Rheumatoid Arthritis Flashcards
Erythrocyte Sedimentation Rate (ESR)
non specific
normal = 0 - 20 mm/hr
elevated in RA (> 20) = also elevated in general inflammatory disease
done routinely to see if meds are helpful or not or if there is a flare in the disease
C-reactive protein
non-specific
normal = 0 - 0.5 mg/dL
positive = > 0.5 mg/dL
> 10 mg/dL can indicate bacterial infection
done routinely to see if meds are helpful or not or if there is a flare in the disease
Rheumatoid factor (RF)
*hallmark diagnostic criteria (but false positives are possible)
antibody specific for IgM
not all patients with RA diagnosis are RF+ (pts can have a score of 6 or more w/out a positive RF test)
this is a dilution test that is reported as a titer (higher the titer can indicate more disease progression)
Anti-CCP/ACPA
relatively new (< 20 years its been around)
HIGH specificity
auto-antibody diagnostic test
present earlier in disease
predictive value for erosive disease
marker of poor prognosis
antinuclear antibodies (ANA)
less specific for RA –> still indicative for an autoimmune disease
elevated titer suggests autoimmune disease
more indicative of SLE (systemic lupus erythematosus)
reported as a titer (measurement of an amount or [ ] of a substance in a solution)
Joint aspiration
removing fluid from a space surrounding a joint to determine fluid contents
turbid = cloudy or muddy in appearance, less viscous than a normal joint space liquid (most likely due to elevated WBCs)
WBC: 5,000 - 50,000/mm^3
Glucose: normal to low compared to serum
Radiographic changes
class/hallmark way to diagnose RA
joint space narrowing
erosions of bone
Poor SOCIAL factors
low socioeconomic status
lack of formal education
psychological stress
poor Health Assessment Questionnaire (HAQ) scores
—is a quality of life score
Poor PHYSICAL factors
extra-articular factors (outside the joint space)
elevated ESR and CRP
high titers of RF
Elevated anti-CCP/ACPA
Erosions on X-Ray
Duration of disease
Swelling of > 20 joints
RA age of onset
any age
RA disease distribution
systemic involvement
RA ESR
elevated
RA inflammation
PRESENT
RA joint involvement
bilateral
SYMMETRIC
RA morning stiffness
> 1 hour
RA osteophyte
osteophyte = bony lumps that grow on the bones of the spine or around the joints
in RA, ABSENT
RA pannus
often PRESENT
RA Rheumatoid factor
frequently positive
RA subcutaneous nodules
frequently present
RA swelling
diffuse symmetric
RA typical presentation
malaise
fatigue
musculoskeletal pain
fever
RA has _________ w/ OA
VERY LITTLE
RA Tx Goals
improve/increase quality of life
reduce morbidity and mortality
alleviate S/Sx of disease
preserve fxn
prevent structural damage and deformity
control/avoid extra-articular manifestations
For RA, _____ _______ the damage that has already been done
CANNOT REVERSE
What is key w/ RA?
early tx to decrease disease severity
RA non-pharmacologic tx
education
emotional support
rest
weight reduction
physical therapy
heat
splints/prosthetics
surgery
RA pharmacologic tx
NSAIDs
corticosteroids
DMARDs (more specific to RA)
biologic agents anti-TNF
biologic agents non-TNF
NSAIDs & COX-2 Inhibitors Facts
Effective in reducing pain, swelling, and stiffness • Do NOT alter disease progression • Dose at anti inflammatory doses • Use in combination with DMARDs
NSAIDs & COX-2 Inhibitors cannot be used for…
…MONOTHERAPY
NSAIDs & COX-2 Inhibitors MOA
Inhibits COX and thus inhibits formation of
prostaglandins and inflammatory mediators
(involved in pain and inflammation)
Celecoxib (Celebrex) Dose + Caution
Dose: 100 200 mg by mouth twice daily
–
CAUTION with sulfa allergy
(know anti-inflammatory doses)
Don’t use Celecoxib (Celebrex) in patients with a…
SULFA ALLERGY
Corticosteroids
Used for anti inflammatory and immunosuppressive properties • Not used as monotherapy • Use in combination with DMARD • Use in acute flares • Use in patients with extra articular manifestations
want to use AS LITTLE as possible
Corticosteroids not used for…
…MONOTHERAPY
Use corticosteroids in patients with an…
ACUTE FLARE
Corticosteroids MOA
inhibit IL-1 production
NSAIDs and DMARDs have…
steroid sparing effects
Corticosteroid SHORT term effects
hyperglycemia
gastritis
mood changes
elevated BP
Corticosteroid LONG term effects
aseptic necrosis
cataracts
obesity
growth failure
HPA suppression
osteoporosis
DMARDs Facts
D isease M odifying A nti R heumatic D rugs • Potential to decrease/prevent joint damage & preserve joint integrity • Timing of initiation is critical • Onset of action is delayed
Methotrexate is the DMARD…
OF CHOICE
GOLD STANDARD
Methotrexate (MTX) Facts
Most predictable benefit • DMARD of choice • DMARD with best long term outcome • MOA: inhibit dihydrofolic acid reductase (inhibits neutrophil adhesion and chemotaxis)
Methotrexate Preferred administration
PO
Methotrexate Unique Dosing
7.5 mg PO PER WEEK
Methotrexate AE
Hematologic – Bone marrow suppression* • Gastrointestinal – N/V/D* – Stomatitis*/mucositis* • Hepatic – Cirrhosis – Hepatitis – Fibrosis
*= prescribe 1mg/day of folic acid to reduce symptoms
Pulmonary – Pneumonitis – Fibrosis • Dermatologic – Rash – Urticaria – Alopecia • Teratogenic (Wait one cycle on BCP // Wait 3 months before considering conception)
What are the worst methotrexate AE?
Gastrointestinal impacts = N/V/D
Decreases Pt Compliance
What should patients always have with methotrexate?
FOLIC ACID ( 1 mg/day) to reduce symptoms
What should women be taking while taking methotrexate?
Birth control if during child bearing age
MTX Contraindications
Pregnancy • Chronic liver disease (EtOH) • Immunodeficiency • Pre existing blood dyscrasias • Pleural/peritoneal effusions • Leukopenia/Thrombocytopenia • CrCL < 40 mL/min
Leflunomide (Arava) is a _________
pro-drug
Leflunomide (Arava) Patients need what?
Loading dose
Leflunomide T1/2
14 - 16 days
hepatobiliary clearance
Leflunomide AE
diarrhea
rash
alopecia
increased LFTs
teratogenicity
Sulfasalazine is a _______
pro-drug
Sulfasalazine MOA
inhibits IL-1
Which drugs should you be cautious using in sulfa allergy patients?
sulfasalazine and celecoxib
Sulfasalazine AE
Gastrointestinal – N/V/D, anorexia • Dermatologic – Rash/ Urticaria/ Photosensitivity • Hematologic – Leukopenia, thrombocytopenia – Rare: Hemolytic and aplastic anemia • Caution for allergy
Role of hydroxychloroquine?
Use in early or less aggressive disease
Advantage of hydroxychloroquine
its less efficacious but it DOES NOT have bone marrow suppression (myelosuppression)
Hydroxychloroquine unique AE
retinal toxicity (night/peripheral vision changes)
caution in elderly pts
need routine patients
inform patients take with food
Traditional DMARDs are…
conventional and ORAL agents
TNF Neutralizers (Biologic DMARDs)
Etanercept • Infliximab • Adalimumab • Golimumab • Certolizumab
Anti-TNFs should not be used in combination with other….
IL-1 inhibitors or T-cell co stimulation modulators
Anti-TNFs Warnings/Precautions
Risk of infection • Do not use in combination with IL 1 inhibitors or t cell co stimulation modulators • Black box warnings • Demyelinating disorders • Malignancies • Congestive heart failure • No concurrent live vaccination administration • TB skin test before start test
If using an anti-TNF, make sure the patient is not getting…
…a live vaccine
Anti-TNF AEs
Headaches and rash • Risk of infection (upper respiratory most common) • Injection site reaction • Exacerbations of CHF • Risk of malignancy • Risk of evidence of demyelinating disease
Etanercept (Enbrel) is used…
…monotherapy OR in combination with MTX
Infliximab (Remicade) has…
mouse and human portions to reduce antigenic potential
Infliximab (Remicade) Dosage Form
IV
Infliximab (Remicade) indicated to be used with…
MTX~!
Adalimumab (Humira) indicated
if pts had inadequate response to previous therapy
Adalimumab (Humira) can be used…
alone OR in combination
Golimumab (Simponi) used…
used in combination w/ MTX
Golimumab (Simponi) indicated
moderate to severe RA
Golimumab (Simponi) is a…
…human monoclonal antibody specific for TNF-alpha
Golimumab (Simponi) requires…
Laboratory monitoring:
CBC with PLT
LFTS
Certolizumab (Cimzia) can be used
alone OR in combination with non-BRM DMARDs
for moderate to severe disease
Anakinra (Kineret) can be used…
alone or with other agents (not anti-TNFs)
For Anakinra (Kineret)…[dosing]
can decrease the dose if CrCl < 30 ml/min
For Anakinra (Kineret) AE
Injection site reactions • Headache, N/V, flu like symptoms • Hypersensitivity to e.coli derived proteins • Increased risk of serious infections • Decreased neutrophils
For Anakinra, suggested to monitor
Neutrophil count: – Prior to start – Monthly for 3 months – Quarterly for up to one year
For Anakinra, its the only
IL-1 inhibitor
Abatacept (Orencia) indication
moderate to severe RA
Abatacept (Orencia) can be used
monotherapy or in combination
Abatacept (Orencia) warnings
Do not use with TNF antagonists or IL 1 antagonists • Increased risk of infection • No live vaccination administration • Caution in patients with COPD
Abatacept (Orencia) warnings
Headache • Nausea • Upper respiratory infection • Nasopharingitis • Infusion reactions • Serious infection • Malignancy
IL-6 inhibitors
tocilizumab (Actrema ®) and sarilumab (Kevzara ®)
IL-6 inhibitors indication
Moderate to severe RA after inadequate response to
one or more DMARDs
–
Alone or in combination with MTX or another
DMARD
IL-6 inhibitors warnings
Black box warning : serious infections
•
Contraindicated in patients with liver
toxicity, thrombocytopenia, and neutropenia
tocilizumab AE
Serious infection • Liver toxicity • Thrombocytopenia • Neutropenia • Lipid abnormalities • Intestinal perforations (tocilizumab) • Infusion reactions (tocilizumab)
Unique Tocilizumab AE
Lipid abnormalities
IL-6 inhibitors Monitoring Parameters
Neutrophil count at 4 8 weeks then every 3 months
•
Platelet count at 4 8 weeks then every 3 months
•
LFTS at 4 8 weeks then every 3 months
•
Lipid profile after 4 8 weeks then every 6 months
Rituximab (Rituxan) Indication
For moderate to severe RA – In those with inadequate response to TNF antagonists – In combination with MTX
Rituximab used…
in combination with MTX
Rituximab reserved…
…for those who failed or did not have adequate response to Anti-TNF
reserved for later in therapy
Rituximab AE
Tumor lysis syndrome • Mucocutaneous reactions • Viral infection • Hypersensitivity • Renal toxicity • Bowel obstruction • Hepatitis B reactivation • Cardiac arrhythmia
Tafacitinib (Xeljanz, XR) Indication
Moderate to severe RA after inadequate response to MTX
Tafacitinib (Xeljanz, XR) used…
Alone or in combination with MTX or another DMARD
Tafacitinib (Xeljanz, XR) NOT used…
Not in combination with BRM, azathioprine, or cyclosporine
Tafacitinib Warnings
Cytochrome P 450 interactions • Do not use in hepatic impairment • Risk of infection (Black box warning) • Risk of malignancy (Black box warning) • Do not use if: – Hemoglobin < 9 mg/dL – ANC < 1000 cells/mm 3 – ALC < 500 cells/mm 3
Tafacitinib AE
Upper respiratory – Headache – Diarrhea – Nasopharyngitis
Tafacitinib Monitoring Parameters
Lymphocyte count – Neutrophil count – Hemoglobin – Liver enzymes – Lipid profile
BARICITINIB (Olumiant ® ) indication
Moderate to severe RA after inadequate response to TNF
–
Alone or in combination with MTX or other DMARDs
–
Not in combination with BRM, azathioprine, or cyclosporine
In order to use BARICITINIB (Olumiant ® )…
must have failed a anti-TNF therapy
BARICITINIB WARNINGS
Do not use in severe hepatic impairment • Do not use if GFR < 60 ml/min • Risk of infection • Risk of malignancy • Risk of thrombosis • Do not use if: – Hemoglobin < 8 mg/dL – ANC < 1000 cells/mm 3 – ALC < 500 cells/mm 3
BARICITINIB AE
Upper respiratory – Nausea – Herpes simplex virus – Herpes zoster
BARICITINIB Monitoring Parameter
Lymphocyte count – Neutrophil count – Hemoglobin – Lipid profile – Liver enzymes
UPADACITINIB (Rinvoq®) Indication
Moderate to severe RA after inadequate response to MTX
UPADACITINIB (Rinvoq®) used…
Alone or in combination with MTX or another non biologic DMARD
UPADACITINIB (Rinvoq®) not used…
Not in combination with BRM, azathioprine, or cyclosporine
