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Flashcards in Rheumatoid Arthritis Deck (47):
1

what percentage of people suffer from rheumatoid arthritis?

1 to 3%

2

is rheumatoid arthritis more common in men or women?

three times more common in women

3

when does rheumatoid arthritis exhibit peak onset?

35-55 years

4

what percent of patients are clinically disabled due to aggressive RA and how long does it take for this to occur?

90%
20 years

5

what are the proposed causes of RA

-genetic: HLA-DR4
-Infective
-Immunological
-Hormonal
-Environmental

6

what is the pathophysiology of RA?

Disease of the synovium characterised by:
-infiltration of the synovium by lymphoid cells
-formation of new blood vessels
-Synovial proliferation
-joint destruction

7

What are the earliest signs of RA?

Swelling of the synovial membrane and connective tissue.
Effusion of watery synovial fluid into joint space.

8

what are the late signs of RA?

Joint laxity
severe erosion
deformity due to dislocation

9

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
-non-articular manifestations

10

List the non-articular manifestations of RA?

-Vasculitis
-Anaemia: chronic disease, iron deficiency, vitamin B12/folic acid deficiency
-Rheumatoid nodules
-Dry, gritty eyes (sjogren's syndrome)

11

what are the methods of RA dianosis?

-clinical: ACR/EULAR guidelines
-radiological (x-ray) change
-Laboratory:
haemotology
*ESR; normal 2-5mm/hr, RA >50mm/hr
*CRP; normal 0-6mg/L, RA 10mg/L
serology: RF

12

starting from the bottom list the treatment pyramid for RA

Corticosteroids
^
Cytotoxic drugs
^
DMARD
^
NSAIDS + simple analgesics

13

When does most damage occur in RA?

First 5 years

14

When does max disease activity of RA occur?

first 2 years

15

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.

16

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

17

Discuss the use of NSAIDs for RA treatment?

90% of RA patients receive NSAIDs at some stage
-analgesic effect
-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

18

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

19

Discuss the use of Oral prednisilone for RA treatment?

particularly useful:
-myopathy
-Elderly patients
-DMARDs failed
-dose: 5 - 7.5mg daily or 15mg daily if used intermittently

20

Discuss the use of IV pulse therapy for RA treatment?

-severe refractory disease
-rheumatoid vasculitis
-methylprednisolone 1G over 30-45 minutes as a single dose for 3 days
-best use: adjunct to other drugs!

21

Discuss the use of Intra-articular steroids for RA treatment?

-Joint aspirated and steroid injected aseptically
-large joints: triamcinolone, methylprednisolone
-smaller joints: hydrocortisone

22

What do DMARDs do in terms of RA treatment?

-Not analgesic agents
-Not DIRECTLY anti-inflammatory
-effective in only RA
-Slow acting
-Have joint and non-articular effects
-they lower the ESR + rheumatoid factor titres
-Slows disease progression

23

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.

24

List the order of most frequently used DMARDs

Sulfasalazine, methotrexate, gold, penicillamine

25

Why is methotrexate so widely used?

1)early onset of action
2)good efficacy
3)easily administered
4)High patient tolerability
5)Used in patients with severe inactivated disease

26

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)

27

What are methotrexates Side effects, contraindications and interactions?

side effects:
-not uncommon
-generally mild: 20-30% patients stop treatment
contra-indications:
-pre-existing hepatic disease
-Heavy alcohol use or alcoholism
-impaired renal function
-pregnancy
interactions:
-NSAIDs, oral hypoglycaemics, phenytoin

28

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
-side effects:
*nausea- most common, enteric coated tablets and gradually increase dose.
*haematological rashes
-Contraindications: previous hepatic disease, pregnancy

29

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

30

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

31

Discuss the use of penicillamine and ciclosporin for treatment of RA?

Penicillamine:
-absorption decreased by 50% in presence of food, antacid and iron supplements
ciclosporin:
-previously used in patients for whom other treatment had failed
-now used early in disease, particularly in combination with methotrexate.

32

Discuss the use of Leflunomide for RA treament including side effects, dosing and contra-indications?

Efficacy similar to methotrexate and sulfasalazine
DOSE:
-long t1/2 (15-18 days)
-loading dose 100mg daily for 3 days, then 10-20mg daily
-rapid onset of action- 4 weeks
Side effects:
-skin disorders, diarrhoea, abdominal pain, potential added toxicity when used in combination with other DMARDs.
Contra-indications:
-Pregnancy

33

List the biological therapies used to treat RA

1)TNF alpha inhibitors: infliximab, etanercept, Adalimumab
2)Rituximab
3)Abatacept

34

What do TNF alpha inhibitors do?

Inhibit tumour necrosis factor alpha, a pro inflammatory cytokine.

35

Discuss the use of Infliximab for treatment of RA?

Profound TNF depletion maintained for weeks!
-licensed for RA and crohns disease
-IV dosing:
*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)

36

what are the problems of Infliximab treatment?

-HACA response
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

37

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

38

Discuss the use of treatment of Adalimumab (humira) in treatment of RA

-genetically engineered fusion protein (TNF receptor)
-given subcutaneously:
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

39

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.
-withdrawn if;
*severe side effects develop
*no response after 6 months

40

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
-NICE guidance
*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.

41

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
Cost £10600
-NICE guidance: can be used in combination with methotrexate for: severe active RA or Insufficient response to at least 2 conventional DMARDs

42

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

43

What are the counselling points for ciclosporin?

Avoid grapefruit juice one hour before and after taking

44

What are the counselling points for Penicillamine?

-Antacids,iron and zinc supplements affect absorption
-before food if possible

45

What are the counselling points for oral gold?

With or after food

46

What are the counselling points for sulfasalazine?

After food

47

What are the counselling points for GOLD, penicillamine, sulfasalazine, methotrexate and azathioprine?

report any unexpected bleeding, bruising, sore throat, fever or malaise occuring during treatment