23 - Rheumatoid Arthritis Flashcards
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
- 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
Leflunomide for RA (category, appropriateness, efficacy, and safety)
- 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
Lefluonomide lab monitoring and dosing
- CBC+, PLT, ALT, alk phos, albumin, sCr
- Once daily dosing, more expensive than MTX
- Dose -> 10-20 mg daily
27
Hydroxychloroquine (HCQ) for RA (category, appropriateness, efficacy, and safety)
- 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
HCQ lab monitoring
- 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
Sulfasalazine (SSZ) for RA (category, appropriateness, efficacy, onset, and safety)
- 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
SSZ lab monitoring and dosing
- 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
Other DMARDs used for RA
- Azathioprine
- Cyclosporine
- Tacrolimus
- Minocycline
- Penicillamine
32
Tofacitinib for RA (class, appropriateness, efficacy, safety, and dose)
- 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
Oral glucocorticoids for RA (role and safety)
- 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
Glucocorticoids monitoring
- Hyperglycemia -> test blood glucose if DM at baseline and daily; every 3-6 months in others
- CNS effects
- BP and lipids q3-6months
35
What are biologic DMARDs? How do they work?
- 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
Examples of anti-TNF agents
- Infliximab (Remicade)
- Etanercept (Enbrel)
- Adalimumab (Humira)
- Certolizumab pegol (Cimzia)
37
Examples of T-cell activation inhibitors
- Abatacept (Orencia)
- Tocilizumab (Actemra)
- Anakinra (Kineret) and canakinumab (Ilaris)
38
Example of B cell depletor
Rituximab (Rituxan) – MAb against CD20
39
Role of biologic DMARDs for RA
- 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
Role of TNF-alpha inhibitors for RA
- 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
Safety of TNF agents
- 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
Tapering or d/c RA therapy
- 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
General monitoring for RA
- 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
Monitoring effectiveness in community practice for RA
- 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
Non-pharms for RA
- Pt education and counselling
- Rest, exercise
- Physical therapy, occupational therapy
- Nutrition and dietary therapy
- Bone protection
- CV risk reduction
- Vaccinations
46
Pt education about RA
- 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)
