Drugs for RA

Question 1

What is RA?

Answer 1

Causes significant systemic effects
–shorten life and reduce mobility and quality of life
Autoimmune disease driven primarily by activated T cells
–give rise to cytokines like IL-1 and TNF

Question 2

What are the three classes of drugs used for treatment of RA?

Answer 2

NSAIDs (symptomatic relief and inflammation reduction)
Glucocorticoids (relieve joint symptoms and control systemic manifestations)
DMARDs (longer onset of action)
(Neither NSAIDs nor glucocorticoids prevent disease progression or joint destruction)
(DMARDs reduce or prevent joint damage and delay or stop progression of disease)

Question 3

What are the DMARDs prescribed for RA?

Answer 3

Methotrexate: first DMARD prescribed

Biologic DMARDs: TNF alpha inhibitors are for more moderate to severe disease

Question 4

Methotrexate is the first choice to treat RA however what are other Non-biologic DMARDs?

Answer 4

Leflunomide:
–as effective as methotrexate – pt can be given combo therapy with methotrexate if they do not respond to methotrexate as a monotherapy

Question 5

What is the 3rd non-biologic DMARDs?

Answer 5

Hydroxychloroquine: 
---moderately effective for mild RA 
--least toxicity 
--least effective as monotherapy (used with methotrexate and sulfasalazine) 
3-6 months to see effectiveness

Question 6

What is the 4th non-biologic DMARDs?

Answer 6

Sulfasalazine:
Effective for RA
2-3 months to become apparent

Question 7

What is the 5th non-biologic DMARDs?

Answer 7

Cyclosporine

–can be helpful in RA but nephrotoxicity and many interactions with drugs and food is limited

Question 8

What is the 6th non-biologic DMARD?

Answer 8

Azathioprine

–used for patients with refractory RA or systemic involvement (rheumatoid vasculitis)

Question 9

What is the 7th non-biologic DMARD?

Answer 9

Cyclophosphamide
–limited to most severe cases of RA (systemic features)
–long term use increases risk of infection and malignancy
Effective against RA when given orally

Question 10

Moving on to the Biologic DMARDs, these are your Anti-TNF alpha drugs. What are some general features of these drugs?

Answer 10

Adalimumab, Infliximab and Etancercept
Mediated by specific membrane bound TNF receptors
—TNF alpha is particularly important in the inflammatory process
Act much quicker
When used in combo with methotrexate there is synergistic effects

Question 11

What are other options for drugs in RA?

Answer 11

Rituximab:
–given concurrently with methotrexate or another nonbiologic DMARD
Abatacept:
–patients who did not respond to nonbiologic DMARDs or anti-TNF agents
Anakinra
–moder to severe RA

Question 12

Next set of drugs used for RA are glucocorticoids, what are some features?

Answer 12

Relieve joint symptoms and control systemic manifestations
There are many complications so usually these are used until the effects of DMARDs become apparent
Fast acting
Intra-articular injection of corticosteroid can often relieve an acutely inflamed rheumatoid join

Question 13

What are some adverse effects of glucocorticoids?

Answer 13

Osteoporosis
Weight gain 
Fluid retention 
Cataracts 
Poor wound healing 
Gastric Ulcers 
GI bleeding 
Hyperglycemia 
HTN 
Adrenal Suppression 
Increased risk of infection

Question 14

NSAIDS can also be used for RA, when is this appropriate?

Answer 14

Immediate analgesic and anti-inflammatory effects

Bridge drugs for relief of symptoms

Question 15

In regards to RA what are the choice of drugs?

Answer 15

Non-biological DMARD and add an NSAID or corticosteroid to control symptoms
(DMARD = methotrexate)

Question 16

In regards to RA, what is the drug of choice in patients with severe disease?

Answer 16

Combine Biologic DMARD with a non-biologic DMARD (methotrexate) for initial treatment
(Non biologic = TNF alpha inhibitors)

Question 17

Finally just to touch on combination therapy, what are some features?

Answer 17

1. Combination DMARD therapy may be more effective than monotherapy
2. Combination therapy typically includes weekly methotrexate, to which other agents are added
3. Combination of different biological agents increases the risk of infection and is not recommened

Question 18

Leflunomide in combination with methotrexate has what side effect?

Answer 18

Increases risk of hepatotoxicity

–patients need to be monitored closely

Question 19

What combo therapies have been shown to be effective in RA patients?

Answer 19

Methotrexate + hydroxychloroquine
Methotrexate + sulfasalazine 
Methotrexate + hydroxychloroquine + sulfasalazine 
Methotrexate + cyclosporine 
Methotrexate + leflunomide 
Methotrexate + gold 
Methotrexate + TNF inhibitor