Rheumatoid Arthritis

Question 1

What effect have DMARDs been shown to have in RA?

Answer 1

Slow course of disease
Induce remission
Prevent further destruction of joints and involved tissues

Question 2

What treatment should be given when a patient is diagnosed with RA?

Answer 2

Initiation of DMARDs within 3 months, in addition to NSAIDs, low-dose corticosteroids, physical therapy, and occupational therapy

Question 3

Why is therapy with DMARDs initiated rapidly in RA?

Answer 3

To stop the progression of the disease at earlier stage

Question 4

Is methotrexate used alone or in combination therapy in rheumatoid arthritis?

Answer 4

Either

Question 5

What kind of arthritis is methotrexate the mainstay treatment in?

Answer 5

Rheumatoid or psoriatic

Question 6

What is the effect of methotrexate on the radiograph?

Answer 6

It slows the appearance of new erosions with involved joints

Question 7

When does response to methotrexate occur?

Answer 7

Within 3 to 6 months of starting treatment

Question 8

What kind of drug is methotrexate?

Answer 8

Immunosuppressant

Question 9

What can be done when there is a partial or no response to methotrexate?

Answer 9

Other DMARDs can be added

Question 10

How are the adverse effects of methotrexate minimised?

Answer 10

The doses required for treatment are much lower, and given once a week

Question 11

What are the most common side effects of methotrexate therapy in the treatment of RA?

Answer 11

Mucosal ulceration and nausea

Question 12

What side effects might be seen with chronic administration of methotrexate in RA?

Answer 12

Cytopenias, particularly depression of WBC count, cirrhosis of the liver, and acute pneumonia-like syndrome

Question 13

What monitoring is required with methotrexate?

Answer 13

Signs of infection
Complete blood count
Liver enzyme tests

Question 14

What are the serious side effects of methotrexate?

Answer 14

Mucositis 
Bone marrow suppression
Hepatitis
Cirrhosis
Infection risk
Teratogenic abortifactant

Question 15

What is the oral bioavailability of methotrexate?

Answer 15

Very variable dependant on dose, but when given IV, about 50%

Question 16

What is the half life of methotrexate?

Answer 16

Dependant on dose, but in high doses, about 8-10 hours

Question 17

How is methotrexate metabolised?

Answer 17

Undergoes intracellular/hepatic metabolism to polyglutamates

Question 18

How is methotrexate eliminated?

Answer 18

90% renal, through glomerular active and tubular secretion

Question 19

What therapeutic DDIs does methotrexate have?

Answer 19

Other immunosuppressants, anti-cancer drugs, and in auto-immune conditions

Question 20

What adverse DDIs does methotrexate have?

Answer 20

Drugs affecting renal blood flow, renal elimination, and drugs affecting plasma protein binding, phenytoin, tetracyclines, pencillin.
In combination with these, increased risk of myelosupression

Question 21

What is sulfasalazine made up of?

Answer 21

5-aminosalicylate and sulfapyridine

Question 22

Describe the absorption of sulfasalazine

Answer 22

It has unique pharmacokinetics in the gut, and travels through the length of the upper GI tract until it reaches the colon. Then, in the colon, bacterialaction causes the breakdown of sulfasalazine into 5-ASA and sulfapyridine.

Question 23

What is the mechanism of action of sulfasalazine in RA?

Answer 23

Unclear, not to do with COX-2 inhibition.
Appears to inhibit T-cell proliferation and IL-2 production, and may cause T-cell apoptosis. In neutrophils, it reduces chemotaxis and degranulation

Question 24

What component of sulfasalazine causes ADRs?

Answer 24

Sulfapyridine

Question 25

What % of patients on sulfapyridine (sulfasalazine) experience ADRs?

Answer 25

10-45%

Question 26

What are the common ADRs of sulfapyridine (sulfasalazine)?

Answer 26

Nausea, fatigue, headache

Question 27

What are the serious ADRs of sulfapyridine (sulfasalazine)?

Answer 27

Myelosuppression, hepatitis, allergic rash

Question 28

Is sulfasalazine safe in pregnancy?

Answer 28

Yes

Question 29

What are the DDIs with sulfasalazine

Answer 29

Few

Question 30

What is the onset of action of sulfasalazine treatment in RA?

Answer 30

1-3 months

Question 31

What are IL-1 and TNF-alpha?

Answer 31

Pro-inflammatory cytokines involved in the pathogenesis of RA

Question 32

What secretes IL-1 and TNF-alpha?

Answer 32

Synovial macrophages

Question 33

What happens when synovial macrophages secrete IL-1 and TNF-alpha?

Answer 33

It stimulates synovial cells to proliferate and synthesise collagenase, thereby degrading cartilage, stimulating bone reabsorption, and inhibiting proteoglycan synthesis

Question 34

What effect do TNF-alpha inhibitors have on RA?

Answer 34

Shown to decrease signs and symptoms of RA, reduce progression of structural damage, and improve physical function

Question 35

What is the onset of response with TNF-alpha inhibitors in RA?

Answer 35

Within 2 weeks

Question 36

What are patients receiving TNF-alpha inhibitors at increased risk of?

Answer 36

Tuberculosis, sepsis, fungal opportunistic infections, pancytopenia

Question 37

What rare but serious ADRs can occur with TNF-alpha inhibitors?

Answer 37

Demyelinating disorders and bone marrow suppression

Question 38

What conditions should TNF-alpha inhibitors be caused cautiously with?

Answer 38

Heart failure

Question 39

Why should TNF-alpha inhibitors be caused cautiously with heart failure?

Answer 39

Because they can cause or worsen pre-existing heart failure

Question 40

Give 3 examples of TNF-alpha inhibitors

Answer 40

Infliximab, adalimumab, rituximab

Question 41

What is the mechanism of action of infliximab?

Answer 41

It is a monoclonal antibody that binds specifically to human TNF-alpha, and inhibits binding with its receptors

Question 42

Where is infliximab approved for use?

Answer 42

Patients with RA who have had inadequate response to methotrexate monotherapy

Question 43

How is infliximab administered?

Answer 43

It is infused IV over at least 2 hours

Question 44

What is the half life of infliximab?

Answer 44

9.5 days

Question 45

What are the adverse effects of infliximab

Answer 45

Infusion site reactions, e.g. fever, chills, pruritus, and utricaria Infections leading to pneumonia, cellulitis, and other conditions Leukopenia, neutropenia, thrombocytopenia, and pancytopenia

Question 46

What is the mechanism of action of adalimumab?

Answer 46

A recombinant monoclonal antibody that binds to TNF-alpha, thereby interfering with endogenous TNF-alpha activity by blocking its binding to surface receptors

Question 47

What are the indications for adalimumab?

Answer 47

Severe RA, either as monotherapy or in combination with methotrexate

Question 48

How is adalimumab administered?

Answer 48

Subcutaneously weekly, or every other week

Question 49

What are the adverse effects of adalimumab?

Answer 49

Headache, nausea, agranulocytosis, rash, reaction at injection site, increased risk of infection

Question 50

What is the role of B lymphocytes in RA?

Answer 50

B lymphocytes can perpetuate the inflammatory process in the synvoium by activating T lymphocytes, producing autoantibodies, and producing pro-inflammatory cytokines such as TNF-alpha and IL-1

Question 51

What is the mechanism of action of rituximab in RA?

Answer 51

It is a monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes, resulting in B-cell depletion

Question 52

What is the indication for use of rituximab?

Answer 52

In combination with methotrexate, to reduce signs and symptoms of severe RA in adult patients who have inadequate response to one or more TNF-inhibitors

Question 53

How is rituximab adminstered?

Answer 53

2 IV infusions separated by 2 weeks

Question 54

What are the adverse effects of rituximab?

Answer 54

Infusion reactions are most common