Drugs for RA

Question 1

What are the therapeutic goals for treating RA?

Answer 1

• Relieve pain
• Reduce inflammation
• Slow down or stop joint damage
• Improve a person’s sense of well being and ability to function

Question 2

Have minimal effect on progression of joint deformity

Used in large doses for long duration of treatment

Relieve symptom pain

Answer 2

NSAIDs

Question 3

What does DMARDs stand for?

Answer 3

Disease-Modifying Anti-Rheumatics

Question 4

Inhibits the ability of TNF-a to bind to its receptor

Recombinant fusion protein

Answer 4

Etanercept

Question 5

Pharmacokinetics of Etanercept.

Answer 5

IV or subcut administration

Onset of action 1-2 weeks

Elimination half life > 3 days

Question 6

Adverse effects of Etanercept

Answer 6

Injection site reactions
Increase risk of infections (screen for latent TB before beginning treatment and closely monitored during and after drug therapy)

Lymphomas in children/adolescent patients

Question 7

What is etanercept therapeutically used for?

Answer 7

Moderate to severe RA

Juvenile RA

Early stage

Question 8

IgG monoclonal antibody (human)

Binds to soluble AND transmembrane forms of TNF-a

Prevents TNF-a binding to its receptor

Answer 8

Adalimumab

Question 9

How and how often is Adalimumab administered?

Answer 9

Subq

Every other week

Question 10

Adverse effects of Adalimumab

Answer 10

Injection site reactions

Increased risk of infections

Lymphomas in children/adolescent patients

Question 11

What are the therapeutic uses of Adalimumab?

Answer 11

Active RA (moderate to severe); may be used alone or in combination with methotrexate or other DMARDs

Active juvenile idiopathic arthritis (moderate to severe); may be used alone or in combo with methotrexate

Question 12

How does Infliximab and Adalimumab differ from Etanercept in regards to binding TNF-a?

Answer 12

Infliximab and Adalimumab can bind to both m-TNF and s-TNF, neutralizing their biologic activity – may also induce apoptosis of the expressing cells

Etanercept also neutralizes s-TNF but does not bind to m-TNF or induce apoptosis of expressing cells

Question 13

Humanized antibody, binds to soluble and membrane bound IL-6 receptors

Inhibits IL-6 mediated signaling via these receptors

Answer 13

Tocilizumab

Question 14

How often is Tocilizumab administered?

Answer 14

IV every 4 weeks

SubQ every other week

Question 15

Adverse effects to Tocilizumab

Answer 15

Injection site reactions

Increased risk of infections

Alterations in lipid profile – increases in total cholesterol, triglycerides, LDL, and/or HDL

Question 16

What is Tocilizumab therapeutically used for?

Answer 16

Indicated for adult patients with moderatly to severely active RA who have had an inadequate reponse to one or more TNF antagonists

Question 17

Janus kinase (JAK) inhibitor

Answer 17

Tofacitinib

Question 18

How is Tofacitinib metabolized?

Answer 18

Administered orally

Metabolism mediated by CYP3A4 with minor contribution from CYP2C19

Question 19

Adverse effects of Tofacitinib

Answer 19

Increase risk of infections

Increase in cholesterol

Question 20

How is Tofacitinib therapeutically used?

Answer 20

For treatment of moderately to severely active RA in patients who are unable to take methotrexate

May be used as monotherapy or in combo with methotrexate or other DMARDs

Question 21

Sites of action of drugs:

1. Abatacept
2. Methotrexate and Leflunomide
3. Etanercept, Infliximab, Adalimumab
4. Anakinra and Tocilizumab
5. Glucocorticoids

Answer 21

1. Abatacept blocks co-stim of T cells
2. Methotrexate and Leflunomide inhibits the proliferation and activity of T and B cells
3. Etanercept, Infliximab and Adalimumab inactivate TNF-a
4. Anakinra blocks the action of IL-1 and Tocilizumab inactivates IL-6

Question 22

Blocks IL-1 Receptor

Answer 22

Anakinra

Question 23

Inhibits T-cell activation

Answer 23

Abatacept

Question 24

Antibody directed against CD20 antigen on B-lymphocytes

Answer 24

Rituximab