Wk 15: Rheumatoid arthritis: treatment

Question 1

What can be offered for immediate relief of symptoms?

Answer 1

NSAIDs

Question 2

Give examples of traditional DMARDs

Answer 2

• Sulfasalazine

Immunosuppressant:

• Methotrexate
• Leflunomide
• Azathioprine

Antimalarials:

• Hydroxychloroquine

Question 3

Give examples of biological DMARDs

Answer 3

• Rituximab
• Abatacept
• Tofacitinib
• TNF antagonists: Infliximab
• IL6 Inhibitor: Tocilizumab

Question 4

Sulfasalazine (first line) What is the mechanism of action of 5-ASA?

Answer 4

• Inhibit leukocyte movement
• Red cytokine level + TNF
• Inhibit inflammatory mediators: prostaglandins, leukotrienes, platelet activating factors + cyclooxygenase
• Reaches gut before metabolised

Question 5

Methotrexate

Answer 5

• Antifolate: severe RA/intolerant to 1st line
• Blocks pyrimidine/purine biosynthetic pathway
• Blocks the proliferation of B-cells by interfering w/ DNA synthesis, repair + replication

Question 6

Leflunomide

Answer 6

• MOA: metabolise teriflunomide
• Inhibits pyrimidine biosynthetic pathway
• Inhibit DHODH
• Result: dec DNA + RNA nitrogen-containing base + arrest B + T cell proliferation cycles + antibody production

Question 7

Hydroxychloroquine sulfate

Answer 7

• Accumulate + stabilizes lysosomes, impacts antigen presentation = T cell suppression
• In APC, interferes w/ TLR7 + TLR9 ligand binding + LTR signalling -> inhibits TLR mediated cell activation + cytokine prod

Question 8

Adalimumab + Golimumab

Answer 8

Fully humanised monoclonal antibodies specific for TNFa

Question 9

Certolizumab

Answer 9

Fab fragment of humanised monoclonal antibody specific for TNFa

Question 10

Etanercept

Answer 10

Fusion protein consisting of recombinant soluble extracellular portions human TNFR2 + constant domain of human immunoglobulin

Question 11

Infliximab

Answer 11

Chimaeric monoclonal antibody w/ variable region (neutralises TNFa), spliced to constant region of human antibody

Question 12

Anakinra

Answer 12

• Competitively inhibits IL-1 by binding to IL-1 type I receptor
• IL-1 mediates inflammatory + immunological responses

Question 13

Tocilizumab

Answer 13

• Competitive antagonist at IL-6 receptor

- IL-6 = proinflammatory cytokine

Question 14

Abatacept

Answer 14

• Selectively binds to CD80/86 + blocks co-stimulatory signal
• IV infusion

Question 15

Rituximab

Answer 15

• Depletes CD20 by binding to CD20 antigen on cell surface
• Leads to B cell death via apoptosis + lysis
• Used in lymphoma cancer