Gout/Rheumatoid Arthritis

Question 1

DMARD

• Folate antagonist
• Benefits appear to be the result of immunosuppression secondary to reducing the activity of B and T lymphocytes
• Major toxicities are hepatic fibrosis, bone marrow suppression, GI ulceration, and pneumonitis
• Supplemental folic acid recommended
• Contraindicated in women who are pregnant or nursing, patients with blood dyscrasias, immunodeficiency, and liver disease

Answer 1

Methotrexate

Question 2

DMARD

• Powerful immunosuppressant indicated for adults with active RA
• Potentially more hazardous and expensive than MTX; therefore, used as second-line
• Prodrug that undergoes conversion to its active form—metabolite 1 (M1)—in the body; inhibits T-cell proliferation
• Hepatotoxicity, nausea, rash, SJS, myelosuppression, alopecia
• Teratogenic

Answer 2

Leflunomide

Question 3

DMARD

• Also used for IBD treatment
• Benefits for RA may result from antiinflammatory and immunomodulatory actions
• Adverse effects: GI effects, dermatologic reactions, hepatitis and immunologic reactions rare
• Contraindicated in patients with sulfa allergy

Answer 3

Sulfasalazine

Question 4

DMARD

• Antimalarial action
• Full therapeutic effects take 3 to 6 months to develop
• MOA unknown; but does not slow disease progression
• Adverse effects: retinal damage, cardiac damage, GI distress

Answer 4

Hydroxychloroquine

Question 5

• Suppresses inflammation by inhibiting TNF
• Indicated for patients with moderately to severely active RA
• Also is approved for ankylosing spondylitis, plaque psoriasis, psoriatic arthritis, and juvenile idiopathic arthritis
• Injection site reactions, serious infections, severe allergic reactions, heart failure, cancer, hematologic disorders, liver injury, and central nervous system (CNS) demyelinating disorders

Answer 5

Etanercept

Question 6

• TNF antibody
• Approved for combined use with methotrexate to reduce symptoms and delay disease progression
• Has immunosuppressant actions that can increase the risk for serious infection, including bacterial sepsis, invasive fungal infections, HBV infection, and TB
• Infusion reactions are common, manifesting with flu-like symptoms, headache, fever, chills, dyspnea, hypotension, skin reactions, and GI disturbance

Answer 6

Infliximab

Question 7

• Is indicated for adults with moderate to severe RA who have not responded adequately to one or more DMARDs
• May be used alone or in combination with methotrexate or other DMARDs
• Can promote serious infections (e.g., bacterial sepsis, invasive fungal infections, HBV infection, TB) and has been associated with rare cases of heart failure, liver failure, hematologic disorders, neurologic disorders, severe allergic reactions, and cancer

Answer 7

Adalimumab

Question 8

T-Cell Activation Inhibitor

• Binds with receptors on APCs and thereby prevents the APCs from activating T cells
• Two approved indications: to reduce symptoms and delay disease progression in adults with moderately to severely active RA, and to decrease symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children 6 years of age and older
• Can increase the risk for serious infections and blunt effects of vaccines

Answer 8

Abatacept

Question 9

Interleukin-6 Receptor Antagonist

• Typically used only for those patients with RA who have not responded adequately to other DMARDs
• May be combined with methotrexate but not with TNF inhibitors or other DMARDs that increase the risk for infection
• Most serious adverse effects are infections, GI perforation, liver injury, and hematologic effects: neutropenia and thrombocytopenia

Other drug in category is Sarilumab

Answer 9

Tocilizumab

Question 10

Interleukin-1 Receptor Antagonist

• It reduces symptoms of RA by blocking receptors for IL-1, a proinflammatory cytokine that plays a central role in synovial inflammation and joint destruction
• Drug is indicated for patients with moderate to severe RA that have not responded to one or more conventional DMARDs (e.g., methotrexate)

Answer 10

Anakinra

Question 11

Janus Kinase Inhibitors

• Prevents activation of the STAT pathway by preventing JAK enzyme signaling
• Indicated for treatment of moderately to severely active RA in patients who cannot take methotrexate and for patients who have not experienced an adequate response to methotrexate
• Other common adverse effects include headache, increased serum cholesterol, increased creatine phosphokinase, and skin rashes

Answer 11

Tofacitinib/Baricitinib

Question 12

• Can be used short term to treat an acute gouty attack. Second, it can be used long term to prevent attacks from recurring
• It may work, at least in part, by inhibiting leukocyte infiltration; it accomplishes this by disrupting microtubules, the structures required for cellular motility
• Narrow therapeutic index
• Disruption of cell division in the GI tract and bone marrow underlies the drug’s major toxicities
• should be used with care in older adults and debilitated patients and in patients with cardiac, renal, hepatic, and GI disease

Answer 12

Colchicine

Question 13

Xanthine Oxidase Inhibitor

Its major metabolite (alloxanthine) inhibits xanthine oxidase (XO), an enzyme required for uric acid formation
* Mild side effects include GI reactions (nausea, vomiting, diarrhea, and abdominal discomfort) and neurologic effects (drowsiness, headache, and metallic taste)
* Serious but less common adverse effects include bone marrow suppression, hepatotoxicity, and hypersensitivity
* HLA-B5801 testing

Alternative is Febuxostat

Answer 13

Allopurinol