Rheumatoid Arthritis Flashcards

1
Q

What are the risk factors for rheumatoid arthritis?

A
  • Family history
    → 3 times higher if positive Hx in first-degree relative
    → 2 times higher if positive Hx in second-degree relative
  • Genetic predisposition
    → HLA-DRB1 in MHC region is major genetic susceptibility locus for RA
  • Smoking
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2
Q

What is the pathophysiology behind rheumatoid arthritis?

A

Genetic predisposition + immunologic trigger results in T-cell immune response being triggered
→ Inflammatory cytokines (IL-17, TNF, IL-1, IL-6 etc) released by T cells, B cells, macrophages
→ Angiogenesis in synovium leading to synovial cell proliferation and activation
→ Recruitment of inflammatory cells, release of proteases & prostaglandins
→ Ultimately leads to destruction of articular cartilage and underlying bone

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3
Q

What are the specific symptoms observed in rheumatoid arthritis?

A

→ Pain
→ Swelling
→ Erythema and warmth
→ Early morning stiffness > 30min – duration correlated with disease activity
→ Symmetrical polyarthritis (may start unilateral at first)

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4
Q

What are the systemic symptoms commonly seen with rheumatoid arthritis?

A

→ Generalised aching/stiffness
→ Fatigue
→ Fever
→ Weight loss
→ Depression

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5
Q

What are some extra-articular complications of rheumatoid arthritis?

A

→ Eye: episcleritis, scleritis, Sjogren’s syndrome
→ Heart: pericarditis, myocarditis, coronary heart disease, atrial fibrillation, heart failure, nodules
→ Haematology: anemia, Felty’s syndrome, lymphoproliferative disease
→ Lung: Pleural effusion, interstitial lung disease
→ Renal: glomerulonephritis, amyloidosis
→ Skin: Rheumatoid nodule

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6
Q

What are the possible lab findings of rheumatoid arthritis?

A

Autoantibodies (test both bec not all will have both positive)
→ Rheumatoid factor (RF) – positive
→ Anticitrullinated peptide antibodies (ACPA) using anti-CCP assays – positive

Acute phase response (active disease/inflammation)
→ Erythrocyte sedimentation rate (ESR) ↑
→ C-reactive protein (CRP) ↑

FBC – findings consistent with chronic inflammation
→ Hematocrit ↓
→ Platelets ↑
→ WBC ↑

X-Ray/MRI – usually occur at late stage, take at beginning to have a baseline
→ Narrowing of joint space
→ Erosion (around margin of joint)
→ Hypertrophic synovial tissue

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7
Q

What is the diagnosis criteria for rheumatoid arthritis?

A

At least 4 of the following:
→ Early morning stiffness ≥ 1h x ≥ 6/52
→ Swelling of ≥3 joints x ≥ 6/52
→ Swelling of wrist/MCP/PIP joints x ≥ 6/52
→ Rheumatoid nodules
→ +ve RF and/or anti-CCP tests
→ Radiographic changes

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8
Q

What are the goals of treatment for rheumatoid arthritis?

A

Achieve remission or low disease activity
→ At least 6 months
→ Boolean 2.0 criteria (remission: Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1, CRP ≤ 1 mg/dL, Patient Global Assessment (PGA) using 10cm VAS ≤ 2cm)
→ DAS 28 scoring

Achieve maximal functional improvement

Stop disease progression

Prevent joint damage

Control pain

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9
Q

What are the pharm options to treat rheumatoid arthritis?

A

NSAIDs - adjunct to relief pain and minor inflammation

Glucocorticoids - low-dose bridging for DMARD initiation

csDMARDs - Methotrexate, Sulfasalazine, Leflunomide, Chloroquine, Hydroxychloroquine

tsDMARDs - Tofacitinib

bDMARDs - Etanercept, Infliximab, Adalilumab, Tocilizumab, Anakinra

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10
Q

What is the MOA of methotrexate>

A

Folic acid analogue
MOA: Mainly ↑adenosine due to ATIC inhibition
* Also inhibit dihydrofolate reductase
and thymidylate synthetase
* Inc extracellular adenosine level and activation of adenosine A2a receptor
* Anti-proliferative effects on T cells and inhibition of macrophage functions
* Dec pro-inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis

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11
Q

What are the side effects of methotrexate?

A

N/V, mouth and GI ulcers, hair thinning
Leukopenia, hepatic fibrosis, pneumonitis

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12
Q

How does administering folic acid or folinic acid prevent methotrexate toxicity?

A

Admin folic acid or folinic acid 12-24h after methotrexate to decrease toxicity
* Folate cheaper but need high dose as it does not efficiently rescue toxicity due to depletion of N5,N10-Methylene-FH4 from dihydrofolate reductase inhibition
* Folinic acid bypassed dihydrofolate reductase activity, thus more efficient

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13
Q

What is the MOA of sulfasalazine?

A

Metabolized to sulfapyridine (active) + 5-ASA

Mechanism of action not known but poorly absorbed – may be mediated by effect on gut microflora
* Dec IgA and IgM rheumatoid factors
* Suppression of T and B cells, and macrophages
* Dec in inflammatory cytokines e.g. IL-1β, TNF and IL-6

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14
Q

What are the side effects of sulfasalazine?

A

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

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15
Q

What is the MOA of leflunomide?

A
  • Rapidly converted to active metabolite teriflunomide
  • Inhibits dihydrofolate dehydrogenase
  • Dec pyrimidine synthesis and growth arrest at G1 phase
  • Inhibits T cell proliferation and B cell autoantibody production
  • Inhibits NF-κB activation pro-inflammatory pathway
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16
Q

What are the side effects of leflunomide?

A

D, ↑LFT, alopecia, weight gain, teratogenic

17
Q

What is the MOA of chloroquine/hydroxychloroquine?

A
  • Reduced MHC Class II expression and antigen presentation
  • Reduced TNF and IL-1 and cartilage resorption
  • Antioxidant activity
18
Q

What are the side effects of chloroquine/hydroxychloroquine?

A

N, V, stomach pain, dizziness, hair loss, ocular toxicity

19
Q

Which csDMARDs can be used in pregnancy and breastfeeding?

A

Sulfasalazine: need folate supplementation

Chloroquine/Hydroxychloroquine

20
Q

Which csDMARDs are contraindicated with pregnancy and breastfeeding?

A

Methotrexate, Leflunomide

21
Q

What is the MOA of tofacitinib?

A

JAK pathway inhibitor – blocks cytokine production by blocking JAK/STAT-activation of gene transcription

22
Q

What are the side effects of tofacitinib?

A
  • Cytopenia – neutrophils, lymphocytes, platelets, NK cells
  • Immunosuppression → opportunistic infections
  • Anemia – affects JAK2 activation by erythropoietin
  • Hyperlipidemia – inc total, LDL, HDL and triglycerides
23
Q

What are the prescribing considerations for tofacitinib?

A

Give w MTX for mod-severe RA (monotx if MTX-intolerant), also can use for psoriatic arthritis

DO NOT COMBINE WITH BIOLOGIC DMARDS

24
Q

Which bDMARDs are TNF-α inhibitors?

A

Etanercept, Infliximab, Adalimumab

25
Q

What are the side effects of the TNF-α inhibitors?

A

Resp/skin infection, inc risk of lymphoma, optic neuritis, exacerbation of multiple sclerosis, leukopenia, aplastic anemia

26
Q

What are the contraindications for TNF-α inhibitors?

A

Live vaccines, hepatitis B

27
Q

What are the monitoring parameters of TNF-α inhibitors?

A

Screen for latent or active TB

28
Q

Which bDMARDs are IL-6 receptor antagonists?

A

Tocilizumab

29
Q

What are the side effects of tocilizumab?

A

Infections, skin eruptions, stomatitis, fever, neutropenia, inc ALT/AST, hyperlipidemia

30
Q

What bDMARDs are IL-1 receptor antagonists?

A

Anakinra

31
Q

What are the side effects of anakinra?

A

Infections, injection site reactions

32
Q

What are the treatment principles for rheumatoid arthritis?

A

Treatment decisions based on disease activity, safety, patient factors

DMARDs should be started as soon as diagnosis is made
→ MTX should be part of first Tx strategy
→ Consider sulfasalazine/leflunomide if MTX is contraindicated or not tolerated
→ Short-term glucocorticoids should be considered when initiating/changing DMARDs, but tapered and discontinued as rapidly as possible
→ 2nd line: bDMARD preferred – tofacinitinib has high risk of MACE and malignancy (similar to other JAKi)

Treatment should be aimed at reaching a target of sustained remission or low disease activity

Monitor frequently (Q1-3/12) in active disease
→ Adjust if no improvement by 3/12, or target not reached by 6/12

33
Q

What are the precautions and monitoring to be done for bDMARDs/tsDMARDs

A

Pre-treatment screening
* TB (latent/active) – start bDMARD/tsDMARD after completing TB Tx
* Hep B & C – avoid use if untreated disease detected

Vaccination needed before Tx: Pneumococcal, Influenza, Hep B, Varicella zoster, Herpes zoster

Lab screening/monitoring
* CBC w differential WBC count and platelet count
* LFT – ALT, AST, bilirubin, ALP
* Lipid panel

SCr

34
Q

What are the non-pharm strategies for rheumatoid arthritis?

A

Patient Education
→ Provide evidence-based information about disease & management
→ Manage patient’s expectations of disease & treatment
→ Correct patient’s misconceptions

Psychosocial Interventions – e.g. CBT for enhancing self-efficacy & QoL

Resting the inflamed joint/use of splits to support joints and reduce pain
→ Caution against promoting rest for fatigue symptoms – may lead to sedentary lifestyle

Physical Activity
→ Do exercises to maintain range of motion
→ Do exercises to increase muscle strength – avoid contractures & muscle atrophy – prevent decrease in joint stability and improve function
→ Do aerobic exercises to reduce fatigue & pain, improve sleep
→ Avoid high-intensity weight-bearing exercises/activities especially in those w structural damage of lower extremity joints

PT/OT Referral – supervised tailored exercises to disease activity by trained experts

Nutritional & Dietary Counselling
→ Overcome anorexia & poor dietary intake during active RA
→ Weight management if obese – reduce stress on weight-bearing joints
→ Dietary interventions for reducing inflammation e.g. fish oil
→ Dietary interventions for reducing ASCVD risk