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end of y3 > RA > Flashcards

RA Flashcards

1
Q

risk factors for RA

A

1) increased prevalence up to 70 yo
2) peak incidence 40 - 50 yo
3) women 3x more common
4) human leukocyte antigen: HLA-DRB1
5) family history

  • 3x higher odds if 1st degree
  • 2x higher odds if 2nd degree

6) smoking

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2
Q

pathophysiology of RA

A

1) injury -> activation of macrophage in synovial tissue -> secretion of IL-8 and MCV1 -> recruit monocytes

2) monocytes differentiate into macrophage -> +ve feedback to recruit more monocytes -> stimulate release of TNF -> stimulate macrophages to produce

  • more chemokines and cytokines -> induce synovial fibroblast to secrete cytokines and break down connective basement membrane
  • IL-1 that binds to IL-1 receptor -> stimulate more cytokine secretion -> inflammation

3) neutrophils secrete toxic peroxidases and MPO -> further tissue breakdown
4) IL-6 important for recruitment of other cells and stimulate bone destruction

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3
Q

clinical presentation of RA

A

1) inflammation
2) location: symmetrical polyarthritis

  • bilateral
  • small joints: knuckles, row of bones in front of it, wrist, some parts of toes
  • large joints: elbow, shoulder, hip, knees, ankles

3) morning stiffness > 30 mins
4) systemic symptoms

  • more present if > 60 yo
  • generalised aching/stiffness, fatigue, fever, weight loss, depression

5) extra-articular symptoms

  • eyes: Sjogren’s syndrome
  • heart: CAD
  • haematology: Fetty’s syndrome
  • skin: rheumatoid nodules
  • vascular: Rheumatoid vasculitis

6) deformities

  • swan neck (^ at first joint from fingernail), boutonniere (^ in middle joint)
  • loss of physical function and ability to carry out ADL
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4
Q

lab finding for RA

A

1) autoantibodies

  • rheumatoid factor RF (+ve)
    ** not specific for RA, will show for all autoimmune disease
    ** not all RA pt will have +ve RF in early stage
  • anti-CCRP assays (+ve)

2) acute phase response

  • increase ESR, CRP

3) FBC

  • decreased haematocrit
  • increased platelet and WBC

4) radiologic

  • baseline for treatment efficacy monitoring
  • findings
    ** narrowing of joint space
    ** erosion around margin of joint
    ** hypertrophic synovial tissue
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5
Q

diagnosis of RA

A

at least 4 of

1) early morning stiffness ≥ 1 hr for ≥ 6 wks
2) swelling of ≥ 3 joints for ≥ 6 wks
3) swelling of wrist/MCP/PIP joints for ≥ 6 wks
4) rheumatoid nodules
5) +ve RF +/- anti-CCRP test
6) radiographic change

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6
Q

goals of RA therapy

A

1) remission or low disease activity

  • ≥ 6 months of remission/low disease activity
  • Boolean 2.0 inclusion criteria for remission
    ** tender joint count (TJC) ≤ 1
    ** swollen joint count (SJC) ≤ 1
    ** CRP ≤ 1mg/dL
    ** patient global assessment ≤ 2cm
  • gradually taper dose after 6 months of remission

2) maximal functional improvement
3) Stop disease progression
4) prevent joint damage
5) alleviate pain

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7
Q

nonpharmaco for RA

A

1) patient education
2) psychosocial intervention

  • CBT for enhancing self-efficacy and QoL

3) rest inflamed joint, use splint to support joint and reduce pain

  • caution when promoting rest for fatigue symptoms, ensure no sedentary lifestyle

4) physical activities and exercise

  • range of motion exercises: preserve joint motion
  • increase muscle strength -> avoid contractures and muscle atrophy -> prevent decrease in joint stability and improve function
  • aerobic exercise: reduce fatigue and pain, improve sleep
  • avoid high intensity weight bearing exercises

5) physiotherapy, occupational therapy
6) nutrition and diet

  • overcome anorexia and poor dietary intake during RA
  • weight management if obese to reduce stress on weight-bearing joints
  • dietary intervention for reducing inflammation (fish oil) and ASCVD risk
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8
Q

treatment for acute RA flares

A

1) NSAID

  • short term relief of pain and minor inflammation
  • can take PPi to reduce GI SE

2) glucocorticoid

  • low dose bridging therapy when initiating DMARD before DMARD take effect
    ** tapered and discontinued within 3 months
    ** discontinue if bsMARD/tsDMARD initiated
  • ≤ 7.5mg/day prednisolone up to 3 months
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9
Q

types of csDMARD

A

1) methotrexate
2) hydroxychloroquine
3) sulfasalazine
4) leflunomide

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10
Q

initial treatment algorithm with csDMARD

A

1) moderate to high disease state

  • 1st line methotrexate
  • CI methotrexate: hydroxychloroquine, sulfasalazine, leflunomide

2) low disease state

  • hydroxychloroquine (best tolerated) -> sulfasalazine (less immunosuppressive) -> methotrexate (greater dosing flexibility and lower cost) -> leflunomide
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11
Q

methotrexate dose

A
  • initiation dose 7.5mg once weekly
  • dose increment 2.5 - 5mg every 4-12 wks based on response
  • target dose 15mg/wk within 4-6 wks initiation
  • max dose 25mg/wk
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12
Q

methotrexate MOA

A

1) major action

  • increase adenosine levels by AICAR transformylase and ATIC inhibition -> more adenosine acting on adenosine receptor -> anti-inflammatory effect

2) minor action

  • inhibit dihydrofolate reductase -> decrease pyrimidine synthesis and DNA methylation (cause GI effect and hair loss)
  • inhibit thymidylate synthetase

3) overall effect

  • increase extracellular adenosine level and activation of A2a receptor
  • anti-proliferative effect on T cells and inhibition of macrophage function
  • decrease in pro-inflammatory cytokines, adhesive molecules, chemotaxis, phagocytosis
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13
Q

methotrexate SE

A
  • N/V, mouth & GI ulcer, hair thinning
  • leukopenia, hepatic fibrosis, pneumonitis
  • increase transaminases, myelosuppression, TENS, SJS
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14
Q

how to cope with methotrexate SE?

A

folic acid supplementation 5mg/wk 12 - 24 hr after methotrexate dose

  • SE caused by inhibition of dihydrofolate reductase
  • folic acid downstream of dihydrofolate reductase so bypass effects of dihydrofolate reductase inhibition = rescue methotrexate toxicity
  • can also use high dose of folate (cheaper)
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15
Q

methotrexate CI/caution

A

avoid use if CrCl < 30

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16
Q

special population for methotrexate

A

X pregnant cuz teratogenic

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17
Q

hydroxychloroquine dose

A
  • 200-400mg in 1-2 divided dose
  • max 5mg/kg/day
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18
Q

hydroxychloroquine MOA

A
  • reduce MHC class II expression and antigen presentation
  • reduced TNF-alpha and IL-1 and cartilage resorption
  • antioxidant activity
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19
Q

hydroxychloroquine SE

A

N/V, stomach pain, dizziness, hair loss, ocular toxicity (Retinopathy)

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20
Q

hydroxychloroquine CI

A

pre-existing retinopathy

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21
Q

hydroxychloroquine caution

A

G6PD deficiency

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22
Q

sulfasalazine dose

A
  • initiate 500mg OD/BD
  • increase 500mg/wk until 1mg BD maintenance
  • max 3g/day
23
Q

sulfasalazine MOA

A

unknown, poorly absorbed, mediated by gut flora

24
Q

sulfasalazine SE

A

N/V, headache, rash, haemolytic anemia, neutropenia, reversible infertility in men

25
Q

sulfasalazine CI

A

sulfonamide allergies

26
Q

sulfasalazine caution

A

G6PD deficiency

27
Q

leflunomide dose

A
  • 100mg/day for 3 days then 20mg/day maintenance
28
Q

leflunomide MOA

A

rapidly converted to active metabolite teriflunomide

  • inhibit dihydroorotate dehydrogenase
  • decrease in pyrimidine synthesis and growth arrest at GI phase
  • inhibit T cell proliferation and B cell production
  • inhibit NF-Kb activation pro-inflammatory pathway
29
Q

leflunomide SE

A

D, increased transaminase, alopecia, weight gain, teratogenic, myelosuppression

30
Q

leflunomide DDI

A

cholestyramine, activated charcoal

31
Q

leflunomide caution

A
  • very long t1/2
  • cholestyramine (bile salt binding resin) wash out (e.g. pregnancy)
  • avoid use if ALT > 2x ULN
32
Q

leflunomide special population

A

X pregnancy cuz teratogenic

33
Q

what to do if csDMARD not enough to reach target?

A
  • X rely on intraarticular glucocorticoid for symptomatic relief
  • if on methotrexate and not on target then
    ** add bDMARD/tsDMARD
    ** triple therapy: metho, hydroxy, sulfasala (lesser AE risk and cost)
  • if on bDMARD/tsDMARD and not on target then
    ** switch to another one of different class
34
Q

bDMARD MOA

A

bind to cytokines or their receptors to downregulate/inhibit function -> reduce immune and inflammatory responses

35
Q

tldr types of bDMARD

A

1) anti-TNF mab
2) IL-1R antagonist
3) anti IL-6 receptor mab

36
Q

types of anti-TNF mab

A

infliximab (IV infusion), adalimumab (SC), etanercept (SC)

37
Q

SE of anti-TNF-mab

A

1) respiratory infection, skin infection
2) increased risk of lymphoma
3) optic neuritis
4) exacerbation of multiple sclerosis
5) leukopenia, aplastic anaemia

38
Q

anti-TNF mab CI

A

live vaccination, Hep B, HF patient

39
Q

anti-TNF mab monitoring

A

screening for latent/active Tb

40
Q

IL-1R antagonist types

A

anakinra (SC)

  • less active than anti-TNF
41
Q

IL-1R antagonist MOA

A

bind to IL-1 receptor -> block signalling

42
Q

IL-1R SE

A

infection, injection site reaction

43
Q

anti IL-6 mab types

A

tocilizumab (IV)

44
Q

anti IL-6 mab MOA

A

irreversible antagonist of IL-6 receptor

45
Q

anti IL-6 receptor mab SE

A
  • infections, skin eruptions, stomatitis, fever, neutropenia, increase ALT/AST
  • GI perforations
  • hyperlipidemia, interact w CYP (450, 3A4, 1A2, 2C9) substrates
46
Q

types of tsDMARD

A

tofacitinib (PO)

47
Q

what is tofacitinib

A

non-selective JAK inhibitor

48
Q

MOA of tofacitinib

A

bind to JAK protein in cell -> prevent JAK from transphosphorylating associated cytokines and growth factors required -> block activation of JAK/STAT pathway -> inhibit gene transcription responsible for cytokines production

49
Q

AE/precaution of tofacitinib

A

1) cytopenia
2) immunosuppression -> opportunistic infection

  • higher risk of herpes zoster esp in Asians

3) anaemia

  • affect JAK2 activation of erythropoietin

4) hyperlipidemia

  • increase everything cuz involved in metabolism

5) GI perforation

50
Q

tofacitinib MACE and malignancy

A

1) CVS risk factors

  • > 65 yo
  • current/ex smoker
  • obesity
  • PMH of DM, HTN

2) risk factors for malignancy: history/current malignancy
3) risk factors for thromboembolic events

  • PMH of MI, HF, inherited blood clotting disorders, blood clot
  • use of combined hormonal contraceptives or hormone replacement therapy
  • undergoing major surgery, immobility
51
Q

safety concerns for both bDMARD and tsDMARD

A

1) infection/injection site reaction
2) myelosuppression

  • monitor CBC & WBC differential and platelet count

3) infection
4) malignancy risk
5) autoimmune disease
6) cardiovascular disease (HF for TNF-alpha, HTN)
7) hepatic effect (monitor LFT)
8) metabolic effect (monitor lipid panel)
9) pulmonary disease
10) GI perforation (esp IL-6 inhibitor and JAK inhibitor, evaluate abdominal pain/repeated vomiting)
11) thrombosis (Avoid in pt w history of thrombotic events)

52
Q

selection of bDMARD/tsDMARD

A
  • X use more than 1 at the same time
  • CI
    ** hypersensitivity, severe infection, HF (TNF-alpha inhibitors)
53
Q

what to do before initiating bDMARD/tsDMARD

A

1) prevent opportunistic infections

  • pre-treatment screening
    ** latent/active tb: start after completing anti-tb treatment
    ** Hep B, C: avoid if untreated disease detected
  • vaccination required before initiation
    ** pneumococcal, influenza, Hep B, varicella zoster/herpes zoster

2) lab screening/monitoring

  • CBC w differential WBC and platelet count
  • LFT: ALT, AST, bilirubin, ALP
  • lipid panel
  • SCr
54
Q

monitoring for RA treatment

A

1) After initiating csDMARD

  • every 1 - 3 months
  • adjust treatment if no improvement by 3 months or target not reached by 6 month

2) if at target for ≥ 6 months (low disease activity/remission)

  • gradual discontinuation of DMARD
    ** no abrupt discontinuation to prevent flare
    ** if on triple therapy then gradual discontinuation of sulfasalazine over hydroxychloroquine
    ** if on methotrexate + bDMARD/tsDMARD then gradual discontinuation of methotrexate for better disease control

end of y3 (8 decks)

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