DMARDs and Immunomodulators

Question 1

DMARDs - Clinical use

Answer 1

Rheumatoid arthritis – limited use (resistance to drug within 5 years, adverse effects)

Question 2

Glucocorticoid

Answer 2

Prednisone

Question 3

Prednisone - MoA

Answer 3

Induce formation of lipocortin which inhibits phospholipase A2, This inhibits release of arachidonic acid. Also inhibit production of cytokines (ILs, TNF)

Question 4

Prednisone - Clinical use

Answer 4

RA to induce remission while waiting for slower-acting DMARD to work.
Short courses during flare-ups. Continuous low-dose background therapy

Question 5

Methotrexate - Classification

Answer 5

Antineoplastic and immunomodulating drug

Question 6

Methotrexate - MoA

Answer 6

Inhibition of human folate reductase which decreases thymidylate and DNA synthesis.

Inhibition of lymphocyte proliferation and production of cytokines and rheumatoid factor.

Interferes with polymorphonuclear leukocyte chemotaxis, which reduces cytotoxins and free radicals

Question 7

Methotrexate - Clinical use

Answer 7

DMARD of choice in most patients with RA

Question 8

Methotrexate - Contraindications

Answer 8

Pregnancy and in combination with leflunomide because of hepatotoxicity

Question 9

Methotrexate - Adverse effects

Answer 9

GI, hematologic, hepatic, pulmonary reactions.

Elevated liver enzymes.

Question 10

Leflunomide - Classification

Answer 10

Immunosuppressive drug

Question 11

Leflunomide - MoA

Answer 11

Inhibits leukocyte and T-cell proliferation by inhibiting pyrimidine synthesis (DNA replication, RNA synthesis, protein synthesis) in immune cells

Question 12

Leflunomide - Clinical use

Answer 12

Alternative to methotrexate for RA

Question 13

Leflunomide - Contraindications

Answer 13

Pregnancy and in combination with methotrexate because of hepatotoxicity

Question 14

Leflunomide - Adverse effects

Answer 14

Diarrhea Reversible alopecia (baldness)
Increased serum hepatic enzymes
Teratogenic

Question 15

Leflunomide - Interactions

Answer 15

Inhibition of CYP2C9: increases serum levels of many drugs (ibuprofen)

Question 16

Hydroxychloroquine - Classification

Answer 16

Antimalarial drug

Question 17

Hydroxychloroquine - MoA

Answer 17

Reduces chemotaxis and phagocytosis of PMNs, reduced superoxides from these cells

Question 18

Hydroxychloroquine - Adverse effects

Answer 18

Blurred vision, scotomas, night blindness

Question 19

Anti TNF-α agents

Answer 19

Etanercept 
Infliximab 
Adalimumab 
Cetrolizumab 
Golimumab

Question 20

Anti TNF-α agents - MoA

Answer 20

Binds to and inactivates TNF-α. Newer agents prevents interleukin binding and T-cell activation.

Question 21

Anti TNF-α agents - Adverse effects

Answer 21

Serious infections and sepsis
Tuberculosis and invasive opportunistic fungal infections
Lymphoma

Question 22

Etanercept - MoA

Answer 22

Dimer of human TNF receptor fused to IgG constant region

Question 23

Etanercept - Clinical use

Answer 23

RA resistant to other DMARDs

Question 24

Etanercept can be combined with

Answer 24

Methotrexate

Question 25

Etanercept - Adverse effects

Answer 25

Injection site reactions

Question 26

Infliximab - MoA

Answer 26

MAb binds to TNF-α and prevents it from activating TNF-α receptor

Question 27

Infliximab - Clinical use

Answer 27

Crohn's disease and rheumatoid arthritis | ankylosing spondylitis, psoriatic arthritis* *=Katzung

Question 28

Infliximab can be combined with

Answer 28

Methotrexate

Question 29

Infliximab - Adverse effects

Answer 29

Hypersensitivity reactions Infection Malignancy Reactivation of latent TB

Question 30

Adalimumab - MoA

Answer 30

Human IgG1 MAb similar to daclizumab, specific for human TNF α

Question 31

Cetrolizumab - MoA

Answer 31

Pegylated Mab directed against TNF α.

Question 32

Golimumab - MoA

Answer 32

Human Mab that binds to both the soluble and transmembrane forms of human TNFα. This interaction prevents the binding of TNFα to its receptor, thereby inhibiting the biologic activity of TNFα.

Question 33

Cytokine inhibitors

Answer 33

Anakinra Canakinumab Rilonacept

Question 34

Anakinra - MoA

Answer 34

Recombinant form of the human interleukin- 1 receptor antagonist (IL-1Ra). Blocks the biologic activity of IL-1 by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI).

Question 35

Anakinra - Clinical use

Answer 35

RA, Gout

Question 36

Canakinumab - MoA

Answer 36

Recombinant human anti-IL-1β monoclonal antibody. It binds to human IL-1β and prevents it from binding to IL-1 receptors.

Question 37

Rilonacept - MoA

Answer 37

Dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP) fused to the Fc portion of human IgG1.

Question 38

Abatacept - MoA

Answer 38

Selective costimulation modulator, inhibits T-cell activation by binding to cell surface markers (proteins) in leukocytes.

Question 39

Abatacept - Clinical use

Answer 39

RA, Sjögren, Psoriasis

Question 40

Tocilizumab - MoA

Answer 40

Humanized anti-IL-6 receptor Mab. Binds selectively to IL-6 receptors and blocks IL-6 acitivity.

Question 41

Tocilizumab - Clinical use

Answer 41

RA | Active systemic juvenile idiopathic arthritis in patients 2 y and older

Question 42

Sulfasalazine - Clinical use

Answer 42

RA

Question 43

Sulfasalazine - Contraindication

Answer 43

Sulfa-allergy

Question 44

D-Penicillamine - MoA

Answer 44

Reduces blood levels of inflammation cytokines

Question 45

D-Penicillamine - Clinical use

Answer 45

RA Less used, better alternatives today. | Copper chelating agent in Willsons disease

Question 46

Apremilast - MoA

Answer 46

Inhibitor of phosphodiesterase type 4 (PDE4) --> increases cAMP levels, which decreases expression of TNFα and other proinflammatory cytokines.

Question 47

Which cytokine inhibitor has the same adverse effects as the TNFα blockers?

Answer 47

Anakinra

Question 48

Aldesleukin - MoA

Answer 48

Recombinant interleukin-2

Question 49

Aldesleukin - Clinical use

Answer 49

Adjunctive treatment of renal cell carcinoma and malignant melanoma.

Question 50

Daclizumab - MoA

Answer 50

Highly specific MAb that binds to the alpha subunit of the IL-2 receptor displayed on the surface of T cells and prevents activation by IL-2

Question 51

Daclizumab - Clinical use

Answer 51

Prevent renal transplant rejection. In comb with other immunosuppressants

Question 52

Interferon–α-2a - MoA

Answer 52

Inhibits cell proliferation

Question 53

Interferon–α-2a - Clinical use

Answer 53

Hairy cell leukemia, chronic myelogenous leukemia, malignant melanoma, Kaposi’s sarcoma, Hepatitis B and C.

Question 54

Interferon-b-1b - Clinical use

Answer 54

Relapsing multiple sclerosis

Question 55

Interferon-g-1b - MoA

Answer 55

Greater immune-enhancing actions. Act by increasing the synthesis of TNF.

Question 56

Interferon-g-1b - Clinical use

Answer 56

Recombinant form: decrease the incidence and severity of infections in patient with chronic granulomatous disease

Question 57

Canakinumab - Clinical use

Answer 57

Gout, Systemic juvenile arthritis

Question 58

Rilonacept - Clinical use

Answer 58

Gout, RA

Question 59

Sulfasalazine - MoA

Answer 59

Suppress T cell response to concanavalin, inhibit B-cell proliferation, and release of inflammatory cytokines.