17 - Rheumatoid Arthritis Flashcards
Describe RA
- 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
more common in _____
women
What is RA associated with?
- reduced QOL
- disability
- decreased life expectancy
- increased risk of CV disease and CV mortality, lympoproliferative disease and depression
If not treated appropriately, what can happen?
can result in joint destruction and severe disability that can disrupt multiple aspects of a patients life (physical and social impairment)
Compare a healthy joint to RA joint
RA joint will have:
- inflamed tendon
- bone erosion
- hyperplastic synovium
- inflammatory cells
- thinning of cartilage
Most patients with RA form antibodies called _____ ____
rheumatoid factors
Briefly compare OA to RA
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
Risk factors for RA
- genetic predisposition
- exposure to unknown environmental factors
- age
- gender (women)
- obesity
- smoking
There are two branches of the disease. Describe them.
- 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.
___% of people have cyclic-type of progressive disease course
80
__% have mild disease
10
___% have severe/aggressive disease
15
Time to what is crucial? (2 things)
- diagnosis
- initiation of DMARD therapy
What classifies an early diagnosis?
within 6 months of the onset of joint symptoms
Joint damage begins within ___ years of symptoms
2
Describe the criteria for diagnosing RA
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)
What is RF and anti-CCP ?
RF = rheumatoid factors
Anti-CCP = anti cyclic citrullinated protein
Symptoms of RA
- 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
Signs of RA
- 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
Describe the lab values in diagnosis
- 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)
What are some other diagnostic tests?
- Joint fluid aspiration may show increased WBC counts without infection, crystals.
- Joint radiographs may show periarticular osteoporosis, joint space narrowing, or erosions.
What are goals of therapy?
- 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
Describe the DAS28 score
- 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
Methotrexate:
What category ?
synthetic DMARD
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
Methotrexate:
Efficacy?
most effective traditional oral synthetic DMARD
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
Methotrexate:
Dose ?
Titrated to a usual max dose of 25mg per week by rapid dose escalation
- given weekly
- dangerous to give once daily
Methotrexate:
Safety?
Best side effect to efficacy ratio of any other synthetic or biological DMARD
Methotrexate:
Common SE ?
stomatitis, nausea, diarrhea and possibly alopecia
*can decrease incidence of some SE by giving folic acid tab
Methotrexate:
What is recommended for GI intolerant patients?
SQ MTX weekly
Methotrexate:
Significant ___ consumption should be strictly avoided.
alcohol
Methotrexate:
Can it be given in pregnancy?
no - it is teratogenic
Almost all meds given in RA require ____ monitoring
lab
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)
Methotrexate:
_____ dosing
weekly
Initial ____ therapy with traditional DMARD should be considered for certain patients
combination
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
Leflunomide:
Category?
synthetic oral DMARD
Leflunomide:
Who is it recommended for?
recommended in all guidelines as an alternative to TMX in those intolerant
Leflunomide:
Efficacy ?
considered - equally effective as MTX
Leflunomide:
common SE
diarrhea, alopecia, rash, headache, hepatotoxicity
Leflunomide:
can be given in pregnancy ?
nope - teratogenic
Leflunomide:
Due to long ____, elimination protocol suggested in pregnancy (male or female) or if severe toxicity occurs
t 1/2
Leflunomide:
Lab monitoring?
CBC, PLT, ALT, alk phos, albumin, sCr
Leflunomide:
_____ dosing
daily
Leflunomide:
____ expensive than MTX
more
$130/month
Leflunomide:
What dose?
10-20 mg PO daily
Hydroxychloroquine (HCQ):
Category?
synthetic oral DMARD
Hydroxychloroquine (HCQ):
Who is it recommended for?
recommended as mono therapy only for mild disease; usually used in combination
Hydroxychloroquine (HCQ):
Efficacy?
least effective oral DMARD
Hydroxychloroquine (HCQ):
Onset?
2-6 months
Hydroxychloroquine (HCQ):
Safety?
best tolerated DMARD
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
Hydroxychloroquine (HCQ):
Lab monitoring ?
CBC, PLT, ALT, alk phos, albumin, sCr
*routien lab monitoring not needed after baseline
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
Hydroxychloroquine (HCQ):
What type of dosing?
BID or OD
Hydroxychloroquine (HCQ):
Dose?
200-300mg twice daily; after 1-2 months may decrease to 200mg OD-BID
Sulfasalazine (SSZ):
Category ?
synthetic oral DMARD
Sulfasalazine (SSZ):
Place in therapy ?
2nd line Tx if patient has contraindication to MTX; 1st line option when used in combination
Sulfasalazine (SSZ):
Efficacy?
less active anti-RA drug than MTX (avoid as mono therapy in poor prognosis disease features)
Sulfasalazine (SSZ):
Onset?
2-3 months
Sulfasalazine (SSZ):
SE ?
Dose-limiting GI side effects:
- nausea
- anorexia
- diarrhea
- rash also common
Sulfasalazine (SSZ):
_____ dose slowly for GI tolerability
titrate
Sulfasalazine (SSZ):
What are some rare but serious SE?
hepatitis, leukopenia and agranulocytosis
hemolysis possible in G6PD deficiency pts
Sulfasalazine (SSZ):
What labs do we need to monitor ?
CBC, PLT, ALT, alk phos, albumin, sCr
Sulfasalazine (SSZ):
CI in ____ allergy
sulfa
Sulfasalazine (SSZ):
Dosing ?
BID-TID dosing need
Sulfasalazine (SSZ):
What is the dose ?
500 mg twice daily, then increase to 1 g twice daily
What are some other DMARDs?
- Azathioprene
- Cyclosporine
- Tacrolimus
- Gold salts
- Minocycline
- Penicillamine
Tofacitinib:
Class? How does it work?
- Janus kinase (JAK) inhibitor
- Decreases signalling by a number of cytokine and growth factor receptors
Tofacitinib:
Place in therapy ?
- used as mono therapy or with MTX
- role in RA therapy yet to be determined
Tofacitinib:
Efficacy ?
- Studied in patients with inadequate responses to MTX +/- other DMARDs
- 40-60% of patients have >20% improvement of symptoms
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
Tofacitinib:
Daily dosing?
5mg po BID
Tofacitinib:
Cost?
Very expensive and not covered.
$17,550/year
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)
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
What is the role of oral glucocorticoids?
Short-term use at initial diagnosis for symptom control or during flares
Oral glucocorticoids:
More effective than ____
NSAIDs
Oral glucocorticoids:
What types of effects?
DMARD-types of effects - slowing of radiographic progression
Oral glucocorticoids:
Generally well tolerated at the usual RA dose of prednisone _____ mg OD (or equiv)
5-10
Oral glucocorticoids:
____ effective dose should be used. (ex. < 10 mg daily)
Lowest
Oral glucocorticoids:
Larger doses have been used for ?
- initial bridging therapy
- flares
Oral glucocorticoids:
SE
- hyperglycemia
- CNS effects (insomnia, anxiety, irritability)
- GI irritation
- impaired wound healing
- HTN
- lipids
- infection
Oral glucocorticoids:
Can cause what with long-term use?
- HPA-axis sup
- osteoporosis
- osteonecrosis
- glaucoma/cataracts
- weight gain/fluid retention
- increased infection risk
Oral glucocorticoids:
Appropriate ___ _____ needed to prevent disease flares
down titration
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
Glucocorticoids:
How often can you do intraarticular injections?
can be done every 3 months (not more than 2-3 ing per joint/yr)
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
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
List some anti-TNF agents
- Infliximab (Remicade)
- Etanercept (Enbrel)
- Adalimumab (Humira) or Golimumab (Simponi)
- Certolizumab pegol (Cimzia)
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)
List some biologics that inhibit T cell activation
- Abatacept (Orencia)
- Toclizumab (Actemra)
- Anakinra (Kineret) & Canakinumab (Ilaris)
*should be given with methotrexate
List a biologic that depletes B cells
- Rituximab
* inhibits pro-inflammatory effects of B cells
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
Biologic DMARDs:
Onset?
1-4 weeks
Biologic DMARDs:
All biologics have improved efficacy when used with ____
MTX
Biologic DMARDs:
Choice of agent depends on ?
Patient preference:
- Route of administration - IV vs SQ self injection
- Frequency of administration
- Cost
- Clinician experience
TNF-alpha inhibitors:
When should they be considered?
After 3-6 months of 2 DMARDS (1 being methotrexate) alone or in combination
TNF-alpha inhibitors:
When are they considered as an initial option?
in Tx naive patients +/- MTX in high disease activity + poor prognosis
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
Use biologics with _____ = more effective than biologic mono therapy
*especiallly infliximab - never use as monotherapy
MTX
Biologics are Part __ EDS
3
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)
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
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
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
