Flashcards in Rheumatoid Arthritis Deck (47):
what percentage of people suffer from rheumatoid arthritis?
1 to 3%
is rheumatoid arthritis more common in men or women?
three times more common in women
when does rheumatoid arthritis exhibit peak onset?
what percent of patients are clinically disabled due to aggressive RA and how long does it take for this to occur?
what are the proposed causes of RA
what is the pathophysiology of RA?
Disease of the synovium characterised by:
-infiltration of the synovium by lymphoid cells
-formation of new blood vessels
What are the earliest signs of RA?
Swelling of the synovial membrane and connective tissue.
Effusion of watery synovial fluid into joint space.
what are the late signs of RA?
deformity due to dislocation
what are the clinical presentations of RA?
signs of inflammation: Heat, swelling, function loss
-initially pain on movement
-progression:rest pain + early morning stiffness
-Flare-ups: stiffness all day
List the non-articular manifestations of RA?
-Anaemia: chronic disease, iron deficiency, vitamin B12/folic acid deficiency
-Dry, gritty eyes (sjogren's syndrome)
what are the methods of RA dianosis?
-clinical: ACR/EULAR guidelines
-radiological (x-ray) change
*ESR; normal 2-5mm/hr, RA >50mm/hr
*CRP; normal 0-6mg/L, RA 10mg/L
starting from the bottom list the treatment pyramid for RA
NSAIDS + simple analgesics
When does most damage occur in RA?
First 5 years
When does max disease activity of RA occur?
first 2 years
Explain the current approach to RA therapy
Damage is greatest within first 3-5 years
therefore pyramid is ineffective.
traditional approach is reversed and DMARDs are used for treatment at early stage as:
-early diagnosis means limited inflammation therefore prevention of long term damage
-aggressive therapy used before damage occurs.
Discuss the use of simple analgesics for RA treatment?
often taken with NSAIDs
-paracetamol alone or in combination with: codeine or dihydrocodeine
-can be used when NSAIDs are contraindicated
Discuss the use of NSAIDs for RA treatment?
90% of RA patients receive NSAIDs at some stage
-Anti-inflammatory effect within 1-2 weeks
-taken alone or in combination with analgesics or DMARDs
-Late pm/early am doses to combat early morning stiffness
Discuss the use of corticosteroids for RA treatment?
-rapid relief from inflammatory symptoms
-Inhibit pro-inflammatory response of cytokines
-bridges the gap between initiating DMARDs and clinical response
Discuss the use of Oral prednisilone for RA treatment?
-dose: 5 - 7.5mg daily or 15mg daily if used intermittently
Discuss the use of IV pulse therapy for RA treatment?
-severe refractory disease
-methylprednisolone 1G over 30-45 minutes as a single dose for 3 days
-best use: adjunct to other drugs!
Discuss the use of Intra-articular steroids for RA treatment?
-Joint aspirated and steroid injected aseptically
-large joints: triamcinolone, methylprednisolone
-smaller joints: hydrocortisone
What do DMARDs do in terms of RA treatment?
-Not analgesic agents
-Not DIRECTLY anti-inflammatory
-effective in only RA
-Have joint and non-articular effects
-they lower the ESR + rheumatoid factor titres
-Slows disease progression
Discuss the process of choosing a DMARD?
use determined by toxicity:efficacy ratio
-response and side effects unpredictable (anti-inflammatory MOA unknown)
-Sulfasalazine most frequently used
-followed by methotrexate, gold, penicillamine.
List the order of most frequently used DMARDs
Sulfasalazine, methotrexate, gold, penicillamine
Why is methotrexate so widely used?
1)early onset of action
4)High patient tolerability
5)Used in patients with severe inactivated disease
Discuss methotrexate Dosing?
initial dose 7.5mg per week on same day.
increase in 2.5mg increments
MAX 20mg weekly
Most frequent dose used 15mg weekly
Folic acid co-prescribed (taken 24-48hrs after methotrexate dose)
What are methotrexates Side effects, contraindications and interactions?
-generally mild: 20-30% patients stop treatment
-pre-existing hepatic disease
-Heavy alcohol use or alcoholism
-impaired renal function
-NSAIDs, oral hypoglycaemics, phenytoin
Discuss the use of sulfasalazine for RA treament including side effects and contraindications?
-Clinical response 8-12 weeks
-well-tolerated by 40% of patients long term
*nausea- most common, enteric coated tablets and gradually increase dose.
-Contraindications: previous hepatic disease, pregnancy
Discuss the use of Anti-malarials for RA treament including side effects dosing?
-previous first line therapy
-considered least toxic
-side effects: retinopathy (related to dose)
-no longer commonly used
-occasionally used in combination therapy
-Hydroxychloroquine drug of choice (less ocular toxicity):
200mg bd up to 6 months
decrease to 200mg daily following remission
Discuss the use of GOLD for treatment of RA?
sodium aurothiomolate (IM GOLD)
-when tolerated its most effective
-use limited by side effects
-only use after failure of methotrexate
Auranofin (Oral gold)
-one of the most toxic DMARDs
-40% of patients stop therapy due to incidence of side effects
-Contra-indications: Pregnancy + renal or hepatic disease
Discuss the use of penicillamine and ciclosporin for treatment of RA?
-absorption decreased by 50% in presence of food, antacid and iron supplements
-previously used in patients for whom other treatment had failed
-now used early in disease, particularly in combination with methotrexate.
Discuss the use of Leflunomide for RA treament including side effects, dosing and contra-indications?
Efficacy similar to methotrexate and sulfasalazine
-long t1/2 (15-18 days)
-loading dose 100mg daily for 3 days, then 10-20mg daily
-rapid onset of action- 4 weeks
-skin disorders, diarrhoea, abdominal pain, potential added toxicity when used in combination with other DMARDs.
List the biological therapies used to treat RA
1)TNF alpha inhibitors: infliximab, etanercept, Adalimumab
What do TNF alpha inhibitors do?
Inhibit tumour necrosis factor alpha, a pro inflammatory cytokine.
Discuss the use of Infliximab for treatment of RA?
Profound TNF depletion maintained for weeks!
-licensed for RA and crohns disease
*3mg/kg as IV infusion at 0, 2, 4 and then every 8 weeks
*can increase in steps of 1.5mg/kg every 8 weeks to max 7.5mg/kg every 8 weeks
-methotrexate must be given concomitantly (HACA- human anti-chimeric antibodies)
what are the problems of Infliximab treatment?
more common with long interval between doses, reduced with concurrent methotrexate therapy.
-allergic reactions including anaphylaxis during and up to 2 hours post infusion (hospital adm only)
-infection and malignancy
-severe heart failure
Discuss the use of etanercept in the treatment of RA
-genetically engineered fusion protein (TNF receptor)
-given subcutaneously: 25mg injection twice weekly or 50mg once weekly (self administered)
-Human protein: no HACA problems
-side effects: injection site reactions, RTI or blood disorders
Discuss the use of treatment of Adalimumab (humira) in treatment of RA
-genetically engineered fusion protein (TNF receptor)
40mg injection fortnightly (self administered)
40mg weekly (w/o methotrexate)
onset of action 1-2 weeks)
-human protein: no HACA problems
-side effects:injection site reactions, RTI, blood disorders
What is the NICE guidance on the TNF alpha inhibitors for RA?
-Continuing clinically active RA that has not responded adequately to at least 2 DMARDs
-Prescribed by and use monitored by consultant rheumatologist
-given with methotrexate, if methotrexate contra-indicated, not tolerated-adalimumab and etanercept may be given as monotherapy.
*severe side effects develop
*no response after 6 months
Discuss the use of Rituximab (MabThera) in the treatment of RA?
-Monoclonal Antibody that depletes the B-cell population
-Given by iv infusion
*two 1000mg i/v infusions given 2 weeks apart
*recommended with methotrexate as possible treatment for adults with severe active RA IF; other drugs havent worked or improves persons condition and doesnt need to be given more often than every 6 months.
Discuss the use of Abatacept (Orencia) in the treatment of RA?
-prevents full activation of T-lymphocytes
-Given by IV infusion;
0,2,4 weeks and every 4 weeks thereafter
-NICE guidance: can be used in combination with methotrexate for: severe active RA or Insufficient response to at least 2 conventional DMARDs
What are the counselling points for methotrexate?
1)with or after food
2)Max 2 units of alcohol per week
3)Once weekly dose
4)Folic acid use
What are the counselling points for ciclosporin?
Avoid grapefruit juice one hour before and after taking
What are the counselling points for Penicillamine?
-Antacids,iron and zinc supplements affect absorption
-before food if possible
What are the counselling points for oral gold?
With or after food
What are the counselling points for sulfasalazine?