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3154 MSK > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

What is RA?

A

RA is a chronic autoimmune inflammatory systemic disease

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2
Q

Prevalence and incidence of RA

A
  • Affects 1% of the popln
  • Can occur at any age but has incr prevalence up to the 7th decade of life
  • Peak incidence: 40-50y
  • 3x more common in women than men
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3
Q

Genetic predisposition for RA

A
  • HLA-DR4 and HLA-DR1 in MHC region
  • More likely if parents are RF +ve
  • Twin
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4
Q

Contribution of environmental factors to RA

A
  • Cigarette smoke
  • Pathogen (e.g., gut bacteria)

=> cause modification of own antigens (IgG antibodies, type II collagen, vimentin)

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5
Q

[Pathogenesis of RA]

A
  1. Genetic predisposition + immunologic trigger
  • Citrullination process: citrullinated antigens are picked up by antigen-presenting cells (e.g., type II collagen and vimentin can get modified through citrullination process - amino acid arginine converted to cirtulline)
  1. T-cell mediated immune response
  • Produced by T cells, B cells, macrophages, fibroblast-like synoviocytes
  • Recruitment of inflammatory cytokines that signal via the Janus Kinases (JAKs)
  1. Inflammatory response, Angiogenesis in synovium, Synovial cell proliferation, Pannus invasion
  2. Release of proteases (breakdown cartilage) and prostaglandins

=> LEAD TO: destruction of articular cartilage and underlying bone

  • Incr RANKL on T cell, bind to RANK on osteoclast; stimulates osteoclasts to break down bone
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6
Q

[Pathogenesis of RA]

How are immune cells involved?

  • Proliferation
  • Cytokine production
  • Adhesion and trafficking
A

All are involved:

  • Proliferation
  • Cytokine production
  • Adhesion and trafficking
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7
Q

Clinical Presentation of RA

(6 in total)

A

1. Inflammation

  • Pain, Swelling, Erythema, Warmth

2. Early morning stiffness >30min

  • duration correlate with disease activity

3. Symmetrical polyarthritis (may start unilateral first)

  • Small joints (typically start with MCP and PIP of hand, IP of thumb, wrist, MTP of toes)
  • Large joints (elbows, shoulders, hips, knees, ankles)

4. Systemic symptoms (due to cytokines in the blood)

  • Generalized aching/stiffness
  • Fatigue, malaise, weakness (could be due to Hb drop)
  • Fever
  • Weight loss
  • Low appetite
  • Depression

Particularly present in those with disease onset >60y, and up to one-third of those with acute onset polyarthritis

5. Extra-articular complications (due to cytokines in the blood)

  • Eye: scleritis
  • Heart: myocarditis, CAD, AF, HF, nodules, atherosclerosis
  • Hematology: anemia
  • Lung: chronic cough, SOB, pleural effusion, interstitial lung fibrosis
  • Renal: glomerulonephritis
  • Skin: rheumatoid nodules
  • Vascular: PVD, rheumatoid vasculitis
  • Musculoskeletal: osteoporosis

6. Deformities (chronic)

  • Swan neck (fingers)
  • Boutonniere deformity (fingers)
  • MCP Subluxation (fingers) / MTP subluxation (toes)
  • Ulnar deviation (wrist/fingers)
  • Rheumatoid nodules (elbow)
  • Popliteal cyst (back of knee)
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8
Q

Describe the pain in RA (wrt to time of the day, activity etc.)

A
  • Usually insidious onset
  • Worse in the morning or after inactivity
  • Worse after rest
  • Relieved with exercise (gets better across the day with movement)
  • Nocturnal pain
  • Chronic with acute/subacute flares/symptoms

VS OA which is pain on movement, and worse at the end of the day, relieved with rest and no nocturnal pain

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9
Q

Laboratory findings in RA:

A

1. Autoantibodies

  • Rheumatoid factor (RF) - positive
  • Anti-citrullinated peptide antibodies, using anti-CCP assays - positive (more specific than RF)

However, negative does not mean not RA, 30% may not have positive autoantibodies at early stage

2. Acute phase response

  • Incr ESR
  • Incr CRP

3. FBC

  • Hematocrit/Hb dcr (anemia of chronic diseases)
  • Incr platelets
  • Incr WBC

Radiologic (X-ray/MRI)

  • Narrowing of joint space
  • Erosion
  • Hypertrophic synovial tissue
  • Decrease bone density

Usually only can see in later stages

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10
Q

Diagnosis of RA:

A

At least 4 out of 6 of the following:

  • Early morning stiffness >=1h for >=6w
  • Swelling of >=3 joints for >=6w
  • Swelling of wrist/MCP/PIP joints on hands for >=6w

DIP - distal, CMC - 1st carpometacarpal joints are EXCLUDED, these are affected in OA instead

  • Rheumatoid nodules
  • Positive RF and/or anti-CCP tests
  • Radiographic changes
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11
Q

Diagnosis of RA (based on 2010 American College of Rheumatology):

A

Score of >=6 out of 10: RA

Criteria:

  • Joint involvement
  • Serology (RF and ACPA)
  • Acute phase reactants
  • Duration of symptoms >= 6 weeks
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12
Q

Goals of Treatment in RA:

A

Achieve remission or low disease activity

  • At least 6 months
  • Boolean 2.0 criteria for remission (Tender joint count =<1; Swollen joint count =<1; CRP =<1mg/dL; Patient Global Assessment (PGA) using 10cm VAS =<2cm)
  • Index-based definition for disease activity index/score (SDAI/CDAI/DAS 28)

Achieve maximal functional improvement
Stop disease progression
Prevent joint damage
Control pain

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13
Q

RA - NSAIDs use

A

NSAIDs are used as adjuncts to DMARDs, to relief pain and minor inflammation (effect in 1-2 weeks)

They do not alter the course of the disease

Comparable efficacy between NSAIDs and COX-2 inhibitors

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14
Q

RA - Glucocorticoid use

*Use with DMARDs
*Example of doses as well

A
  1. Used as low-dose bridging therapy when initiating DMARDs
  • E.g., PO Prednisolone <7.5mg /day
  • Short-term glucocorticoids should be considered when initiating/changing csDMARDs for mod/high RA activity, but tapered and discontinued within 3 months (as rapidly as feasible); discontinued if starting bDMARD or tsDMARD

NOT recommended to use as continuous low-dose therapy due to SE and availability of many DMARD choices (might consider only in difficult-to-control patients)

  1. May be used to control flares
  • E.g., intraarticular injections, may be repeated q3monthly; but not more than 2-3x per year per joint (risk of tendon atrophy and accelerated joint destruction)
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15
Q

RA - DMARDs use, onset

A

Alters disease progression

  • Slow/prevent radiographic joint damage
  • Improve physical joint function
  • Lower ESR/CRP

Onset is SLOW, weeks to months

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16
Q

When should DMARDs be started?

A

Start soon as diagnosis is made because:

  • Maximal joint damage occurs within first 2 years
  • 30% have radiographic erosions at diagnosis, 60% will have by 2 years
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17
Q

Treatment principles for RA

A
  • DMARDs should be started as soon as diagnosis is made
  • Treatment should be aimed at reaching a target of sustained remission or low disease activity
  • Monitor frequency in active disease (q1-3months); tx should be adjusted if no improvements by 3 months or target not reached by 6 months

=> Continue if improved by 3 months AND target achieved at 6 months

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18
Q

Choice of 1st line DMARDs

A

csDMARDs tried first:

  • Methotrexate is 1st line (long-term efficacy, acceptable toxicity, low cost)
  • Consider Sulfasalazine / Leflunomide if MTX is contraindicated or not tolerated

Short-term GC:

  • Short-term glucocorticoids should be considered when initiating/changing csDMARDs, but tapered and discontinued within/not more than 3 months (as rapidly as feasible)
19
Q

[Management of RA - DMARD naive patient]

Patient with moderate-high disease activity

A
  • Methotrexate monotherapy preferred (Sulfasalazine or Leflunomide if contraindicated/intolerance to MTX)
  • Add low-dose glucocorticoid when initiating DMARD to alleviate symptoms prior to DMARD onset (if necessary)
20
Q

[Management of RA - DMARD naive patient]

Why is hydroxychloroquine not considered for pt with mod-high disease activity?

A

EULAR:

  • Hydroxychloroquine is a weak DMARD, may be used in pt with early, low disease activity without poor prognostic factors; in whom the other 3 csDMARDs are contraindicated/not tolerated

Note that hydroxychloroquine widely used in other disease states such as malaria, SLE; not so much used in RA except in triple therapy

(Least potent, but best tolerability)

21
Q

[Management of RA - DMARD naive patient]

Patient with low disease activity

A

Most to least preferred:

  • Hydroxychloroquine (better tolerated)
  • Sulfasalazine (less immunosuppressive than MTX, avoid MTX SEs)
  • Methotrexate (greater dosing flexibility, lower cost than Leflunomide)
  • Leflunomide

However, note that this is conditional, and MTX may still be preferred if pt is at the higher end of the low disease activity range, and if pt has poor prognostic factors

22
Q

[Management of RA - DMARD naive patient]

MTX monotherapy dose:

  • Initiation
  • Dose increment
  • Target dose
  • Max dose
  • Rescue therapy dose
A

Each tablet is 2.5mg

Initiation dose: 7.5mg weekly (3 tablets)

Dose increment: 2.5-5mg per week; every 4-12 weeks based on response

Target dose: 15mg/week within 4-6 weeks of initiation

Max dose: 25mg/week (10 tablets)

Rescue therapy: folic acid 5mg/week - to be given 12-24h after MTX to minimize MTX toxicity

23
Q

[Management of RA - DMARD naive patient]

Pt started on csDMARD, improved at 3 months and achieved target at 6 months:

A

Continue treatment, and consider dose reduction in sustained remission

24
Q

[Management of RA - DMARD naive patient]

Pt started on csDMARD, no improvement at 3 months or target not achieved by 6 months:

A

Move on to management of RA (NOT at target on csDMARD)

DMARD should be adjusted to reduce disease activity

DO NOT rely on intraarticular glucocorticoid for symptom relief

25
Q

[Management of RA - NOT at target on DMARD]

What are poor prognostic factors?

A

Poor prognostic factors: higher risk of disease damaging the joints

  • High acute phase reactant levels
  • High swollen joint counts
  • High levels of RF/ACPA
  • Presence of early joint damage/erosion
  • Persistently mod-high disease activity (after csDMARD therapy)
  • Failure of >=2 csDMARDs
26
Q

[Management of RA - NOT at target on DMARD]

Patients with MTX but not at target:

A
  1. Add bDMARD or tsDMARD (if poor prognostic factors are present)
  • Maximize improvement quickly
  • bDMARD - TNFa inhibitor should be tried first
  • tsDMARD and IL-6 inhibitors may have some advantage over bDMARDs
  • Discontinue glucocorticoids
  1. Add csDMARDs: Hydroxychloroquine and Sulfasalazine to Methotrexate (Triple therapy)

FYI: triple therapy can also be hydroxychloroquine + sulfasalazine + Leflunomide

  • Less adverse events and lower cost
  • Glucocorticoids - 3 months
27
Q

[Management of RA - NOT at target on DMARD]

Patients with bDMARD/tsDMARD but not at target:

A

Switch to bDMARD or tsDMARD of a different class/MOA

  • If first DMARD was TNF-a inhibitor or IL-6 inhibitor, may try a second TNF-a inhibitor or IL-6 inhibitor

Note: pt would still be on MTX as well

28
Q

[Management of RA - NOT at target on DMARD]

Pt has started on triple therapy/bDMARD/tsDMARD and improved at 3 months and achieved target at 6 months:

A

Continue, consider dose reduction in sustained remission

29
Q

[Management of RA - patients at target >=6 months]
i.e. low disease activity or remission for >=6 months

What should be done?

A

Guidelines conditionally recommend:

Continuation > Dose reduction / Increase interval > Gradual discontinuation > Abrupt discontinuation
(of any of the DMARDs)

Note that if pt in remission for <6m, CANNOT reduce dose or withdraw; only may reduce dose/discontinue if pt has been at target for 6 months and more

30
Q

[Management of RA - patients at target >=6 months]

Why must discontinuation of DMARD be done gradually with dose tapering?

A

Abrupt discontinuation can result in flares

31
Q

[Management of RA - patients at target >=6 months]

Patient was on triple therapy:

A

If patient wants to discontinue one csDMARD,

Gradual discontinuation of Sulfasalazine is conditionally recommended over hydroxychloroquine

  • Due to lower adverse events a/w Hydroxychloroquine, has better treatment persistence
32
Q

[Management of RA - patients at target >=6 months]

Patient was on MTX + bDMARD/tsDMARD:

A

If pt wants to discontinue one drug:

Gradual discontinuation of MTX is conditionally recommended over bDMARD/tsDMARD for better disease control

However, note that may choose to discontinue MTX instead as well - considerations: comorbidities, risk of infections, cost concerns etc.

There is no difference in clinical outcome when either bDMARD/tsDMARD or csDMARD is tapered first

33
Q

Safety concerns of bDMARDs and tsDMARDs

A
  • Injection site/infusion reactions for bDMARDs
  • Myelosuppression - monitor CBC with WBC differentials and platelet counts
  • Infections - URTI, TB, hepatitis, opportunistic infections; pre-DMARD vaccination, screening and treatment
  • Malignancy risk - similar risk b/w bDMARD and tsDMARD; nonmelanoma skin cancer most common, counsel to wear sunscreen
  • Autoimmune disease - SLE, demyelinating peripheral neuropathies
  • Cardiovascular disease - HF (AVOID TNF-a inhibitors in NYHA class III and IV), HTN
  • Hepatic effect - incr aminotransferase, monitor LFT (IL-6 inhibitor, MTX, Leflunomide)
  • Metabolic effect - hyperlipidemia, monitor lipid panal (IL-6 inhibitor and tsDMARD)
  • Pulmonary disease - pulmonary toxicity, use with caution in interstitial disease
  • Gastrointestinal perforation - risk factors, IL-6 inhibitor and JAK inhibitor, some reports for anti-CD20 rituximab
  • Thrombosis - avoid in pt with hx of thrombotic events, IL-6 inhibitor and JAK inhibitor
34
Q

[Selection of bDMARD/tsDMARD]

Contraindications:

A
  • Hypersensitivity to components for the formulation
  • Severe infections (e.g., sepsis, TB, opportunistic infections)
  • HF (TNF-a inhibitors)
35
Q

[Selection of bDMARD/tsDMARD]

Can multiple bDMARDs/tsDMARDs be used at the same time?

A

No, cannot use more than 1 bDMARD or tsDMARD at the same time

Additionally, bDMARDs and tsDMARDs cannot be used tgt

=> risk of additive effects, high risk of immunosuppression and opportunistic infections

36
Q

[Selection of bDMARD/tsDMARD]

Which bDMARD may result in loss of efficacy? Why?

A

TNF-a inhibitors may cause the formation of anti-drug antibodies (ADA) which could result in loss of efficacy

37
Q

[Selection of bDMARD/tsDMARD]

Why is bDMARD preferred over tsDMARD?

A

Tofacitinib carries higher risk for major adverse cardiovascular events (MACEs) and malignancy (for individuals with the risk factors)

Risk should be told to pt for SDM

Risk factors:

(CVD)

  • Age >65
  • Hx of current or past smoking
  • Other CVD risk factors: diabetes, obesity, hypertension

(Malignancy)

  • Other risk factors for malignancy: current of hx of malignancy other than successfully treated NMSC

(Thromboembolic events)

  • Risk factors for thromboembolic events (hx of MI, HF, cancer, inherited blood clotting disorders, hx of blood clots)
  • Pts taking combined hormonal contraceptives or HRT
  • Pts undergoing major surgery
  • Pts who are immobile
38
Q

[Initiation of bDMARD/tsDMARD]

What is required prior to initiation of bDMARD/tsDMARD?

A
  1. Pre-treatment screening
  • TB (latent/active) => start after completing anti-TB tx
  • Hep B and C => avoid if untreated disease detected
  1. Vaccination
  • Pneumococcal
  • Influenza
  • Hep B
  • Varicella zoster, shingles
  1. Lab screening/monitoring: baseline + regularly after initiation
  • CBC with differential white count and platelet count (myelosuppression)
  • LFT (incr aminotransferase)
  • Lipid panel (hyperlipidemia)
  • SCr
39
Q

Patient has an infection while on bDMARD/tsDMARD, what should be done?

A

Stop the bDMARD/tsDMARD, continue antibiotic for bacterial infection, and restart DMARD after infection resolves

40
Q

Patient is going for an elective surgery while on bDMARD/tsDMARD, what should be done?

A

Discuss with rheumatologist, e.g., hold medication before surgery 2 weeks in advance

41
Q

[Non-pharmacological interventions in RA]

A
  1. Patient education regarding RA and management
  2. Psychosocial interventions
  • CBT for enhancing self-efficacy/QoL
  1. Rest inflamed joint
  • *Caution against promoting rest as may lead to sedentary lifestyle
  1. Use splint to support joints/reduce pain
  2. Physical activity and exercise
  • Maintain range of joint motion
  • Increase muscle strength => avoid contractures and muscle atrophy, can prevent decrease in joint stability, reduce fatigue and pain
  • Improve sleep
  • AVOID high-intensity weight-bearing exercises/activities (e.g., recommend swimming instead)
  1. Physical therapy, Occupational therapy
  2. Nutritional and dietary counseling
  • Weight management if obese
  • Dietary interventions for reducing inflammation (e.g., fish oil)
  • Dietary interventions for reducing ASCVD risk
42
Q

Other non-pharm (IC10)

A
  • Physical therapy
  • Occupational therapy
  • Transcutaneous electrical nerve stimulation (TENS)
  • Synovectomy (remove synovium that lines the joint, reduce inflammatory synovial mass)
  • Tendon repair
  • Joint fusion
  • Total joint replacement
43
Q

Pharmacist role in RA

A
  • Pt education (disease, pharmacotherapy, non-pharmacological, SE management)
  • Med selection
  • Pre-biologic and immunosuppressant workup
  • Liaison for biologic assistance programs
  • Vaccination updates
  • Therapy monitoring

3154 MSK (12 decks)

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