Rheumatoid Arthritis management Flashcards
What are some signs or symptoms of inflamed joints?
Pain, heat, swelling, redness, morning stiffness, loss of function
What is RA
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
What are the general aims of rheumatology treatment?
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
What are extra-articular manifestations?
Painless small lumps under the skin (Rheumatoid nodules) - affects 20%
Also, tiny black patches or spots especially around finger nails (Vasculitis)
How can RA affect other parts of the body?
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
How is RA managed?
Multi-disciplinary education (physio, OT, nurses, doctors)
Joint protection and maintenance
Pain control
Suppression of disease activity
Supervision of disease control
Provision for disabilities
What medications are used for RA management?
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
What are cDMARDs?
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)
What is Methotrexate?
Side effects?
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
What can methotrexate be taken in combination with?
Sulfasalazine, Leflunomide, Hydroxychloroquine, Glucocorticoids
What do Glucocorticoids do?
Examples?
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
What does Sulfasalazine do?
Inhibits the formation of prostaglandins
With or without food
What does Leflunomide do?
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
What does Hydroxychloroquinone do?
An anti-malarial drug that has an immune suppressant effect to decrease immune activity.
With or without food, take with milk if nausea present
What are some side effects of Glucocorticoids
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
How was gold used for RA?
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
What are the second-line agents for RA?
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
What is TNF-a?
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
What is the role of TNF-a in RA?
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
What is Infliximab?
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
What is Entercept?
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)
How effective is anti-TNFa therapy?
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)
Summarise RA treatments
- 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
What are the dietary recommendations for RA?
- 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
