Approach to Therapeutics

Question 1

What approaches are there in the treatment of inflammatory arthritis?

Answer 1

• Medicines
• Injections
• Therapies
• Surgery

Question 2

What therapeutic categories are there?

Answer 2

• Non steroidal anti inflammatory drugs (NSAID)
• Disease Modifying anti Rheumatic drugs (DMARD)
• Biologics
• Corticosteroids (oral, i-m, i-a)

Question 3

What are disease modifying anti rheumatic drugs?

Answer 3

• A group of structurally unrelated, typically small molecule drugs which have been demonstrated to have slow onset effect on disease activity and retard disease progression.
• Traditionally, these have been associated with identifiable toxicity profiles and risk of occasional serious adverse event.

Question 4

What DMARDs are used in RA?

Answer 4

• Methotrexate
• Sulfasalazine
• Hydroxychloroquine
• Leflunomide

Question 5

What DMARDS are not used in RA any more?

Answer 5

• Gold salts

- Penicillamine

Question 6

What are the general approaches principles for inflammatory joint disease?

Answer 6

• Early and aggressive intervention is the key to obtaining optimal outcomes in the management of RA
• Effective suppression of inflammation will improve symptoms and prevent joint damage and disability

Question 7

What’s so special about methotrexate?

Answer 7

• Effective, well tolerated and cheap
• Cornerstone of combination treatment (with DMARD and biologic)
• People stay on it

Question 8

What treatment strategies can be used for RA?

Answer 8

-Sequential -Monotherapy
-Combination: step up, step down and parallel
Treat to Target

Question 9

What are biologics?

Answer 9

• Biologic DMARDs have been developed from improved understanding of immunology to target key aspects of inflammatory cascade.
• Typically these are large complex proteins which need to be given parenterally.
• Compared to traditional DMARD, they work rapidly, are generally well tolerated although with important toxicities (eg infection and come at high cost.

Question 10

Give examples of biologics currently used?

Answer 10

• TNFa inhibitors (x5)
• IL-1 inhibitors (Anakinra)
• Anti B Cell therapies (CD20, Rituximab)
• Anti T Cell therapies (Abatacept)
• IL-6 inhibitors (Tocilizumab)

Question 11

What issues are there with biologics?

Answer 11

• Efficacy: they have an enhanced response when co prescribed with methotrexate
• Toxicity: minor including injection site reactions to infection and ?malignancy
• Cost

Question 12

How are corticosteroids used in RA?

Answer 12

• Corticosteroids can be prescribed by mouth, by i-a or i-m injection and by i-v infusion
• Short term benefit v long term toxicity
• Rarely appropriate as single drug therapy