Exam 4 lecture 4 Flashcards
Define rheumatoid artheritis
Chronic disease, involves symmetrical joint involvement, most common systemic inflammatory disease
epidemiology of RA
Occurs at any age. Usually between 30-50 yo.
shortens lifespan by 3-18 years
affects females more than males
How does RA happen
The disease involves the joint being invaded by inflammatory cells (macrophages, T cells and plasma cells). They release cytokines and leading to cell proliferation and death.
Pannus develops. Pannus is the development of inflammed synovium. It invades the bone and cartilage, leading to destruction of joint.
What are some prodromal effects patients with RA report
Fatigue, weakness
loss of appetite
Joint pain
Low grade fever
Stiffness + Muscle ache, Joint swelling
Diagnostic criteria for RA
joint involvement, Serology, duration of symptoms, acute phase reactants. Diagnosed with RA if there is a score of 6 or more.
Most common joints involved in RA
Wrists, hands and feet
May involve- elbow, knees, hip ankles
What are the most common joints in the hand with RA
Metacarpal and proximal interphalangeal joints are most common
What are some extraarticular manifestations of RA
Rheumatoid nodules
Vasculitis
Pulmonary
Ocular
Cardiac
Feltys
Where are rheumatoid nodules common?
Hands, elbow, forearms (pressure points)
usually asymptomatic
Define vascultits
Inflammation of small, superficial blood vessels
can lead to necrosis
Pulmonary effects of RA
Pleural effusions
Pulmonary fibrosis
Nodules
Interstitial pneumonitis
Ocular manifestations of RA
Keratoconjuctivitis Sicca
- itchy dry eyes + inflammation
Sjorgens syndrome (combo of inflammation in eye and itchy and dry eyes)
inflammation in sclera, episclera, cornea
cardiac manifestations of RA
Increased CV risk
Pericarditis
Conduction abnormalities
What is feltys syndrome
Splenomegaly and neutropenia in RA
What are some other manifestations of RA
Lymphadenopathy
Renal disease (associated with tx)
Thrombocytosis
Anemia
Lab indicators for patients with RA
Anemia
thrombocytosis (platelet counts may increase or decrease)
ESR (erythrocyte sedimentation rate )
CRP
RF (hall mark for RA)
Anti-CCP
ANA
Joint aspirations
Radiographic findings
What type of indicator is ESR (erythrocyte sedimentation rate)? What is normal? WHat is elevated/
Non-specific indicator
Normal- 0-20
Elevated>20
What is CRP level that may indicate RA? What value indicates bacterial infection?
> 0.5
> 10 may indicate bacterial infection
What is RF (rheumatoid factor)
Antibody specific for IgM.
Not all pts with RA are RF+ (60-70%)
What type of test is Anti-CCP
High specificity autoantibody presence test. Present in earlier disease and can be predictive for erosive disease. It is also a marker of poor prognosis
What are ANA in diagnosis of RA
Elevated titers suggest autoimmune disease. More indicative of SLE.
What does the joint aspiration of an RA patient look like
The fluid recovered from the joint is turbid (less viscous)
Turbidity due to WBC count.
Glucose normal to low compared to serum
What is the hallmark way to diagnose RA
radiographic changes (joint space narrowing and erosions of bone)
Tx goals of RA
improve/increase quality of life
Reduce morbidity and mortality
Alleviate signs and symptoms of disease
Preserve function
Prevents structural damage and deformity
control/avoid extra articular manifestations
non pharm treatment of RA
Education
Emotional support
Rest
Physical therapy
Heat
Splints/prosthetics
Surgery
Weight reduction
pharmacologic treatment of RA
NSAIDs
Corticosteroids
DMARDs
Biologic anti-TNFs
Biologic non-TNFs
Monoclonal antibody
Targeted synthetic DMARDs
can we reverse damae thats been done?
no, we only preserve function. Prevent damage early.
Which two drugs are never used alone for RA
NSAIDs and corticosteroids
Do NSAIDs alter disease progression? what is it effective for? What to combine it with? What doses should we use?
DO NOT alter disease progression
Use in combination with DMARDs.
effective in reducing pain, swelling and stiffness
Dose at anti inflammatory doses (remember doses for antiinflammation (they are higher))
Celecoxib should not be used for what patients
Patients with sulfa allergy
When are corticosteroids used? What is it combined with? Can it be used as monotherapy?
Used in patients with extra-articular manifestations and acute flares.
Used for antiinflammatory and immunosuppressive properties
Not used as monotherapy
Used in combination with DMARDs
What drugs have steroid sparing effects
NSAIDs and DMArDs
What are low doses of corticosteroids? High doses? duration?
low dose- <10 prednisone
high > 10-60
short term < 3 month of therapy (longer duration= poor prognosis)
Duration for intraarticular injections of corticosteroid? Dose?
do NOT use > every 2-3 months
Use 10-25 mg/inj of HC per joint
short term adverse effects of corticosteroids
Hyperglycemia
mood changes
Elevated BP
Gastritis
Long term adverse effects of corticosteroids
Asceptic necrosis
Cataracts
Obesity
Growth failure
Osteoporosis
monitoring parameters for corticosteroids
BP every 3-6 months
BG every 3-6 months
What are the 3 different types of DMARDs
Traditional DMARDs (conventional synthetic DMARDs)
Biologic response modifiers (biologic DMARDs)
Targeted synthetic DMARDs
What does DMARDs stand for? What does it do? Onset?
Disease modifying anti rheumatic drugs
Potential to decrease/prevent joint damage and preserve joint integrity
Timing of initiation is critical
Onset of action is delayed
What are some conventional DMARDs drugs
Methotrexate (MTX)
Sulfasalazine (SSZ)
Hydroxychloroquine (HCQ)
Leflunomide
what is the gold standard of RA treatment
Methotrexate
(ost predicatble benefit, best long term outcome)
MOA of methotrexate
inhibits dihydrofolic acid reductase (inhibits neutrophil adhesion and chemotaxis)
dosing of methotrexate (exam)? onset?
2.5 mg tablets
start at 7.5 mg per week by mouth or IM
at 4-6 weeks titrate to 15 mg per week, you can go as high as 20 mg per week
Onset- 1-2 months
Methotrexate adverse effects
Gastrointestinal side effects (N/V/D) biggest issue with pts
stomatitis/mucositis (NEED TO TAKE WITH 1 mg FOLIC ACID SUPPLEMENT DAILY)
Hepatic
-cirrhosis
-hepatitis
- fibrosis
pulmonary
-pneumonitis
-fibrosis
Dermatologic
-rash
Urticaria
Alopecia
Teratogenic
- wait one cycle on BCP
Wait 3 months before considering conceotion
MTX contraindications
pre existing liver dysfunction (etOH abuse or chronic disease)
pregnancy
pre existing blood dyscrasias
pleural/peritoneal effusions
Crcl<40
immunodeficiency
leukopenia/thrombocytopenia
MTX monitoring
baseline
CXR
CBC
SCr
LFTs
Albumin
Maintenance (CBC, SCr, LFT)
<3 months- 2-4 wks
3-6 months- 8-12 wks
>6 months- 12 wks
What type of drug is leflunomide? half life?
It is a prodrug that requires loading dose
14-16 days
leflunomide adverse effects
Teratogenicity
Alopecia
Increased LFTs
Rash
Diarrhea
LEF (leflunomide) monitoring
CBC, SCr, LFT
<3 mo: 2-4 wks
3-6 mo : 8-12 wks
>6 mo: 12 wks
Sulfasalazine (SSZ) adverse effects? Is it a prodrug? Allergies?
gastrointestinal
- N/V/D, anorexia
Dermatologic
- rash/urticaria/photosensitivity
Hematologic
-leukopenia, thrombocytopenia
yes it is a prodrug
Not for pts with sulfa allergy
monitoring for SSZ
Same as Lef and MTX
what are advantages of hydroxychloroquin? unique Advrse effects of HCQ? monitoring HCQ?
Advantage- no myelosuppression, only renal and hepatic
Ocular toxicity is unique to HCQ (retinal toxicity)
GI (N/V/D)
Vision exam every 6-12 months
Mildest effectiveness, mildest adverse effects,
What are some biologic response modifiers (biologic DMARDs)
TNF neutralizers
IL1
IL6
Cosal stimulators
Whatare some TNF neutralizers? MOA?
Infliximab
Golimumab
certolizumab
adalimumab
Etanercept
Inhibit TNF, all in different ways. We can switch therapies within class
TNF neutralizers warnings/precautions? Blackbox?
increase risk of infection
DO NOT USE IN COMBO with IL-1 or t cell co stimulatory modulators or other biologics
blackbox warning-
Increase neurologic/demyelinating disorders
Malignancies
COngestive F
Hepatitis B reactivation
No concurrent live vaccine administration
TNF neutralizer adverse effects
Headache/ rash
Risk of infection (upper respiratory common)
inj site rxn
CHF exacerbation
Malignancy
Demyelinating disease
ROA of etanercept? ROA of
sq
Is infliximab a monotherapy forRA?
No, indicated in combo with MTX
What is adalimumab indicated in? Monotgherapy of combo?
Patients with inadequate response to one or more DMARDs
Both monotherapy and combo
ROA of adalimumab
Sc
golimumab indication? monotherapy or combo?
Used in moderate to severe RA
Used in combo with MTX
monitoring parameters for golimumab
CBC and PLT
LFTs
Certolizumab indication? Monotherapy or combo? ROA
RA patients with moderate to severe disease
can bealone or in combo with non-BRM DMARDS
ROA- Only IV is infliximab all others are SQ including this
What are some additional BRM BDMARDS
Anakinra- IL-1 inhibitor
Anakinra indication? Alone or n combination? MOA? ROA?
Moderate to severe RA in pts who have failed one or more DMARDS
Alone or in combination
IL-1 inhibitor
SQ
adverse effects of Anakinra? Monitoring?
Inj site rxn
H/a, N/v, flu like sc
HS to e coli derive dproteins
Decreasd neytrophils
reduce dose for CrCl<30
Monitor- neutrophl count monthly for 3 months
Name a selective T cell costimulation moduylator
Abatacept
Abatacept indication? monotherapy or combination?
moderate to severe RA use if inadequate response to on or more DMARDs
Monotheraoy or combination with DMARD
Can we combine Abatacept with TNF inhibitors or IL-1 antagonists
No
do we use biologic response modifiers in combination?
No
TNF, IL-1 co t cell stimulators. When we say combination we are thinking of mtx and all those.
ROA of abatacept
IV
Name IL-6 inhibitors? Indication? Alone or in combo? ROA?
Tocilizumab and sarilumab
Indication- moderate to severe RA after inadequate response to one or more MDARDs
Alone OR in combination with MTX or another DMARD
IV- tocilizumab
SQ- sarilumab
Blackbox warning of IL-6? CI?
serious infection
contraindicated in pts with liver toxicity, thrombocytopenia and neutropenia
Adverse effects of IL-6 inhibitors (Unique abnormalities)
Lipid abnormalities (unique)
serious infection
Liver
Blood dysgratias
Thrombocytopenia
Intestinal perforations/infusion rxn (tocilizumab)
Monitoring IL-6 inhibitors
Neutrophil count, platelet count, LFTs, Lipid profiler
Name an Anti-CD 20 antibody
Rituximab
Indication of rotuximab? monotherapy or combination? ROA? What is unique about giving rituximab?
Moderate/severe RA
Used in inadequate response to TNF antagonist
Used in combo with MTX
IV infusion (administer methylprednisone before infusion tor educe adverse effects) (Unique)
Adverse effects rituximab. Monitoring?
Every adverse affect
Monitoring
CBC, SCr, vitals during infusions
Name targeted synthetic DMARDs *
Janus kinase inhibitors
Indication for Janus kinase inhibitors? ALon eor combo? ROA?
Moderate to severe RA after inadequate response to TNF
Alone or in combo with MTX or another DMARD (not with biologic response modifier)
Oral (Unique)
Name the JAK inhibitors
Tofactinib
Barictinib
Upadactinib
Drug i/a of JAK inhibitors
Cytochrome P 450 i/a
Adverse effects of JAK inhibitors
DO not use in hepatic impairment
Risk of infection
Risk of malignancy
Major adverse CV events
Thrombosis
GI perforations
No live vaccines
Upper respiratory
H/A
Nausea
Which labs make use ignore JAK inhibitors as an option
Hemoglobin- <9
ANC<1000
ALC<500
Monitoring parameters of JAK inhibitors
lymphocyte count
Neutrophil count
Hemoglobin
Liver enzymes
Lipid profile (Unique along with Il-6)
Which two classes have lipid profile monitoring
JAK inhibitors and IL-6 inhibitors
if we have a clinical diagnosis of RA, what do we do 1st
Phase I- Start methotrexate (Leflunomide or sulfasalazine if contraindicated to methotrexate)
combine with short term glucocorticoids
What do we do if we do not see improval after 3 months or aulure to achieve target at 6 months
Phase II discontinue and try another therapy
If poor prognosis factors present- Add a bDMARD or JAK inhibitor
If poor prognosis factors absent
change to or add a second conventional synthetic DMARD (leflunomide, sulfasalazine or csDMARD combination (plus glucocorticoid)
What if still no response to phase II
Change to bDMARD or a JAK inhibitor
