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PR3154 FINALS > Osteoarthritis and Rheumatoid Arthritis > Flashcards

Osteoarthritis and Rheumatoid Arthritis Flashcards

1
Q

Name the csDMARDs

A

MTX, sulfasalazine, leflunomide, hydroxychloroquine, ciclosporine

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2
Q

Name the tsDMARD

A

Tofacitinib

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3
Q

Name the 5 classes of bDMARDs and their drugs

A

anti-TNF: infliximab, adalimumab, golimumab, etanecept
IL-1R antag: anakinra
Anti-IL-6:L tocilizumab
Anti-CTLA4: abatacept
Anti CD20: rituximab

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4
Q

What type of drug is MTX (csDMARD) and how can it be administered?

A

Folic acid analogue
PO (variable absorption), SQ or IM

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5
Q

Describe MTX’s MOA

A
  • inhibits ATIC and AICAR = increasing adenosine levels,
  • inhibits dDHFR = decreasing purine synthesis
  • results in anti-proliferative effects on T cells + inhibition of macrophage functions + decrease in in pro-inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis
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6
Q

What are SE (and rare and serious ones) of MTX? (4+3)

A

SE: n&v, mouth and GI ulcers, hair thinning
Rare and serious: leukopenia, hepatic fibrosis and pneumonitis

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7
Q

How can MTX side effects be kept to a minimum

A

administration of concomitant folic acid or folinic acid given 12-24h after MTX to decrease its toxicity levels

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8
Q

Why is folinic acid more effective than folic acid

A

It is rapidly converted to N5 and N10-methylene-FH4, bypassing DHFR activity, making it more efficient at rescuing methotrexate toxicity

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9
Q

What are 3 positive effects of sulfasalazine (csDMARD)

A
  1. decreased IgA and IgM rheumatoid factors
  2. suppression of macrophages, T and B cells
  3. decrease in inflammatory cytokines (eg. IL-1β, TNF, IL-6)
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10
Q

What are SE of sulfasalazine (csDMARD)

A

n&v, HA, rash, hemolytic anemia, neutropenia, reversible infertility in men

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11
Q

What are 4 positive effects of leflunomide (csDMARD)

A
  1. inhibits dihydroorotate dehydrogenase
  2. decreases pyrimidine synthesis and growth arrest at G1 phase
  3. inhibits T cell proliferation and B cell autoantibody production
  4. inhibits NF-κB activation pro-inflammation pathway
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12
Q

What is the consideration for past leflunomide use in pregnant patients?

A

Very long half life (years after dosing) so cholestyramine wash-out may be administered for example before pregnancy

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13
Q

What are SE of leflunomide?

A

diarrhea, liver enzyme elevation, alopecia, weight gain, teratogenic

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14
Q

What are 3 positive effects of hydroxychloroquine (csDMARD)?

A
  1. reduces MHC class II expression and antigen-presentation
  2. reduces TNF-α and IL-1 and cartilage resorption
  3. antioxidant activity
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15
Q

What are SE of hydroxychloroquine?

A

n&v, stomach pain, dizziness, hair loss, ocular toxicity

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16
Q

How should JAK inhibitors like tofacitinib be used?

A

may not be the most useful alone, but have shown great efficacy when used in combination eg. combining tofacitinib with MTX or another csDMARD

monotherapy in patients with intolerance to MTX and is effective in MTX- or multiple bDMARD-refractory RA

tsDMARDs should NOT be combined with bDMARDs

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17
Q

What is the MOA for tofacitinib (tsDMARD)?

A

Janus kinase (JAK) pathway inhibitor, therefore blocking cytokine production

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18
Q

What are SE of tofacinib

A

cytopenia, immunosuppression (resulting in opportunistic infections), anemia, hyperlipidemia

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19
Q

Arrange anti-TNF bDMARDs according to immunogenecity

A

The more humanised the biologic, the less immunogenic it is (infliximab > adalimumab > golimumab > etanercept)

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20
Q

What are anti-TNF bDMARD half lives like?

A

Monoclonal antibodies have half-lives of 1-2 weeks while etanercept has a half-life of about 70 hours

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21
Q

How does anakinra (IL-1R antag) compare to anti-TNF bDMARDs?

A

less effective than anti-TNF bDMARDs

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22
Q

What are SE of anakinra (IL-1R antagnoist)

A

infections, injection site reactions

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23
Q

What are SE of tocilizumab (IL-6R antagonist)

A

Infections, skin eruptions, stomatitis, fever, neutropenia, increase in ALT/AST, hyperlipidemia, interacts with CYP450 3A4, 1A2 or 2C9 substrates

24
Q

What are SE of abatacept (anti-CTLA4Ig)

A

respiratory infection in COPD, increased incidence of lymphoma

25
Q

What are SE of rituximab (anti-CD20)

A

rash in first dose, respiratory infection in COPD

26
Q

What are contraindications to bDMARD therapy

A

Live vaccination
Hepatitis B and C

27
Q

What are the risk factors for OA?

A

Genetic predisposition
Anatomic factors (bow-legged, or knocked-knee)
Joint injury (from sports or surgery)
Obesity (greater weight on load-bearing joints, metabolic OA)
Aging (changes in ECM)
Gender
Occupation

28
Q

Explain the pathophysiology of OA

A

articular cartilage damage → chondrocyte activity increases

Abberant chondrocytes → more breakdown

subchondral bone releases vasoactive peptides and MMP → increases collagen breakdown

Both of these factors lead to cartilage loss and chondrocyte apoptosis → forms fibrillations in cartilage and cartillage “shards”

Cartillage shards cause inflammatory and pathologic changes in joint capsule and the synovium, mediated by TNF-α, IL-1, PGE2 and NO → effusion and synovial thickening

Subchondral bones rub against each other → more brittle and decreased weight bearing ability → development of sclerosis, microfractures and osteophytes

29
Q

What are osteophytes

A

sideway extention from bones as the joint is not there for protection

compensatory structures to stabilise osteoarthritic joints

30
Q

What are the 3 main occurrences in OA pathophysiology

A
  1. Cartilage degradation
  2. Bone remodelling and osteophyte formation
  3. Synovial inflammation
31
Q

Describe the clinical presentation of OA

A

pain, swelling, erythema and warmth (from inflammation),

morning stiffness < 30 mins
limited joint movement (loss or RoM)
functional limitation
instability
asymmetrical polyarthritis (typically on weight bearing joints)

32
Q

Describe pain onset and when the pain worsens in OA

A

onset is insidious (slow progression over the years) and is worse with joint use and relieved by rest

33
Q

How is OA diagnosed?

A
  • Clinical diagnosis can be made without imaging in:
    • ≥ 45 years old, activity-related joint pain (in one or a few joints), morning stiffness ≤ 30 mins
34
Q

When should additional testing be done for OA?

A

younger patients
presence of atypical signs and symptoms that suggest other diagnoses: hx of recent trauma, rapidly worsening sx or deformity or concerns for infection or malignancy

35
Q

What are goals of treatment in OA

A

pain relief (and of inflammation if any)
improving or preserving RoM ,joint fx and QoL

36
Q

What are NPM for OA? (3)

A
  1. Exercise (mainstay)
  2. Weight management
  3. Information and support (empower)
37
Q

What are pharmacological treatments for OA?

A
  1. TOP NSAIDs
  2. PO NSAIDs or coxibs
  3. PO paracetamol/tramadol
  4. IA glucocorticoid
38
Q

What are risk factors for GI bleeds or ulcers? (4)
HANG
(if 3 or 4 RFs present, use coxib instead)

A
  1. history of ulcers
  2. > 65 yo
  3. NSAIDs (high dose or chronic)
  4. glucocorticoids, antiplatelet or anticoagulant use
39
Q

What are risk factors for NSAID-induced AKI

A

CKD, volume depletion (due to HF, nephrotic syndrome, cirrhosis), severe hypercalcemia, drugs like aminoglycosides, amphotericin B, radiocontrast material, diuretics, ACEi, ARBs, and age > 65 yo

40
Q

What eGFR value should NSAIDs be avoided in

A

eGFR < 15

41
Q

Describe the pathophysiology of RA

A

Genetic predisposition and immunologic triggers cause citrullinated antigens to be picked up by APCs → trigger T-cell mediated immune response (inflammatory response)

Inflammation → angiogenesis in the synovium and synovial cell proliferation → recruit inflammatory cells → production of inflammatory cytokines (IL-17, TNF, IL-1 and IL-6) → signal via JAK pathway → destruction of articular cartilage and underlying bone

Synovial cell proliferation → pannus invasion → destruction of articular cartilage and underlying bone

42
Q

Describe the clinical presentation of RA

A

pain, swelling, erythema and warmth (inflammation MUCH worse than OA)

morning stiffness > 30 mins (pts usually take a long time to get out of bed)
symmetrical polyarthritis (usually starts w small joints of hands and legs)

43
Q

How should an RA diagnosis be made (based on sx) (4/6)

A
  • Diagnosis should come with 4 of the following 6:
    • Early morning stiffness ≥ 1h x ≥ 6 weeks
    • Swelling of ≥ 3 joints x ≥ 6 weeks
    • Swelling of wrist/MCP/PIP joints x ≥ 6 weeks
    • Rheumatoid nodules
    • RF +ve and/or anti-CCP tests
    • Radiographic changes
44
Q

What are relevant lab findings for RA diagnosis?

A
  • Autoantibodies → RF +ve, anti-CCP assays +ve (both of these tests being negative does NOT exclude an RA diagnosis as they may show up as negative in early disease stages)
  • Acute phase response → ESR increase, CRP increase
  • FBC → decreased hematocrit, increased platelets, increased WBC
  • Radiologic X-ray or MRI → narrowing of joint space, erosion (around joint margin), hypertrophic synovial tissue
45
Q

What are goals of treatment for RA?

A

remission or low disease activity for at least 6 months (achieve maximal function improvement, stop disease progression, prevent joint damage, control pain)

46
Q

What is considered remission according to the Boolean 2.0 criteria? (4)

A
  • Tender joint count (TJC) ≤ 1
  • Swollen joint count (SJC) ≤ 1
  • CRP ≤ 1mg/dL
  • Patient global assessment (PGA) using 10ccm VAS ≤ 2cm
47
Q

DMARDs are first line therapy for RA, explain how they help with the disease.

A

DMARDs alter disease progression and help to slow/prevent radiographic joint damage, improve physical function and lower ESR/CRP

48
Q

How and when should first line treatment for RA (csDMARDs) be started?

A
  • DMARDs should be started as soon as the diagnosis is made (MTX should be part of first treatment strategy) (slow onset of action between weeks and months)
  • Sulfasalazine, leflunomide or hydroxychloroquine should be considered if MTX is contraindicated or not tolerated
49
Q

Which drugs are preferred for low and mod-high disease activity in RA patients

A

low: hydroxychloroquine (better tolerated)
mod-high: MTX

50
Q

How should MTX be dosed?

A

MTX should be started 7.5mg OW
increased by 2.5 to 5mg per week,
up to a target dose of 15mg a week within 4-6 weeks of initiation (fast to control disease as soon as possible)

51
Q

What dose of folic acid should MTX be given with?

A

5mg OW

52
Q

How should other csDMARDs be initiated?

A
  • Sulfasalazine: initiate w 500 mg OD or BD, increase by 500 mg/week to 1g BD (maintenance), max 3000 mg/day
  • Hydroxychloroquine: 200 – 400 mg in one or two divided doses (max 5 mg/kg/day)
  • Leflunomide: 100 mg/day x 3 days (optional loading dose), 20 mg/day (maintenance dose)
52
Q

How should glucocorticoids be used in RA?

A

Short-term low-dose glucocorticoids can be dded when starting or changing DMARDs for moderate to high RA disease activity
(≤ 7.5mg/day prednisolone up to 3 months)

Discontinue if bDMARDs or tsDMARDs are started

53
Q

What is triple therapy in csDMARDs?

A

MTX
hydroxychloroquine
sulfasalazine

54
Q

If csDMARDs do not work, which of the other DMARDs are preferred?

A

bDMARDs are preferred (tsDMARD carries a higher risk for major adverse cardiovascular events (MACEs) and malignancy, compared to TNFα inhibitors for patients with risk factors)

55
Q

What 3 things should be screened for and checked before initiating bDMARDs or tsDMARDs

A
  1. Pre-treatment screening → for TB (start after completing anti-TB treatment), and for hepatitis B and C (avoid if untreated disease is detected)
  2. Vaccination required before initiation → pneumococcal, influenza, hepatitis B, varicella zoster
  3. Laboratory screening and monitoring → CBC with differential white count and platelet count, LFT (ALT, AST, bilirubin, ALP), lipid panel and SCr

PR3154 FINALS (6 decks)

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