Rheumatoid Arthritis

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  • Created by: LBCW0502
  • Created on: 26-01-19 10:24
Give examples of inflammatory arthritis
Rheumatoid arthritis, gout and ankylosing spondylitis (inflammation in spine)
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Give an example of a non-inflammatory arthritis
Osteoarthritis
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Give an example of a connective tissue disease
Systemic lupus erythematosus
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Give an example of a bone disease
Osteoporosis
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What is RA? (1)
Chronic systemic inflammatory disease (autoimmune condition - immune system primarily attacks joints). Causes persistent symmetrical joint synovitis (inflammation of the synovial membrane)
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What is RA? (2)
All lead to a final common pathway - persistent synovial inflammation, damage to articular cartilage, damage to bone. Joints can lose shape and alignment and destroyed completely. Typically affects small joints of hands and feet
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Why is RA important?
People stop working, unable to work due to disability, sick days, reduces life expectancy by 6-10 years in severe RA, 580,000 people affected in England and Wales. Peak onset 40-70 years. F:M, 3:1
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What is RA associated with?
CVD, stoke, infections, osteoporosis, depression, cancer (for pharmacists - drug management + high risk + high cost)
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What are the two types of antibodies in RA?
Rheumatoid Factor (RF) and Anti-Citrulinated Peptide Antibodies (ACPA)
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Describe features of RF
Present in 50% of early RA. Attacks receptors on macrophages. Not very specific or sensitive. More fibrosis than joint destruction. Response to treatment may differ from ACPA
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Describe features of ACPA
More specific and sensitive for RA. Poor prognosis. More aggressive joint destruction. Lower remission rates. Majority of patients ACPA + also RF +
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What are the two types of synoviocytes in the synovial membrane?
Fibroblast-like cells (produce synovial fluid) and macrophage-like cells (fight infection)
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Describe features of a RA joint
Synovial membrane thickened, produce more inflammatory mediators (e.g. B-cell, T-cell, plasma cell, macrophages), more synovial fluid, unknown stimulus (body doesn’t know cause, identification of foreign body)
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What are the inflammatory cytokines in RA?
Tumour necrosis alpha (TNFα), IL-1, IL-6 and IL-17 (pro-inflammatory mediators)
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Describe features of TNFα
Key inflammatory cascade in RA. Drives synovial inflammation and joint destruction. Over production due to interacting T/B lymphocytes, synovial-like fibroblasts and macrophages. Stimulates production of other cytokines (IL-6) causing further damage
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What are the risk factors for RA?
Genetic (HLA-DRB1 allele), smoking (ACPA+, amount and duration, risk remains after cessation). Genetic + smoking (21x increase). Alcohol (decrease), pregnancy (decrease), environmental factors, obesity (pressure on joints)
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What are the common symptoms of RA?
Painful swollen joints, stiffness, fatigue, depression, irritability, anaemia, flu-like symptoms (patients have difficulty taking their medicines)
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What are the less common symptoms of RA?
Weight loss, eye inflammation, rheumatoid nodules, inflammation elsewhere in body
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What are the extra-articular features (experienced by 30% of patients?
CNS (nerve entrapment, peripheral neuropathy). Pulmonary (nodules, effusions, fibrosis). Cutaneous (rashes, ulceration). Ocular (inflammation). Cardiac (inflammation, effusions, valve disease, abnormal conduction). Blood vessels (inflammation)
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What are the signs of RA (blood tests)? (1)
C-reactive protein blood test to identify RA (higher levels, worse infection), CRP should be <1 but for RA patients it can be 100
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What are the signs of RA (blood tests)? (2)
Erythrocyte sedimentation rate – ESR blood test (rate faster, erythrocytes fall down quicker, indicates RA)
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What are the signs of RA (blood tests)? (3)
RF and ACPA (+/-)
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What are the signs of RA (radiographic)?
Erosions shown on X-ray
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Describe features of the ACR/EULAR 2010 Criteria
Scores provided based on joint involvement, serology/RF/anti-CCP, CRP/EDR and duration of symptoms. 6+ indicates defined RA
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Describe features of the DAS28 clinical assessment
A combined index of individual assessments. 28 swollen/28 tender joints (hands, arms, knees). Patients global assessment. ESR/CRP. Score of 3.2+ indicates moderate-high activity, score <2.6 indications remission (aim). NICE defines response as >1.2
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What are the treatment aims? (1)
HCPs. Remission or sustained low disease activity (non-biologic DMARD monotherapy, non-biologic DMARD + non-biologic DMARD, non-biologic DMARDs + biological DMARD IV, glucocorticoids/NSAID for symptom relief during flares)
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What are the treatment aims? (2)
Early management and treatment is key before irreversible destruction of joints
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Describe features of RA management (1)
Short term relief (NSAIDs). Short term disease control (glucocorticoids). Long term disease control (DMARDs - MTX, leflunomide, biologics - TNFα). Surgery (severely deformed joints). Non-drug (exercises, psychology, education)
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Describe features of RA management (2)
Co-morbidities (depression, osteoporosis, CV disease)
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What is the treatment for early RA?
Methotrexate (1st line) - co-prescribed with folic acid 5 mg once a week. + sulfasalzine or leflunomide (2nd line). Other DMARDs (hydroxychloroquine (esp. if mild RA). Remission - stabilise on on DMARD and escalate if needed
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What is the treatment for established RA?
Aim (minimise disease activity). DMARDs + biologic, +/- glucocorticoids/NSAIDs PRN. Persistent disease/flares (switch biologic/DMARD). 1st line biologic (TNF inhibitor - switch if adverse effect, use alternative if anti-TNF not option)
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Describe features of NSAIDs (1)
Effective at reducing pain/stiffness. No effect on underlying disease process. Use lowest effective dose for shortest possible period of time
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Describe features of NSAIDs (2)
Undesirable long term adverse effects (MI/stroke - assess risk factors, GI bleeds - GI protection with PPIs). Drug interactions/co-morbidities, avoid low dose aspirin/warfarin. COX 1/2
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Describe features of glucocorticoids (1)
Reduce synovitis, pain, may improve joint function. Reduce joint damage in long term but - osteoporosis, diabetes, glaucoma, infections. Useful for short-term treatment of flares and allow time for DMARDs to work
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Describe features of glucocorticoids (2)
Local intra-articular injections are highly effective local treatments for active joints
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What is the dosage for methotrexate to treat RA?
7.5 mg - 25 mg once a week (one the same day each week)
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What are the routes of administration for methotrexate?
Oral, subcutaneous, or intramuscular
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What are the adverse effects of methotrexate?
Nausea, vomiting, diarrhoea (consider SC/IM), mouth ulcers, hair loss, rashes, infections, bone marrow suppression, hepatotoxicity, pulmonary fibrosis
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What monitoring is required for methotrexate?
Full blood count, liver function tests, renal function, lung function
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What are the counselling points for methotrexate? (1)
Recognising warning signs/symptoms, dose/frequency (once a week), need blood monitoring and booklet, need adequate contraception, avoid live vaccines (immunosuppressant), alcohol intake (oral cheaper than parenteral)
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What are the counselling points for methotrexate? (2)
Dispense only 2.5 mg tablets, co-prescribe folic acid 5 mg weekly (not on day of methotrexate - MOA)
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Describe features of sulfasazaline to treat RA (1)
0.5 - 2 g daily in divided doses. Oral route. ADRs - nausea, vomiting, abdominal pain, skin rashes, bone marrow suppression, hepatoxicity. Monitoring - FBC, liver function. Counselling - urine colour change (orange), contact lens staining
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Describe features of sulfasazaline to treat RA (2)
Adequate contraception. Cheaper. May effect male fertility (reversible on withdrawal)
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Describe features of leflunomide to treat RA (1)
100 mg daily for 3 days then 10-20 mg daily. Oral route. ADRs - nausea, diarrhoea, mouth ulcers, weight loss, hypertension. Monitoring - FBC, liver function, BP, bone marrow suppression, hepatotoxicity. Expensive
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Describe features of leflunomide to treat RA (2)
Very long half life (complex wash out procedure). (Azathioprine, hydroxychloroquine , rarely use gold/sodium aurothiomalate, pencillamine and cyclosporin)
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Describe features of safe DMARD use
Patients provided with PIL, medicines monitoring record (check blood count). Shared care plan distributed to HCPs to continue patient's treatment
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When should you stop treatment for RA in a patient? (1)
If remission is achieved (combination therapy). Family planning, pregnancy or breast-feeding. ADRs (liver toxicity). Inter-current illnesses (severe infections - methotrexate is an immunosuppressant). Primary failure (never responded)
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When should you stop treatment for RA in a patient? (2)
Secondary failure - responded reducing effect, (not life threatening to miss a dose of methotrexate, symptoms would not flare up)
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Describe features of biologic drugs (1)
Very expensive in UK, restricted by NICE. DAS28 > 5.1 on two separate occasions at least 1 month apart. Patients must have failed or be intolerant of 2 DMARDs (one must be MTX). Usually used in combination with MTX to maximise efficacy
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Describe features of biologic drugs (2)
Difficult to compare agents as trial design differs. Efficacy best demonstrated in patients that have failed or particular response to DMARDs
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Give examples of biologics (1)
TNFα target - Adalimumab (human), Certolizumab Pegol (humanised), Golimumab (human), Infliximab (human/foreign). B cells (CD20) - Rituximab (human/foreign). IL-6 - Tocilizumab (humanised)
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Give examples of biologics (2)
Etanercept is a fusion protein inhibitor – a decoy receptor for TNFα. (Animal source, human sources)
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Describe features of adalimumab (anti-TNF)
(1st line) 2 weekly, SC route, self-administration, costs £8900, half life of 14 days
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Describe features of certolizumab pegol (anti-TNF)
(Pregnant women) 2 weekly, SC route, self-administration, cost £6400, half life of 14 days
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Describe features of etanercept (anti-TNF)
Weekly, SC route, self-administration, cost £9300, half life of 3 days
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Describe features of golimumab (anti-TNF)
Monthly, SC route, self-administration, cost £9100, half-life of 9-15 days
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Describe features of infliximab (anti-TNF)
0, 2, 6 then 8 weekly. IV route, no self-administration, cost £16,600, half life of 8-9.5 days
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Describe features of anti-TNF safety
Injection site reactions, infusion reactions, infections (increased risk of TB, hepatitis B/C reactivation, sepsis, cellulitis, abscesses, UTIs, thrush, herpes, LRTIs), vaccination, cancer (RA pts > risk of lymphoma), CI in heart failure
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When should you stop or switch the anti-TNF?
(NICE) - try for 12-16 weeks to ensure response is seen. Primary failure (within 6 months, cannot use that same drug class e.g. TNF alpha inhibitor) use different biologic. Secondary failure - within 12 months, use another TNF-alpha (body reacting)
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Describe features of rituximab (1)
Chimeric human/mouse mab. Targets CD20 receptor on beta cells (antigen presentation, autoantibody formation, cytokine production). Licensed for use after TNF failure. Dose of 2 x 1 g within 6 months/long t 1/2. (not first line, 2nd/3rd line), PML
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Describe features of rituximab (2)
May only need 3 infusions per year due to long half life
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What is PML? (1)
Progressive multifocal leuko-encaphalopathy - life-threatening condition, caused by reactivation of JC virus (when immune system is suppressed by rituximab, damages brain and spinal cord (found in 70-90% adults)
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What is PML? (2)
Signs and symptoms include - pins/needles, shaky movements, loss of vision, changes in behaviour or mood, difficulty with movements (face/arms/legs), weakness, unsteady on feet, problems with speech
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Describe features of abatacept (1)
Fusion protein inhibitor prevents T-cell activation. Licensed for use after DMARD and anti-TNF failure. NICE guidance after anti-TNF + rituximab failure. IV infusion 0, 2, 4 then every 4 weeks (dose banded weight 500-1000 mg) or 125 mg weekly subcut
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Describe features of abatacept (2)
Less infections, infusion reactions. Cost £12,200 (+£8200 infusion costs)
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Describe features of tocilizumab (1)
Humanised anti-IL 6 receptor antibody. IL-6 activates T/B-cells, macrophages, osteoclasts. Licensed for used after DMARD or anti-TNF failure. NICE guidance (after anti-TNF + rituximab failure). 8mg/kg every 4 weeks IV or weekly subcut 162 mg
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Describe features of tocilizumab (2)
Infections, neutropenia, infusion reactions, diverticulitis, hyperlipidaemia, hepatotoxicity. Cost £11,200 (+£7600 infusion costs). Subcut preparation lower cost
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Describe features of secukinumab (Novartis) (1)
IL-17A inhibitor. SC injection (loading weekly dose for one month then monthly). NICE approved for active psoriatic arthritis and ankylosing spondylitis. PSA anti-TNS non-responders (300 mg, 0, 1, 2, 3, 4, then monthly)
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Describe features of secukinumab (Novartis) (2)
Anti-TNF responders (150 mg 0, 1, 2, 3, 4). AS (150 mg 0, 1, 2, 3, 4 then monthly). Cost £6592-13184 (£8800 infusion cost)
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Describe features of baricitinib (Pfizer)
Janus kinase (JAK) inhibitor. T-cells need JAK for cytokine signalling. Moderate to severe active RA. Oral agent 4 mg OD (2 mg OD, age > 75). Cost £5500
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What are the disease considerations?
Defining disease subsets. Target high cost intensive treatments. Moving from long-term continuous treatment to early aggressive treatment achieving remission then drug withdrawal. Dose reduction and withdrawal for patients currently in remission
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Describe features of biosimilars
Huge saving to NHS (e.g. infliximab, adalimumab). 40% cheaper than current branded products. NICE. Change in first line product? Switch patients? Patient acceptability, clinician acceptability, workload of switching 100s of patients
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What are the roles of the pharmacist? (1)
Clinical guidelines (biologic pathway, shared care). Patient information. Pharmacist led monitoring clinics. Medicines information to rheumatologists. Prescribing/monitoring clinics. Biosimilar switching. Drug expenditure. Business planning
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What are the roles of the pharmacist? (2)
Formulary applications. Individual funding requests (IFR). Unlicensed/off-label use. Audit/research. Education/training. Free of charge and compassionate use
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Osteoarthritis

Card 3

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Give an example of a connective tissue disease

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Card 4

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Give an example of a bone disease

Back

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Card 5

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What is RA? (1)

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