Disease Modifying Anti-RA Drugs (Wolff)

Question 1

What are the 4 csDMARDS (non-biologics)

Answer 1

1. methotrexate (drug of choice for RA)
2. hydroxychloroquine (lysosomal pH)
3. sulfasalazine (sulfa drug and “triple therapy)
4. leflunomide (second drug of choice for RA)

Question 2

What are the 5 categories of bDMARDS (biologics)

Answer 2

1. TNF alpha blockers (etanercept, adalimumab, infliximab)
2. B cell depleted (CD20 mAb) (rituximab)
3. T cell activation inhibitor (abatacept)
4. IL-6 receptor mAb (tocilizumab)
5. Recombinant IL-1 antagonist (anakinra)

Question 3

What is the one tsDMARD?

Answer 3

jak 3 inhibitor - tofacitinib

Question 4

methotrexate

Answer 4

csDMARDS (non-biologics); inhibitor of DHF reductase; works faster than all other DMARDs (3-6 weeks) and works in 80% of patients; drug of choice for RA; taken once per week orally or by injection; well tolerated but can have life threatening toxicities of bone marrow suppression; contraindicated in pregnancy (fetal death)

Question 5

What is the faster working DMARD?

Answer 5

methotrexate; csDMARDS (non-biologics); inhibitor of DHF reductase

Question 6

What is the drug of choice for RA?

Answer 6

methotrexate; csDMARDS (non-biologics); inhibitor of DHF reductase

Question 7

hydroxychloroquine (HCQ)

Answer 7

a csDMARDS (non-biologics); weak base that accumulates in lysosomes; increased the pH and limits the class II MHC presentation on immune cells; also an antimalarial drugs; toxicity of IRREVERSIBLE retinal damage

Question 8

Which drug works by increases the pH in lysosomes?

Answer 8

hydroxychloroquine (HCQ); increased the pH and limits the class II MHC presentation on immune cells

Question 9

Which drug is there a risk for IRREVERSIBLE retinal damage?

Answer 9

hydroxychloroquine (HCQ); increased the pH and limits the class II MHC presentation on immune cells

Question 10

sulfasalazine

Answer 10

a csDMARDS (non-biologics) used to treat RA in a “triple therapy” with methotrexate and hydroxychloroquine (HCQ); GI side effects also a sulfa drug

Question 11

leflunomide

Answer 11

a csDMARDS (non-biologics) used to treat RA; inhibits T cell proliferation; second drug of choice in RA; can cause hepatotoxicity and increase the risk of serous infections

Question 12

treatment recommendation for patients with LOW disease activity?

Answer 12

csDMARDS (non-biologics)
hydroxychloroquine (HCQ) > sulfasalazine > methotrexate > leflunomide

Question 13

general rules regarding biologic DMARDs?

Answer 13

1. they have a faster onset of action than the non-biologics
2. they have a high rate of response
3. they are more expensive
4. they have increased risks for severe adverse effects

Question 14

What are the 3 TNF alpha blockers?

Answer 14

work by neutralizing TNF, risk of serious infections, TB and allergic reactions

etanercept - fusion protein, once weekly subQ injection (93K/yr)
adalimumab - chimeric mAb, every 8 weeks (16K/yr)
infliximab - recombinant anti-mAb, lowest risk, BEST SELLING DRUG IN THE WORLD (100K/yr)

Question 15

rituximab

Answer 15

a bDMARDS (biologics) B cell depleted (CD20 mAb); “a B cell do over”; used in combination with methotrexate; watch for hypersensitivity reactions

Question 16

abatacept

Answer 16

T cell activation inhibitor bDMARDS (biologics); “blocks the secret handshake between B cells and T cells”; prevents CD28 and CD80/86 binding; not used until after TNF antagonist have failed; risk of serious infections

Question 17

tocilizumab

Answer 17

IL-6 receptor mAb bDMARDS (biologics); competes for human IL-6 receptor; limits hepatic acute phase response and activation of T cells; adverse effects of URI’s and life threatening infections

Question 18

Which drug has an adverse effect of causing URI’s?

Answer 18

tocilizumab; IL-6 receptor mAb bDMARDS (biologics); competes for human IL-6 receptor; limits hepatic acute phase response and activation of T cells; adverse effects of URI’s and life threatening infections

Question 19

anakinra

Answer 19

Recombinant IL-1 antagonist bDMARDS (biologics); blocks the pro-inflammatory effects of IL-1; consider less efficacious and a late choice for RA treatment; risk of serious infections and hypersensitivity reactions

Question 20

tofacitinib

Answer 20

the one tsDMARD; jak 3 inhibitor the directly suppresses the production of IL-17 and IFN-gamma and the proliferation of CD4+ T cells; administered orally; can cause fatal infections and increases risk for malignancies (thought to be overpriced)