Drug Management of Rheumatoid Arthritis

Question 1

Briefly describe the pathogenesis of rheumatoid arthritis

Answer 1

T lymphocytes reactive to self-antigen activate macrophages and T cells that are reactive to normal tissue.

Results in joint tissue damage.

Question 2

Two different mechanisms of action for disease modifying anti-rheumatic drugs (DMARDs) wtih example drugs.

Answer 2

1. T cell proliferation and function

• Methotrexate
• Leflunomide
• Glucocorticoids

2. Macrophage function

• TNF-α inhibitors
• Glucorticoids

Question 3

How does TNF-α promote inflammation?

Answer 3

TNF-α is secreted by macrophages, acting to activate macrophages themselves, lymphocytes and upregulates adhesion receptors for leukocytes.

Question 4

How do anti-TNF-α antibodies help in RA treatment?

Give two examples of antibodies

Answer 4

Anti-TNF-α antibodes act to suppress inflammation at joints.

Infliximab

Adalimumab

Question 5

Why is it important to humanise antibodies that are given in therapy?

Answer 5

Introducing antibodies = foreign protein to the human, and the immune system would develop antibodies against it, reducing its efficacy.

Humanised Fab sequences minimise human antigenicity.

Question 6

Adverse effects of TNF-α inhibition

Answer 6

• Immune suppression resulting in increased infection rate and increased rate of malignancies
• Risk in people with dormant tuberculosis
• Costly