17 - Rheumatoid Arthritis Flashcards
(108 cards)
1
Q
Describe RA
A
- chronic systemic autoimmune disease
- synovial inflammation - joint swelling, stiffness, tenderness
- leads to cartilage injury, bone erosions, and joint damage
- long-term disability
- affects ppl of all ages
2
Q
more common in _____
A
women
3
Q
What is RA associated with?
A
- reduced QOL
- disability
- decreased life expectancy
- increased risk of CV disease and CV mortality, lympoproliferative disease and depression
4
Q
If not treated appropriately, what can happen?
A
can result in joint destruction and severe disability that can disrupt multiple aspects of a patients life (physical and social impairment)
5
Q
Compare a healthy joint to RA joint
A
RA joint will have:
- inflamed tendon
- bone erosion
- hyperplastic synovium
- inflammatory cells
- thinning of cartilage
6
Q
Most patients with RA form antibodies called _____ ____
A
rheumatoid factors
7
Q
Briefly compare OA to RA
A
OA:
- later onset
- bigger joints
- wear and tear
- morning stiffness < 1 hour
- no systemic symptoms
RA:
- earlier onset
- smaller joints (hands, wrists)
- morning stiffness > 1 hour
- systemic symptoms common
8
Q
Risk factors for RA
A
- genetic predisposition
- exposure to unknown environmental factors
- age
- gender (women)
- obesity
- smoking
9
Q
There are two branches of the disease. Describe them.
A
- Early RA (ERA) is defined as patients with symptoms of less than 3 months duration.
- Established disease - patients have symptoms due to inflammation and/or joint damage.
10
Q
___% of people have cyclic-type of progressive disease course
A
80
11
Q
__% have mild disease
A
10
12
Q
___% have severe/aggressive disease
A
15
13
Q
Time to what is crucial? (2 things)
A
- diagnosis
- initiation of DMARD therapy
14
Q
What classifies an early diagnosis?
A
within 6 months of the onset of joint symptoms
15
Q
Joint damage begins within ___ years of symptoms
A
2
16
Q
Describe the criteria for diagnosing RA
A
Need more than or equal to 6 points for diagnosis of RA:
Joint involvement:
- 1 medium to large joint (0)
- 2-10 medium to large joints (1)
- 1-3 small joints (2)
- 4-10 small joints (3)
- More than 10 joints (at least 1 of them small) (5)
Serology:
- negative RF and negative anti-CCP (0)
- low positive RF or low positive anti-CCP (2)
- high positive RF or high positive anti-CCP (3)
Acute phase reactants:
- normal CRP and normal ESR (0)
- abnormal CRP or abnormal ESR (1)
Duration of symptoms:
- Less than 6 weeks (0)
- 6 weeks or more (1)
17
Q
What is RF and anti-CCP ?
A
RF = rheumatoid factors
Anti-CCP = anti cyclic citrullinated protein
18
Q
Symptoms of RA
A
- joint pain and stiffness > 6 weeks, stiffness lasts more than one hour
- 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
19
Q
Signs of RA
A
- joint involvement is frequently symmetrical
- tenderness and warmth and swelling over affect joints (usually hands and feet)
- systemic symptoms may be present
- rheumatoid nodules may also be present
20
Q
Describe the lab values in diagnosis
A
- Labs normal >30% of the time
- RF or anti-CCP (+) patients: worse prognosis
- RF detectable in 60-70% of patients
- Anti-CCP detectable in 50-85% (can be detected years before diagnosis)
- Acute phase reactants may also be elevated (not specific to rheumatic disease (CRP, erythrocyte sedimentation rate)
21
Q
What are some other diagnostic tests?
A
- Joint fluid aspiration may show increased WBC counts without infection, crystals.
- Joint radiographs may show periarticular osteoporosis, joint space narrowing, or erosions.
22
Q
What are goals of therapy?
A
- Fully control signs and symptoms of the disease and half radiographic progression and joint damage
- Obtain rapid clinical improvement with a goal of 50% improvement within 3 months and ideally clinical remission.
- Remission can be defined using multiple composite disease activity measures
- Treatment should alleviate pain, stiffness and fatigue; prevent any further joint damage and destruction; maintain physical function and work capacity; and maximize quality of life
23
Q
Describe the DAS28 score
A
- Number of swollen joints at 28 sites
- Number of tender joints at 28 sites
- Patient estimate of global status
- ESR or CRP value
- Score > 5.1 = high disease activity
- Score > 3.2 to > 5.1 = moderate disease activity
- Score 2.6 to <3.2 = low disease activity
- Score < 2.6 = remission
24
Q
Methotrexate:
What category ?
A
synthetic DMARD
25
Methotrexate:
Place in therapy?
Methotrexate is the preferred DMARD with respect to efficacy and safety and should be the first DMARD used in patients with RA unless contraindicated
26
Methotrexate:
Efficacy?
most effective traditional oral synthetic DMARD
27
Methotrexate:
Onset of action?
4-6 weeks in most patients
- effective for all levels of disease activity
- SQ MTX weekly is recommended for those who lose benefit over time
28
Methotrexate:
Dose ?
Titrated to a usual max dose of 25mg per week by rapid dose escalation
- given weekly
- dangerous to give once daily
29
Methotrexate:
Safety?
Best side effect to efficacy ratio of any other synthetic or biological DMARD
30
Methotrexate:
Common SE ?
stomatitis, nausea, diarrhea and possibly alopecia
*can decrease incidence of some SE by giving folic acid tab
31
Methotrexate:
What is recommended for GI intolerant patients?
SQ MTX weekly
32
Methotrexate:
Significant ___ consumption should be strictly avoided.
alcohol
33
Methotrexate:
Can it be given in pregnancy?
no - it is teratogenic
34
Almost all meds given in RA require ____ monitoring
lab
35
What needs to be monitored for methotrexate?
CBC, PLT, ALT, alk phos, albumin, sCr:
- Months 1-3: check q2-4 weeks
- Months 3-6: check q8-12 weeks
- After 6 months: check q12weeks
Baseline screen for HBV, HCV & HIV recommended in high risk patients (ppl with multiple partners, drug abuse, HCP)
Baseline chest x-ray: baseline measure in case pulmonary infiltrates & pneumonitis develop (rare)
36
Methotrexate:
_____ dosing
weekly
37
Initial ____ therapy with traditional DMARD should be considered for certain patients
combination
38
Methotrexate:
To reduce SE, give with ___ ____
folic acid (either 1 mg daily or 5 mg weekly) following the MTX dose can be useful in reducing MTX side effects
IF YOU'RE RECOMMENDING MTX, NEED TO MENTION FOLIC ACID
39
Leflunomide:
Category?
synthetic oral DMARD
40
Leflunomide:
Who is it recommended for?
recommended in all guidelines as an alternative to TMX in those intolerant
41
Leflunomide:
Efficacy ?
considered - equally effective as MTX
42
Leflunomide:
common SE
diarrhea, alopecia, rash, headache, hepatotoxicity
43
Leflunomide:
can be given in pregnancy ?
nope - teratogenic
44
Leflunomide:
Due to long ____, elimination protocol suggested in pregnancy (male or female) or if severe toxicity occurs
t 1/2
45
Leflunomide:
Lab monitoring?
CBC, PLT, ALT, alk phos, albumin, sCr
46
Leflunomide:
_____ dosing
daily
47
Leflunomide:
____ expensive than MTX
more
$130/month
48
Leflunomide:
What dose?
10-20 mg PO daily
49
Hydroxychloroquine (HCQ):
Category?
synthetic oral DMARD
50
Hydroxychloroquine (HCQ):
Who is it recommended for?
recommended as mono therapy only for mild disease; usually used in combination
51
Hydroxychloroquine (HCQ):
Efficacy?
least effective oral DMARD
52
Hydroxychloroquine (HCQ):
Onset?
2-6 months
53
Hydroxychloroquine (HCQ):
Safety?
best tolerated DMARD
54
Hydroxychloroquine (HCQ):
Most common SE
They are infrequent:
- rash
- GI (cramps, diarrhea)
- headache
Unique SE:
-blurred vision or difficulty seeing at night (reversible upon discontinuation)
- ocular toxicity is possible
- hemolysis possible in G6PD deficiency patients
55
Hydroxychloroquine (HCQ):
Lab monitoring ?
CBC, PLT, ALT, alk phos, albumin, sCr
*routien lab monitoring not needed after baseline
56
Hydroxychloroquine (HCQ):
What other type of exam needed at baseline then annually for high risk?
eye exam
high risk patients (age > 60, retinal disease, liver disease)
*patients at low risk can get eye exam every 5 years
57
Hydroxychloroquine (HCQ):
What type of dosing?
BID or OD
58
Hydroxychloroquine (HCQ):
Dose?
200-300mg twice daily; after 1-2 months may decrease to 200mg OD-BID
59
Sulfasalazine (SSZ):
Category ?
synthetic oral DMARD
60
Sulfasalazine (SSZ):
Place in therapy ?
2nd line Tx if patient has contraindication to MTX; 1st line option when used in combination
61
Sulfasalazine (SSZ):
Efficacy?
less active anti-RA drug than MTX (avoid as mono therapy in poor prognosis disease features)
62
Sulfasalazine (SSZ):
Onset?
2-3 months
63
Sulfasalazine (SSZ):
SE ?
Dose-limiting GI side effects:
- nausea
- anorexia
- diarrhea
- rash also common
64
Sulfasalazine (SSZ):
_____ dose slowly for GI tolerability
titrate
65
Sulfasalazine (SSZ):
What are some rare but serious SE?
hepatitis, leukopenia and agranulocytosis
hemolysis possible in G6PD deficiency pts
66
Sulfasalazine (SSZ):
What labs do we need to monitor ?
CBC, PLT, ALT, alk phos, albumin, sCr
67
Sulfasalazine (SSZ):
CI in ____ allergy
sulfa
68
Sulfasalazine (SSZ):
Dosing ?
BID-TID dosing need
69
Sulfasalazine (SSZ):
What is the dose ?
500 mg twice daily, then increase to 1 g twice daily
70
What are some other DMARDs?
- Azathioprene
- Cyclosporine
- Tacrolimus
- Gold salts
- Minocycline
- Penicillamine
71
Tofacitinib:
Class? How does it work?
- Janus kinase (JAK) inhibitor
| - Decreases signalling by a number of cytokine and growth factor receptors
72
Tofacitinib:
Place in therapy ?
- used as mono therapy or with MTX
| - role in RA therapy yet to be determined
73
Tofacitinib:
Efficacy ?
- Studied in patients with inadequate responses to MTX +/- other DMARDs
- 40-60% of patients have >20% improvement of symptoms
74
Tofacitinib:
Safety ?
- Black box warnings for risk of serious infections (similar to biologics); not approved for use with biologics or other stronger immunosuppressant DMARDs (azathioprine, cyclosporine)
- Abnormalities in liver enzymes and lipids reported
75
Tofacitinib:
Daily dosing?
5mg po BID
76
Tofacitinib:
Cost?
Very expensive and not covered.
$17,550/year
77
Describe monitoring for RA
- Monitoring effectiveness is a crucial aspect to RA therapy
- Monitoring of 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 every 1-3 months (ex. MTX)
78
Goals for effectiveness?
Remission
- Low disease activity may be an appropriate goal for patients with more severe, long-standing disease (or during the early/initial Tx phase)
- Radiographs: hands and feet every 6-12 months or longer in more established disease
79
What is the role of oral glucocorticoids?
Short-term use at initial diagnosis for symptom control or during flares
80
Oral glucocorticoids:
More effective than ____
NSAIDs
81
Oral glucocorticoids:
What types of effects?
DMARD-types of effects - slowing of radiographic progression
82
Oral glucocorticoids:
Generally well tolerated at the usual RA dose of prednisone _____ mg OD (or equiv)
5-10
83
Oral glucocorticoids:
____ effective dose should be used. (ex. < 10 mg daily)
Lowest
84
Oral glucocorticoids:
Larger doses have been used for ?
- initial bridging therapy
| - flares
85
Oral glucocorticoids:
SE
- hyperglycemia
- CNS effects (insomnia, anxiety, irritability)
- GI irritation
- impaired wound healing
- HTN
- lipids
- infection
86
Oral glucocorticoids:
Can cause what with long-term use?
- HPA-axis sup
- osteoporosis
- osteonecrosis
- glaucoma/cataracts
- weight gain/fluid retention
- increased infection risk
87
Oral glucocorticoids:
Appropriate ___ _____ needed to prevent disease flares
down titration
88
Glucocorticoids:
When is it appropriate to use intraarticular injection ?
can be used when 1 or a few joints are excessively swollen or tender compared with the other affected joints
89
Glucocorticoids:
How often can you do intraarticular injections?
can be done every 3 months (not more than 2-3 ing per joint/yr)
90
Glucocorticoids:
What do we need to monitor?
- Hyperglycemia
- Test BG if DM at baseline & daily; every 3-6 months in others
- CNS effects
- BP & lipids q3-6 months
91
Biologics:
All work by 1 of 3 mechanisms:
Describe them
- Interfere with cytokine function and/or growth factor receptors
- Inhibit the "second signal" required for T cell activation
- Deplete B cells
92
List some anti-TNF agents
- Infliximab (Remicade)
- Etanercept (Enbrel)
- Adalimumab (Humira) or Golimumab (Simponi)
- Certolizumab pegol (Cimzia)
93
Principle behind anti-TNF therapy?
- TNF alpha causes joint inflammation and degeneration so we are inhibiting that here
- given when a patient fails on DMARD
- these meds do not require lab monitoring but carry a small increased risk of infections
- before starting should be tested for presence of Tb
- if they get an infection while on biologics, they should stop biologic until infection is cured
- can't give live vaccine while on a biologic
- assess vaccine Hx before starting biologic (ex. may need shingles vaccine and can't give that once you start biologic)
94
List some biologics that inhibit T cell activation
- Abatacept (Orencia)
- Toclizumab (Actemra)
- Anakinra (Kineret) & Canakinumab (Ilaris)
*should be given with methotrexate
95
List a biologic that depletes B cells
- Rituximab
| * inhibits pro-inflammatory effects of B cells
96
Role of biologic DMARDs?
- 30-50% of patients have an inadequate response to DMARDs
- All considered equal as per RCT data
- Except anakinra: inferior response rates compared with other biologics
97
Biologic DMARDs:
Onset?
1-4 weeks
98
Biologic DMARDs:
All biologics have improved efficacy when used with ____
MTX
99
Biologic DMARDs:
Choice of agent depends on ?
Patient preference:
- Route of administration - IV vs SQ self injection
- Frequency of administration
- Cost
- Clinician experience
100
TNF-alpha inhibitors:
When should they be considered?
After 3-6 months of 2 DMARDS (1 being methotrexate) alone or in combination
101
TNF-alpha inhibitors:
When are they considered as an initial option?
in Tx naive patients +/- MTX in high disease activity + poor prognosis
102
TNF-alpha inhibitors:
Describe the efficacy of TNF-alpha inhibitors compared to oral DMARDs
- quickest onset
- largest/best symptom and joint structure outcomes
- largest achievement of remission
103
Use biologics with _____ = more effective than biologic mono therapy
*especiallly infliximab - never use as monotherapy
MTX
104
Biologics are Part __ EDS
3
105
Biologics should only be used in MTX naive patients if ?
Patient meets similar eligibility criteria of RCTs in this population:
- high/severe disease activity
- ESR > 20-30 mm/h
- bone erosions by radiograph or MRI
- positive anti-CCP or RF
- large number of affected joints (SJC & TJC)
106
Describe the safety of TNF agents
- Serious infections (bacterial sepsis, reactivation of latent TB, viral or fungal opportunistic pathogens) have been reported.
- All patients should be monitored for signs/symptoms of infection
- Must be withheld during active systemic infection
- Tb screening is mandatory for all biologics
- Risks of neoplasm (esp lymphomas); ongoing controversy, still not known if risk is due to drugs or RA itself
- Avoid use in patients with a recent history (<5 yr) of malignancy
- Rarely, may cause worsening of existing HF/or precipitate new onset HF
- Patients with pre-existing demyelinating disorders (ex. MS) should not receive due to worsening of disease and symptoms
107
How should we taper doses or DC therapy?
- Unclear
- Significant risk for disease flares upon discontinuation of synthetic DMARD therapy (>50%)
- Remission must first be stably/persistently achieved 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 patient on biological:
- Remove NSAIDs/GC first
- Watch for maintenance of remission
- Try expanding the interval between doses or reducing the dose of biological and eventually D/C
108
Non-pharms for RA
- patient education and counselling
- rest
- exercise
- physical therapy
- occupational therapy
- nutrition and dietary therapy
- bone protection
- CV risk reduction
- vaccinations
* quit smoking
* address high lipids or high BP
