Rheumatoid Arthritis management

Question 1

What are some signs or symptoms of inflamed joints?

Answer 1

Pain, heat, swelling, redness, morning stiffness, loss of function

Question 2

What is RA

Answer 2

A systemic (affects whole body) autoimmune disorder that affects multiple organs.
The immune system chronically over responds and attacks body tissue. Fighting something that isn’t actually there, causes swelling and pain. Causes mass joint inflammation

Question 3

What are the general aims of rheumatology treatment?

Answer 3

Reduce inflammation - & pain, swelling, stiffness and fatigue that comes with it

Protect the body from uncontrolled inflammation damage to joints and bones

Protect another organ that might be affected

Allowing the person to have as normal a life as possible

Question 4

What are extra-articular manifestations?

Answer 4

Painless small lumps under the skin (Rheumatoid nodules) - affects 20%

Also, tiny black patches or spots especially around finger nails (Vasculitis)

Question 5

How can RA affect other parts of the body?

Answer 5

Sjögren’s syndrome - dry eyes and mouth
Anaemia
Carpal tunnel syndrome
Bursitis
Scleromalacia
Leg ulcers
Ankle oedma
Sensorimotor polyneuropathy
Lymphadenopathy
Pericarditis
Tendon sheath swelling
Pleural effusion

Question 6

How is RA managed?

Answer 6

Multi-disciplinary education (physio, OT, nurses, doctors)
Joint protection and maintenance
Pain control
Suppression of disease activity
Supervision of disease control
Provision for disabilities

Question 7

What medications are used for RA management?

Answer 7

Treat-to-target strategy

First line of treatment:
Conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) to control disease progression

• Oral methotrexate
• Leflunomide or Sulfasalazine
• Steroids: Short-term disease/ inflammation suppression

Question 8

What are cDMARDs?

Answer 8

First line agents, alonside NSAIDS
Reduce disease activity and symptoms
Do not have anti-inflammatory to analgesic properties

Slow to take maximum effect (up to 8 weeks)

Question 9

What is Methotrexate?
Side effects?

Answer 9

RA drug
- Taken weekly by tablet or injection, high overdose risk which can be fatal
- Slow in action –> 8-12 weeks

Side effects:
- Chest/ liver/ GI disturbances (B vitamin malabsorption)
- Immunosuppressive effects: risk of infection
- Increased drug interactions

Require chest x-ray and breathing tests before starting use

Question 10

What can methotrexate be taken in combination with?

Answer 10

Sulfasalazine, Leflunomide, Hydroxychloroquine, Glucocorticoids

Question 11

What do Glucocorticoids do?
Examples?

Answer 11

Short term bridging treatment (oral, intramuscular, intra-articular) when starting a new cDMARD.
Bind to glucocorticoid receptors and interrupting the inflammatory cytokine-mediated response
Taken in the morning before breakfast.

Prednisolone, Hydrocortisone

Interfere with gene transcription of mediators of inflammation e.g. COX-2

Question 12

What does Sulfasalazine do?

Answer 12

Inhibits the formation of prostaglandins
With or without food

Question 13

What does Leflunomide do?

Answer 13

Blocks DNA formation, stops cells signally and transcription of new inflammatory proteins made and released
Made specifically for inflammatory arthritis
Has immune suppressant effect

Not recommended in pregnancy
With water, with or without food

Question 14

What does Hydroxychloroquinone do?

Answer 14

An anti-malarial drug that has an immune suppressant effect to decrease immune activity.
With or without food, take with milk if nausea present

Question 15

What are some side effects of Glucocorticoids

Answer 15

Cushing’s syndrome (too much cortisol over a long period of time, leads to fat deposits), growth suppression (protein suppression), osteoporosis (lack of calcium metabolism), decreased healing, suppressed response to infection, increased gluconeogenesis

Question 16

How was gold used for RA?

Answer 16

No longer used
Intramuscular injection
Slow to take effect
Gold salts taken up by macrophages, inhibiting cytokine expression
Bind to proteins and interfere with enzyme substrate receptor-ligand recognition
Reduce oxidative stress

Side effects - skin rash, anaemia

Better more effective drugs now available

Question 17

What are the second-line agents for RA?

Answer 17

Only to be used if at least two cDMARD’s are ineffective, DAS 28 score > 5.1.

Aim to reduce cytokine TNF-a

Etanercept, Infliximab

cept - cytokine inhibitor
mab - monoclonal antibody which inactivates cytokines

Question 18

What is TNF-a?

Answer 18

Tumour Necrosis Factor Alpha
- Potent pro-inflammatory cytokine –> upregulate inflammation
- Product of macrophages (some T cells)
- Dominant stimulant of inflammation
- Induces synovial cell proliferation (Connective tissue around joint, activates cells and secrete other cytokines)
- Synoviocyte activation and proliferation –> induces there secretion of other cytokines

Question 19

What is the role of TNF-a in RA?

Answer 19

Produced by. various immune cells (macropahes, t-cells, synoviocyte)

• Increase other pro-inflammatory cytokines e.g. IL1
• Increased cell migration into joints, e.g. macrophages and neutrophils
• Increased production of enzymes that destroy cartilage

Question 20

What is Infliximab?

Answer 20

Monoclonal antibody against TNF-a, highly specific for TNF-a

IV infusion every 8 weeks
- Patients can self-administer with pre-filled syringes
Half-life 9.8 days

Question 21

What is Entercept?

Answer 21

TNF-a inhibitor, binds to it

Solution for subcutaneous injection
Powder and solvent for solution for injection
Given one or twice weekly
Half-life 70 hours (4.8days)

Question 22

How effective is anti-TNFa therapy?

Answer 22

Pathological impact:
- 30-50% reduction in T-cells
- 40-50% reduction in leucocytes

Clinical impact:
- 50-70% improvement in tender joint count
- 50-70% improvement in swollen joint count
- Improved quality of life
- Reduction in levels of disability
- Arrests joint damage (erosions and joint space narrowing)

Question 23

Summarise RA treatments

Answer 23

• cDMARD monotherapy with oral methotrexate, leflunomide, sulfasalazine, hydroxychloroquine
• Short-term bridging treatment with glucocorticoids
• cDMARDs in combination
• NSAIDs used

Inadequate response:

• Synthetic DMARDS (JAK inhibitors - interfere with cell signalling and protein transcription)
• Biological DMARDS
• Treatment to slow disease progression and lead to remission

Question 24

What are the dietary recommendations for RA?

Answer 24

• Maintain a healthy weight
• Reduce saturated fat, eat more omega-3 and monounsaturated fats
• High-dose fish oil supplements
• Mediterranean diet
• Iron-rich foods, as anaemia can occur as a result of impaired iron absorption during a flare-up
• Calcium-rich foods, especially if using glucocorticoids
• Vitamin D supplements during the winter months