Therapeutics Exam 4 (Rheumatoid Arthritis) Flashcards
Does rheumatoid arthritis have symmetrical join involvement?
Yes
What kind of disease is rheumatoid arthritis?
chronic, inflammatory
At what age does onset of rheumatoid arthritis typically occur?
30-50
What are the 2 genetic tests that can be conducted for RA?
Major Histocompatibility Complex (MHC) Typing
Human Lymphocyte Antigen (HLA)
How does joint destruction occur in RA?
The synovial membrane is infiltrated with inflammatory cells that release cytokines
-this leads to cell proliferation and death
A Pannus forms (inflamed proliferating synovia) and invades into healthy cartilage and bone which destroys the joint
*This is a systemic inflammatory disease with an inflammatory response
What does the progression of RA over time look like?
-Inflammation declines over the course of the disease
-Disability increases over the course of the disease as the bone erodes
A score of what regarding the diagnostic criteria is used to diagnose RA?
6 or more
What are the most commonly affected joints in RA?
*Hands (MCP and PIP joints)
Wrists
*Feet
How does the location of RA differentiate it from OA?
RA is more common in the hands and feet
OA is more common in the hips, knees, and hands
What are the extra-articular manifestations of RA?
-Rheumatoid nodules
-Vasculitis
-Pulmonary
-Ocular
-Cardiac
-Felty’s
*note that these cover about every system we have because this is a systemic inflammatory disease
Where are rheumatoid nodules most likely to appear?
Hands
Elbows
Forearms
pressure points
When do we want to intervene with rheumatoid nodules?
Only if the patient is symptomatic!
What is vasculitis?
Inflammation of small, superficial blood vessels
What is the biggest concern with vasculitis in RA?
Infarction could lead to Necrosis!
-also associated with stasis ulcers
What pulmonary effects can the inflammation from RA have?
-Pleural effusions
-Pulmonary fibrosis
-Nodules
Rare: interstitial pneumonitis or arteritis (inflammation of arteries and lungs)
What ocular effects can RA have?
Keratoconjunctivitis sicca
-itchy, dry eyes, + inflammation
-when these symptoms are present it is called “Sjogren’s syndrome”
What cardiac effects can RA have?
-Increased risk of CV mortality
-Pericarditis
-Conduction abnormalities
Rare: myocarditis
What is Felty’s syndrome?
Combination of 3 conditions:
-Splenomegaly
-Neutropenia
-RA
The lab value Erythrocyte Sedimentation Rate (ESR) can be used to diagnose RA, what level is used to diagnose?
Normal: 0-20
Elevated Diagnostic: >20
The lab value C-Reactive Protein (CRP) can be used to diagnose RA, what level is used to diagnose?
Normal: 0-0.5
Elevated Diagnostic: >0.05
*note that >10 can indicate bacterial infection
What is the hallmark diagnostic criteria for RA?
Rheumatoid Factor (RF)
-antibody specific for IgM
*not all patients with RA are RF+ but majority are
-reported as a titer and the higher the titer, the poorer the prognosis
What is a hallmark way to diagnose RA?
Radiographic changes
-joint space narrowing
-bone erosion
What are the adjunct treatments used in RA (never used alone)?
NSAIDs
Corticosteroids
What are the disease modifying agents in RA?
DMARDs
Biologic Agents (Anti-TNF)
Biologic Agents (Non-TNF)
*these cannot cure the disease but can prevent further progression
What is the role of NSAIDs in RA?
Reduce pain, swelling, and stiffness
*Do not alter disease progression (use in combo with disease modifying agents)
Which NSAIDs cannot be used in sulfa allergy?
Celebrex
Sulfasalazine
What is the role of corticosteroids in RA?
Anti-inflammatory + Immunosuppressive
*not monotherapy
*use in acute flares! and patients with extraarticular manifestations
-Bridge therapy: In combo with DMARD while waiting for onset of action
-Long term/Low dose: for advanced disease or difficult to treat cases
How do we dose corticosteroids in RA?
Physiological dose
Low Dose: <10mg/day prednisone
High Dose: 10mg/day - 60 mg/day
Short-Term: < 3 months of therapy
Injections:
Do not use > every 2-3 months
*What are the short-term adverse effects of corticosteroids?
Hyperglycemia
Gastritis
Mood Changes
Elevated BP
*What are the long-term adverse effects of corticosteroids?
Aseptic Necrosis
Cataracts
Obesity
Growth Failure
HPA suppression
Osteoporosis
What do we monitor with corticosteroids?
BP
Blood glucose (hyperglycemia)
What does DMARD stand for?
Disease Modifying Anti-Rheumatic Drug
What are the 3 main considerations with DMARDs?
-Will potentially decrease/prevent joint damage and preserve joint integrity
-Timing of initiation is critical (need to start immediately upon diagnosis)
-Onset of action is delayed (6 mo)
What are the 4 traditional DMARDs used?
Methotrexate**
Sulfasalazine
Leflunomide
Hydroxychloroquine
What is the DMARD of choice for RA treatment?
Methotrexate
How do we dose methotrexate?
7.5 mg per WEEK po or IM
*up to 15-20mg weekly
-dose taken once weekly
What are the adverse effects of methotrexate?
Bone marrow suppression*
-GI symptoms are what patients struggle with most-
N/V/D*
Stomatitis/Mucositis*
Hepatic (cirrhosis, hepatitis, fibrosis)
Pulmonary (pneumonitis, fibrosis)
Dermatitis (rash, urticaria, alopecia)
Teratogenic!
What can be done to reduce symptoms with methotrexate?
Give 1mg/day of folic acid
*especially for GI symptoms
When is methotrexate contraindicated?
-Pregnancy/ Nursing
-Chronic liver disease (EtOH abuse)
-Immunodeficiency
-Blood dyscrasias
-Pleural/Peritoneal effusions
-Leukopenia/Thrombocytopenia
-CrCl < 40
What is an important consideration with the DMARD Leflunomide?
It is a prodrug
It has a long half life (14-16 days) -toxicity precaution
How do we dose Leflunomide?
100 mg po x 3 days, the 20 mg daily
What are the adverse effects of leflunomide?
Teratogenic
Alopecia
Increased LFTs
Diarrhea + Rash
What do we monitor with leflunomide?
CBC
SCr
LFT
What are important considerations for the DMARD sulfasalazine?
-Prodrug
-DO NOT USE IN SULFA ALLERGY
How do we dose sulfasalazine?
500 mg po BID to TID
-can do 1 g 2-3 times daily
What are the adverse effects of sulfasalazine?
N/V/D, anorexia
Photosensitivity
-more but photo is the main one
What do we monitor with sulfasalazine?
CBC
SCr
LFT
What is the role of hydroxychloroquine in DMARD therapy?
-Used in combination or early therapy
-Less efficacious than others
What are the adverse effects of hydroxychloroquine?
Retinal Toxicity
-N/V/D
-Increase skin pigment, rash alopecia
What is a potential advantage to using hydroxychloroquine?
-No myelosuppression
-No hepatic or renal toxicity
What do we monitor with hydroxychloroquine?
Vision exam
What are the Biologic DMARDs used?
TNF Antagonists (The Neutralizers):
-Etanercept
-Infliximab
-Adalimumab
-Golimumab
-Certolizumab
What are the precautions for using TNF-antagonist DMARDs?
-Infection risk
-Do not use in combo with IL-1 inhibitors or t-cell co-stimulation modulators
BLACK BOX WARNING:
-Neurologic/Demyelinating disorders
-Malignancies
-Congestive heart failure
-Hepatitis B reactivation
*do not give live vaccines
What are the adverse effects of the neutralizers (Anti-TNF)?
-Headache
-Rash
-Infection risk
-Injection site reaction risk
-CHF exacerbation
-Malignancy risk
-Risk of demyelinating disease
True or False: If a patient fails one TNF-antagonist therapy they can still use another one
True, they inhibit TNF in different ways
***What is the role of Etanercept in therapy?
Monotherapy or Combination with methotrexate
***How do we dose Etanercept?
50mg SQ once weekly
*may be difficult for patients with joint issues to self inject
***Whit is the role of Infliximab in therapy?
Only to be used in combination with methotrexate
***How do we dose Infliximab?
IV at 0, 2, and 6 weeks
Then every 8 weeks
***What is the role of Adalimumab in therapy?
-For patients with inadequate response to one or more DMARDs
-Monotherapy or Combination
***How do we dose Adalimumab?
SC every other week
If monotherapy, can use weekly
***What is the role of Golimumab in therapy?
Moderate-Severe RA
Combination with methotrexate only
***What is the dosing of Golimumab?
SC once monthly
***What is the role of Certolizumab in therapy?
Moderate-Severe RA
Monotherapy or Combination with non-BRM DMARDs
***What is the dosing of Certolizumab?
SQ at 0, 2, 4 weeks
Then every 2 or 4 weeks
What is the IL-1 Receptor Antagonist biologic used for RA? (BMR/bDMARD)
Anakinra
***What is the role of Anakinra in therapy?
Moderate-Severe RA in patients who failed one or more DMARDs
Monotherapy or Combination
*not in combo with TNF agents or abatacept
***How is Anakinra dosed?
SC daily
*Renal adjustment: if CrCl<30, do every other day
What do we monitor with Anakinra?
neutrophil count
What is the Selective T-cell Co-stimulation Modulator used for RA? (BMR/bDMARD)
Abatacept
***What is the role of Abatacept in therapy?
Moderate-Severe RA
-Use if inadequate response to one or more other DMARDs
-Monotherapy or Combination with DMARD (not TNF-a inhibitors or IL-1 antagoists)
***How is abatacept dosed?
Weight-based
IV over 30 minutes
Dose at 0, 2, and 4 weeks then every 4 weeks
What are the warnings associated with Abatacept?
Do not use with TNF antagonists or IL-1 antagonists
Increased infection risk
No live vaccines
Caution in COPD
What are the IL-6 receptor inhibitor biologics used in RA treatment?
Tocilizumab
Sarilumab
What is the role of IL-6 receptor inhibitors in therapy?
Moderate-Severe RA after inadequate response to one or more DMARDs
Monotherapy or Combination with MTX or other DMARDs
How is Tocilizumab dosed?
IV infusion over one hour monthly
How is Sarilumab dosed?
SQ every 2 weeks
What warning is associated with IL-6 inhibitors?
BLACK BOX WARNING:
Infections
What adverse effect is unique to IL-6 inhibitors?
Lipid Abnormalities
What is the anti-CD20 antibody used for RA treatment?
Rituximab
What is the role of Rituximab in therapy?
Moderate-Severe RA
Pts with inadequate response to TNF antagonists
Combination with methotrexate
*last resort
How is Rituximab dosed?
Two 1g infusions separated by 2 weeks
-Can retreat every 6 months
*Must give methylprednisolone 30mins before each infusion to reduce reaction
For which drug must you give methylprednisolone 30 minutes before an infusion to reduce the infusion reaction?
Rituximab
What class of drugs is considered targeted synthetic DMARDs?
JAK inhibitors
What is the role of JAK inhibitors in therapy?
Moderate-Severe RA after inadequate response to TNF
Alone or Combination with methotrexate or another DMARD
*do not use in combo with biologic response modifiers, azathioprine, or cyclosporine
*Newest medications, not first-line but this may change
What are the warnings for JAK inhibitors?
CYP P450 interactions
Cardiovascular events
What are the benefits of combination therapy?
Leads to decreased dosages which minimizes adverse effects
Can produce dramatic disease slowing
