23 - Rheumatoid Arthritis Flashcards Preview

Year 3 - Clinical (Winter) > 23 - Rheumatoid Arthritis > Flashcards

Flashcards in 23 - Rheumatoid Arthritis Deck (46)
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1
Q

Describe the burden of RA

A
  • Associated w/ reduced QOL, disability, decreased life expectancy, and increased risk of CV disease and mortality
  • Can be associated w/ systemic manifestations (many other organs in the body)
2
Q

Definition of RA

A
  • Chronic, systemic autoimmune inflammatory disease characterized by symmetric and erosive polyarthritis causing pain, stiffness, and fatigue
  • If not treated appropriately, can result in joint destruction and severe disability that can disrupt multiple aspects of a px life
  • Lifelong condition but can be in remission w/ appropriate pharm therapy
3
Q

Pathophysiology of RA

A
  • Most px w/ RA form antibodies called rheumatoid factors and anticitrullinated protein antibody (ACPA)
  • Involves a complex interaction of many extracellular and intracellular molecules (inflammatory factors)
    • Inflammatory mediators including tumour necrosis factor-alpha, IL inhibitors (IL-1, IL-6), T-cell, memory beta cells
4
Q

Risk factors for RA

A
  • Genetic predisposition
  • Exposure to unknown environmental factors
  • Age, gender, obesity, smoking
5
Q

Difference in clinical presentation of OA vs. RA

A
  • Onset -> RA = earlier (25-50 y/o); OA = later (usually > 40 y/o)
  • Development -> RA = more rapidly; OA = slow
  • Symmetrical -> RA = symmetrical; OA = usually non-symmetrical onset
  • Pain -> RA = pain decreases w/ activity and increases w/ inactivity; OA = pain worsened by activity
  • Tenderness -> RA = common; OA = uncommon
6
Q

Difference in joints affected for OA vs. RA

A
  • OA = knees, hip, hands

- RA = classically arthritis of the hand (especially PIP, MCP, and wrist joints)

7
Q

Difference in morning stiffness for OA vs. RA

A
  • OA = generally < 1 h

- RA = > 1 h

8
Q

Difference in presence of systemic sx of OA vs. RA

A
  • OA = none

- RA = common

9
Q

Difference in lab values of OA vs. RA

A
  • OA = normal

- RA = ESR/CRP; RF/ anti-CCP

10
Q

Difference in radiographs of OA vs. RA

A
  • OA = joint space narrowing, osteophytes

- RA = joint space narrowing, erosions

11
Q

Sx of RA

A
  • Joint pain and stiffness > 6 weeks, stiffness lasts > 1 h
  • May experience fatigue, weakness, low-grade fever, loss of appetite
  • Muscle pain and afternoon fatigue may be present
  • Joint deformity is generally seen late in the disease
12
Q

Signs of RA

A
  • Joint involvement is frequently symmetrical
  • Tenderness and warmth and swelling over affected joints (usually hands and feet)
  • Systemic sx may be present
  • Rheumatoid nodules may be present
13
Q

What are the 2 groups of RA px?

A
  1. Early RA (ERA) = px w/ sx of less than 3 months duration

2. Established disease = px have sx due to inflammation and/or joint damage

14
Q

Clinical course and prognosis of RA

A
  • 80% have cyclic-type of progressive disease course
  • Time to diagnosis and initiation of DMARD therapy is crucial
  • Early diagnosis = w/in 6 months of the onset of joint sx
  • Joint damage begins w/in 2 years of sx
15
Q

How is RA diagnosed?

A

ACR/EULAR 2010 criteria requires 6 or more points

16
Q

Role of lab values in the diagnosis of RA

A
  • Labs normal > 30% of the time
  • RF or anti-CCP positive px = worse prognosis
  • RF detectable in 60-70% of px
  • Anti-CCP detectable in 50-85% (can be detected years before diagnosis)
  • Acute phase reactants may also be elevated -> not specific to rheumatic disease (C-reactive protein, erythrocyte sedimentation rate)
17
Q

Other diagnostic tests for RA

A
  • Joint fluid aspiration may show increased WBC counts w/o infection, crystals
  • Joint radiographs may show periarticular osteoporosis, joint space narrowing, or erosions
18
Q

DAS28 assessment tool for RA

A
  • Number of swollen joints at 28 sites
  • Number of tender joints at 28 sites
  • Pt estimate of global status
  • ESR or CRP value
  • Score > 5.1 = high disease activity
  • Score 3.2 – 5.1 = moderate disease activity
  • Score 2.6 to < 3.2 = low disease activity
  • Score < 2.6 = remission
19
Q

Goals of therapy for RA

A
  • Fully control signs and sx of the disease and halt radiographic progression and joint damage
  • Obtain rapid clinical improvement w/ a goal of 50% improvement w/in 3 months and ideally clinical remission
  • Remission can be defined using multiple composite disease activity measures
  • Tx should alleviate pain, stiffness and fatigue; prevent any further joint damage and destruction; maintain physical function and work capacity; and maximize QOL
20
Q

General tx approach for RA

A
  • Both ACR and EULAR guidelines recommend a tx target of low disease activity or remission in px w/ early and established RA
  • Treat-to-target approach; adjust tx every 1-3 months as guided by regular monitoring of disease activity using composite measures of disease activity
  • Several tx options
  • Main pharmacological options include:
    • Disease modification w/ conventional synthetic DMARDs, biologic agents, targeted synthetic DMARDs, and glucocorticoids
    • Sx relief w/ NSAIDs
21
Q

Algorithm for RA tx

A
  • DMARD-naïve w/ low to high disease activity = DMARD (MTX preferred) +/- prednisone
  • Moderate-high disease activity = combination DMARD or TNFi +/- MTX or non-TNF biologic +/- MTX or tofacitinib +/- MTX
  • Moderate-high disease activity w/ single TNFi failure = non-TNF biologic +/- MTX or TNFi +/- MTX
    • 2nd option = non-TNF biologic or tofacitinib +/- MTX
  • Moderate-high disease activity w/ non-TNF biologic failure = another non-TNF biologic +/- MTX
    • 2nd option = TNFi in TNFi tx naïve or tofacitinib +/- MTX
22
Q

Methotrexate for RA (category, appropriateness, efficacy, onset, and safety)

A
  • Category -> synthetic DMARD
  • Appropriateness -> preferred DMARD w/ respect to efficacy and safety; should be the first DMARD used in px w/ RA unless CI
  • Efficacy -> most effective traditional oral synthetic DMARD
  • Onset -> 4-6 weeks in most px; effective for all levels of disease activity
    • SQ MTX weekly is recommended for those who lose benefit over time
  • Dose -> titrated to a usual max dose of 25 mg per week by rapid dose escalation
  • Initial combination therapy w/ traditional DMARD should be considered for certain px
23
Q

Safety of MTX

A
  • Best SE to efficacy ratio of any other synthetic or biological DMARD
  • Common SE = stomatitis, N, diarrhea, and possibly alopecia (can decrease incidence of some SE by giving folic acid tab)
  • Generally, well tolerated in doses for RA
  • Significant alcohol consumption should be strictly avoided
24
Q

MTX lab monitoring

A
  • CBC+, PLT, ALT, alk phos, albumin, sCr
    • Months 1-3 -> check q2-4weeks
    • Months 3-6 -> check q8-12weeks
    • After 6 months -> check q12weeks
  • Baseline screen for HBV, HCV (and HIV) recommended in high risk px
  • Baseline chest x-ray
25
Q

Leflunomide for RA (category, appropriateness, efficacy, and safety)

A
  • Category -> synthetic oral DMARD
  • Appropriateness -> recommended in all guidelines as an alternative to MTX in those intolerant
  • Efficacy -> considered equally effective as MTX
  • Safety -> common SE = diarrhea, alopecia, rash, headache, hepatotoxicity
  • Teratogenic (category X)
  • Due to long t1/2, elimination protocol suggested in pregnancy (male or female) or if severe toxicity occurs
26
Q

Lefluonomide lab monitoring and dosing

A
  • CBC+, PLT, ALT, alk phos, albumin, sCr
  • Once daily dosing, more expensive than MTX
  • Dose -> 10-20 mg daily
27
Q

Hydroxychloroquine (HCQ) for RA (category, appropriateness, efficacy, and safety)

A
  • Category -> synthetic oral DMARD
  • Appropriateness -> recommended as monotherapy only for mild disease; usually used in combination
  • Efficacy -> least effective oral DMARD; onset = 2-6 months
  • Safety -> best tolerated DMARD
    • Common SE = rash, GI (cramps, diarrhea), headache
    • Unique SE = blurred vision or difficulty seeing at night (reversible upon d/c)
28
Q

HCQ lab monitoring

A
  • CBC+, PLT, ALT, alk phos, albumin, sCr (routine lab monitoring not needed after baseline)
  • Complete ophthalmologic exam at baseline then annually for high risk (> 60 y/o, retinal disease, liver disease)
    • q5years for those at low risk
  • Once or twice daily dosing; dose -> 200-300 mg BID, after 1-2 months may decrease to 200 mg OD-BID
29
Q

Sulfasalazine (SSZ) for RA (category, appropriateness, efficacy, onset, and safety)

A
  • Category -> synthetic oral DMARD
  • Appropriateness -> 2nd line tx if pt has CI to MTX; 1st line option when used in combination
  • Efficacy -> less active than MTX
  • Onset -> 2-3 months
  • Safety -> dose-limiting GI SE = N, anorexia, diarrhea, and rash
    • Titrate dose slowly for GI tolerability
    • Rare (serious) SE = hepatitis, leukopenia, and agranulocytosis
30
Q

SSZ lab monitoring and dosing

A
  • CBC+ PLT, ALT, alk phos, albumin, sCr
  • Contraindicated in sulfa allergy
  • BID-TID dosing needed
  • Dose = 500 mg BID, then increase to 1 g BID
31
Q

Other DMARDs used for RA

A
  • Azathioprine
  • Cyclosporine
  • Tacrolimus
  • Minocycline
  • Penicillamine
32
Q

Tofacitinib for RA (class, appropriateness, efficacy, safety, and dose)

A
  • Class -> janus kinase (JAK) inhibitor – decreases signaling by a number of cytokine and growth factor receptors
  • Appropriateness -> used as monotherapy or w/ MTX; role in RA yet to be determined
  • Efficacy -> studied in px w/ inadequate responses to MTX +/- other DMARDs; 40-60% of px have > 20% improvement in sx
  • Safety -> black box warnings for risk of serious infections; not approved for use w/ biologics or other stronger immunosuppressant DMARDs (azathioprine, cyclosporine)
  • Dose -> 5 mg po BID; very expensive & conditional coverage
33
Q

Oral glucocorticoids for RA (role and safety)

A
  • Role -> short-term use at initial diagnosis for sx control or during flares
    • More effective than NSAIDs
    • DMARD-type of effects (slowing of radiographic progression)
    • Generally, well tolerated at the usual RA dose of prednisone 5-10 mg OD (or equivalent)
    • Lowest effective dose should be used
  • Safety SE -> hyperglycemia and CNS effects (mild to moderate); insomnia, anxiety, irritability, GI irritation, HTN, infection
    • Long-term use = osteoporosis, glaucoma/cataracts, weight gain/fluid retention, increased infection risk
  • Currently only used for flares or in the beginning stages of the disease after diagnosis
  • Appropriate down titration needed to prevent disease flares
34
Q

Glucocorticoids monitoring

A
  • Hyperglycemia -> test blood glucose if DM at baseline and daily; every 3-6 months in others
  • CNS effects
  • BP and lipids q3-6months
35
Q

What are biologic DMARDs? How do they work?

A
  • Genetically engineered protein molecules
  • All biologics work by 1 of 3 mechanisms:
    1. Interfere w/ cytokine function and/or growth factor receptors
    2. Inhibit the “second signal” required for T-cell activation
    3. Deplete B cells
36
Q

Examples of anti-TNF agents

A
  • Infliximab (Remicade)
  • Etanercept (Enbrel)
  • Adalimumab (Humira)
  • Certolizumab pegol (Cimzia)
37
Q

Examples of T-cell activation inhibitors

A
  • Abatacept (Orencia)
  • Tocilizumab (Actemra)
  • Anakinra (Kineret) and canakinumab (Ilaris)
38
Q

Example of B cell depletor

A

Rituximab (Rituxan) – MAb against CD20

39
Q

Role of biologic DMARDs for RA

A
  • 30-50% of px have an inadequate response to DMARDs
  • All considered equal as per RCT data (except anakinra – inferior response rates compared w/ other biologics)
  • Onset = 1-4 weeks
  • All biologics have improved efficacy when used w/ MTX
  • Choice of agent depends on – pt preference regarding route of administration (IV infusion vs. SQ self-injection), frequency of administration, cost, and clinician experience
40
Q

Role of TNF-alpha inhibitors for RA

A
  • Biologics should be considered after 3-6 months of 2 DMARDs (1 being MTX) alone or in combination
  • 2012 ACR guidelines -> TNF-alpha listed as initial option for tx naïve px +/- MTX in high disease activity + poor prognosis
  • Efficacy compared to traditional oral DMARDs -> quickest onset, largest/best sx and joint structure outcomes; largest achievement of remission
  • Use biologics w/ MTX (more effective than biologic monotherapy; especially infliximab, never use as monotherapy!)
41
Q

Safety of TNF agents

A
  • Serious infections (bacterial sepsis, reactivation of latent TB, viral or fungal opportunistic pathogens) have been reported
  • All px receiving biologics must be monitored for S/S of infection
  • Must be withheld during active systemic infection
  • TB screening mandatory for all biologics
  • Avoid in px w/ recent hx (< 5 years) of malignancy
  • Rarely, may cause worsening of existing HF/or precipitate new onset HF (avoid in EF 50% or less, NYHA class 3 or 4)
  • Px w/ pre-existing demyelinating disorders (ex: MS) shouldn’t receive due to worsening of disease and sx
42
Q

Tapering or d/c RA therapy

A
  • Unclear
  • Significant risk for disease flares upon discontinuation of synthetic DMARD therapy (50% or greater)
  • Remission must first be stable/persistent for several months (12 months)
  • General principles:
    • Remove NSAIDs/GCs first
    • Remove least active drugs next
    • Typically want long-term maintenance dose of MTX indefinitely
  • If pt on biological:
    • Remove NSAIDs/GCs first
    • Watch for maintenance of remission
    • Try expanding interval between doses or reducing dose of biological and eventually d/c
43
Q

General monitoring for RA

A
  • Monitor disease activity every 1-3 months (every 6-12 months once goals are met)
  • Add or change DMARDs every 3-6 months
  • Titrating doses can occur rapidly q1-3months (ex: MTX)
  • Goal for effectiveness = remission
  • Low disease activity may be an appropriate goal for px w/ more severe, long-standing disease (or during the early/initial tx phase)
  • Radiographs -> hands and feet q6-12months or longer in more established disease
44
Q

Monitoring effectiveness in community practice for RA

A
  • RA clinical disease activity index
  • No lab work needed
  • Score 0 to 76
    • Remission = 2.8 or lower
    • Low disease activity = 10 or lower
    • Moderate disease activity = 22 or lower
    • High disease activity > 22
45
Q

Non-pharms for RA

A
  • Pt education and counselling
  • Rest, exercise
  • Physical therapy, occupational therapy
  • Nutrition and dietary therapy
  • Bone protection
  • CV risk reduction
  • Vaccinations
46
Q

Pt education about RA

A
  • Expected outcomes and response times
  • Self-monitoring for safety and efficacy
  • Importance of adherence to non-pharm and pharm therapy
  • Set goals w/ px (for all types of pain)