Rheumatoid Arthritis Treatments

Question 1

Name the 3 categories of rheumatoid arthritis therapies.

Answer 1

NSAIDs, DMARDs (disease-modifying anti-rheumatic drugs), and biologic response modifiers

Question 2

Indomethacin, naproxen, celecoxib, and other NSAIDs can be used to treat what 2 symptoms of rheumatoid arthritis and acute gouty arthritis? What aspect of these diseases do they not treat?

Answer 2

Treat pain and inflammation; do not slow disease progression

Question 3

Why are the COX-2 selective NSAIDs becoming a more popular treatment for rheumatoid arthritis than the non-selective NSAIDs?

Answer 3

50% less side effects of gastric and duodenal ulcers

Question 4

Name 6 DMARDs (disease-modifying anti-rheumatic drugs) that can be used to treat rheumatoid arthritis.

Answer 4

Gold salts, quinolones, glucocorticoids/corticosteroids, sulfasalazine, methotrexate, and leflunomide

Question 5

Which DMARD is antipruritic and represses macrophage function, but is rarely used today because it causes serious side effects in 30% of patients?

Answer 5

Gold salts

Question 6

The quinolones are both anti-malarials and rheumatic disorder DMARDs. By what mechanisms do they achieve these 2 separate therapeutic functions?

Answer 6

Antimalarial: accumulates in the food vacuoles of Plasmodium and cause oxidative damage

DMARD: reduce T-cell activation and chemotaxis

Question 7

Give one reason a patient would be prescribed a quinolone for rheumatoid arthritis, and one possible side effect if chloroquine was the quinolone prescribed.

Answer 7

Quinolones can be used if the patient is no longer responding to NSAIDs [or can’t tolerate gold or penillamine]; possible side effect is retinal damage

Question 8

What DMARD class can, like NSAIDs, be used to treat both rheumatoid arthritis and acute gouty arthritis? What 2 pathways does this DMARD target?

Answer 8

Corticosteroids/glucocorticoids; inhibits phospholipase A2 (which makes arachidonic acid) and cytokine production (which induces COX-2) pathways

Question 9

By what mechanism does the DMARD sulfasalazine help treat rheumatoid arthritis?

Answer 9

Inhibit TNF-α and IL-1 release

Question 10

Name the 2 immunosuppressive DMARDs. Which one inhibits aminoimidazolecarboxamide (AICAR) transformylase, thymidylate synthetase, and PMN chemotaxis while increasing adenosine accumulation (which is anti-inflammatory)?

Answer 10

Methotrexate and leflunomide; methotrexate has all these actions (note: DHFR inhibition is not seen at these low doses)

Question 11

Which DMARD acts by inhibiting dihydroorotate dehydrogenase (DHODH)? What molecules are not synthesized and what cells’ response to stimuli are inhibited as a result?

Answer 11

Leflunomide; inhibits de novo pyrimidine (UMP) synthesis which inhibits T-cell response to stimuli

Question 12

Which of the following DMARDs is fastest acting: corticosteroids, sulfasalazine, methotrexate, or leflunomide?

Answer 12

Corticosteroids (sulfasalazine takes about 1 month and methotrexate & leflunomide both take several weeks to have an effect)

Question 13

Which DMARD can cause Cushing syndrome-like symptoms as a side effect?

Answer 13

Corticosteroids/glucocorticoids

Question 14

Which class of DMARDs can cause GI problems like nausea, stomatitis, and diarrhea, and also liver problems?

Answer 14

The immunosuppressives (methotrexate and leflunomide)

Question 15

30% of patients discontinue use of which DMARD because of nausea, vomiting, skin rashes, neutropenia, and headaches?

Answer 15

Sulfasalazine

Question 16

List 5 different suppressive strategies employed by biologic response modifiers to treat rheumatoid arthritis.

Answer 16

Block TNF-α, block IL-1, block IL-6, reduce CD20 B cells (using antibodies), and reduce T cells (decrease activation and increase apoptosis)

Question 17

Name the 5 TNF-α antagonists that are used to treat rheumatoid arthritis.

Answer 17

Etanercept, infliximab, adalimumab, golimumab, cirtolizumab

Question 18

Of the 4 monoclonal antibody TNF-α antagonists, which one is a chimeric mouse/human hybrid that can cause an antigenic response in patients? Which one is humanized, and which 2 are fully human antibodies?

Answer 18

Infliximab is chimeric; certolizumab is humanized; adalimumab and golimumab are fully human

Question 19

List the following TNF-α antagonists in terms of how often they are given, from most frequent to least frequent dosing: etanercept, golimumab, adalimumb.

Answer 19

Etanercept (2x/week), adalimumab (2x/month), golimumab (1x/month)

Question 20

Which 4 biologic response modifiers are not TNF-α antagonists?

Answer 20

Anakinra, tocilizumab, rituximab, abatacept

Question 21

Name the biologic response modifier that is an IL-1 antagonist. What is its half life?

Answer 21

Anakinra; 6 hours (short, so need high doses daily)

Question 22

Name the biologic response modifier that is an IL-6 antagonist.

Answer 22

Tocilizumab

Question 23

Name the biologic response modifier that is an anti-CD20 monoclonal antibody. What cells does it target?

Answer 23

Rituximab; B-cells

Question 24

Name the biologic response modifier that inhibits T cell activation and induces T cell apoptosis.

Answer 24

Abatacept

Question 25

What is the most common risk of using TNF-α antagonists or any of the other biologic-response-modifying drugs for rheumatoid arthritis?

Answer 25

Increased risk of serious infections, such as TB, fungal, and other opportunistic pathogens

Question 26

Of the co-stimulation modulators rituximab and abatacept, which one can cause headaches and which can cause hypersensitivity reactions?

Answer 26

Abatacept can cause headaches, rituximab can cause hypersensitivity

Question 27

In current therapy, what drugs are given to patients with early rheumatoid arthritis and low disease activity?

Answer 27

Nonbiologic DMARD monotherapy (ex. hydroxychloroquine, sulfasalazine, methotrexate, or leflunomide)

Question 28

In current therapy, what drugs are given to patients with moderate or high rheumatoid arthritis disease activity but without poor prognostic features?

Answer 28

DMARD monotherapy or the DMARD combination of methotrexate+hydroxychloroquine

Question 29

In current therapy, what drugs are given to patients with moderate or high rheumatoid arthritis disease activity and poor prognostic features?

Answer 29

DMARD combination therapy (ex. MTX+hydroxychloroquine, MTX+sulfasalazine, MTX+sulfa+hydroxy) or anti-TNF therapy

Question 30

In current therapy, what 2 drugs can be given to patients who have rheumatoid arthritis refractory to methotrexate and TNF-α inhibitors?

Answer 30

Rituximab and abatacept