Clinical Aspects of RA and Approach to Therapeutics Flashcards
What is rheumatoid arthritis?
- A chronic autoimmune systemic illness characterised by a symmetrical peripheral arthritis and other systemic features
- It is one of the commonest chronic illnesses and may be associated with joint damage, disability and premature mortality
What are the 7 RA classification criteria?
- Morning stiffness
- Arthritis of 3 or more joint areas
- Arthritis of hand joints
- Symmetric arthritis
- Rheumatoid nodules
- Serum rheumatoid factor
- Radiographic changes
SAVED UNDER RA CLASSIFICATION 1 and 2
What is the epidemiology of RA?
- 1% pop.
- F:M 3:1
- Peak onset 40s-50s but can occur at any age >16
Describe the genetic aetiology of RA
- Overall incidence of RA ~1% rises to 2-4% in siblings and 12-15% in monozygotic twins
- Genetic contribution to RA estimated to be ~50-60%
- Closest association with specific amino acid sequences at positions 70-74 of DRb1 (shared epitope)
What are the 2 environmental aetiological factors for RA?
- Cigarette smoking
* Chronic infection e.g. periodontal disease
Describe the pathogenesis of RA
Synovitis
SAVED UNDER SYNOVITIS
What immunological investigations are used to diagnose RA?
- Rheumatoid factor (IgG, IgM)
* Anti Cyclic Citrullinated Antibodies (anti CCP, ACPA)
What imaging investigations can be used to diagnose RA?
- X-ray
* MRI
What are the symptoms of arthritis?
- Pain
- Stiffness
- Immobility
- Poor function
- Systemic Symptoms
What are the clinical signs of arthritis?
- Swelling
- Tenderness
- Limitation of Movement
- (Redness)
- (Heat)
What are some non-specific systemic features of RA?
- Fatigue/lassitude
- Weight loss
- Anaemia
What are some specific systemic features of RA?
- Eyes
- Lungs
- Nerves
- Skin
- Kidneys
What are some long-term systemic features of RA?
- CVS
* Malignancy
What are some long-term systemic features of RA?
- CVS
* Malignancy
What score is used to assess RA?
- Disease Activity Score
- DAS<2.4 represents clinical remission
- DAS>5.1 represents eligibility for biologic therapy
What is the outcome of RA?
HISTORIC
•50% of patients dead or disabled within 20 years of diagnosis (1987)
•50% out of workplace within 2 years of diagnosis
•Life expectancy shortened by approx 7 years
2009
•75% of cases diagnosed during working life
•Approx 33% will have stopped working within 2 years
•Approx 50% will be unable to work due to disability within 10 years of diagnosis
•A person with RA will have, on average 40 days sick leave/year (compared with 6.5)
What the treatments inflammatory arthritis?
- Medicines
- Injections
- Therapies
- Surgery
What are the 4 therapeutic categories used to treat RA?
1) Non steroidal anti inflammatory drugs (NSAID)
2) Disease Modifying anti Rheumatic drugs (DMARD)
3) Biologics
4) Corticosteroids (oral, i-m, i-a)
What are Disease Modifying Anti Rheumatic Drugs (DMARD)?
- 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
What are the DMARDs in use?
- METHOTREXATE
- Sulfasalazine
- Hydroxychloroquine
- Leflunomide
What are the DMARDs are no longer in use?
- Gold salts (i-m, oral)
- Penicillamine - toxic
- Others
What is the approach to management of RA?
- 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
- How early and how aggressive
- Move from sequential monotherapy to combination (step up, step down and parallel)
What is so special about methotrexate?
- Effective, well tolerated (severe toxicity is rare) and cheap
- Cornerstone of combination treatment (with DMARD and biologic)
- People stay on it
How are biologics used in arthritis?
- 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 and are generally well tolerated although with important toxicities e.g. infection and come at high cost
Which biologics are used to treat RA?
- TNFa inhibitors (x5)
- IL-1 inhibitors (Anakinra)
- Anti B Cell therapies (CD20, Rituximab)
- Anti T Cell therapies (Abatacept)
- IL-6 inhibitors (Tocilizumab, Sarilumab)
- Oral kinase inhibitors (JAK inhibitors) (Baricitinib, Tofacitinib)
How do DMARDs compare with biologic DMARDs?
- They are much less complicated molecules
* Biologics much be given parenterally
What are the issues with biologics?
- Efficacy - enhanced response when used with methotrexate
- Toxicity - Minor (e.g. injection site reaction), infection, ?malignancy
- Cost - £9500 vs. £50
How can corticosteroids be administered?
- By mouth
- IA (intra-articular) or IM injection
- IV infusion
What are the issues with using corticosteroids?
- Short term benefits vs. long term toxicity
* Rarely appropriate as single drug therapy
What blood test results may indicate RA?
- Raised CRP and ESR
- Positive RF
- Positive anti CCP (cyclic citrullinated peptide) antibody
How might you initiate RA treatment?
•Corticosteroids and a DMARD
can be moved up to dual DMARD therapy
How do you keep monitoring RA?
- DAS28
- Monthly appointment
- Monitoring blood tests
Describe the MDT for early RA
- Rheumatology Specialist Nurse
- Rheumatology Occupational Therapist
- Rheumatology Physiotherapist
- Pharmacist
- Clinical Psychologist
- Podiatrist
- Orthotics
How might you assess a patient for treatment escalation to biologic therapy?
- BCG scar/chest x-ray
- Chronic infection screening - hep B and C, quantiferon test (for TB)
- Varicella-zoster serology - biologic therapy would increase immunosuppression
What are the risks of corticosteroid use?
- CVS
- T2DM
- Osteoporosis
What are the complications of RA?
•Orthopaedic intervention -Chronic synovitis -Mechanical deformities -Secondary osteoarthritis -Poor function -Pain •Extra-articular involvement -Rheumatoid nodules -Interstitial lung disease -Vasculitis •Cardiovascular risk •Socio-economic
How can functional impairment caused by RA be combated?
- Special adaptive cutlery
- Special footwear
- Walking aids
- Use of wheelchair for outdoors
- Supportive family
- Care package
