a blockers that can be used as monotherapy or in conjunction with MTX

• Infliximab

• golimumab

2 TNF-a blockers that is only FDA approved for use with MTX in RA

Abatacept

• BDMARD that is the first T-cell costimulation blocker

• It is used as monotherapy or NBDMARDs

• recommended with MTX NBDMARD does not work in the presence of moderate disease with poor prognosis

Rituximab

• BDMARD that is anti-CD20 monoclonal antibody

• used when the patient fails MTX and/or multiple DMARDs and has high disease burden and poor prognosis

• CD20+

• chronic synovitis

Use of rituximab causes depletion of _____ cells and affect the autoimmune response and helps with the _____ associated with RA

Anakinra

• BDMARD that is an IL-1 receptor antagonist

• used as monotherapy or in conjunction with any DMARD except a TNF-blocker

Tocilizumab

• BDMARD that is an IL-6 receptor monoclonal antibody

• indicated for moderate to-severe RA in adults who have not achieved response with one or more TNF-antagonists

• used as monotherapy or with MTX or other NBDMARDs

• MTX + HCQ

• MTX + sulfasalazine

• MTX + leflunomide

• sulfasalazine + HCQ + MTX

4 combination therapies supported

Surgical treatment

intervention considered when pain is severe, range of motion is lost, or joint function is poor