RA - Block 1 Flashcards
Women are ___ as more likely to develop RA?
twice
What is the leading cause of death in patients with RA?
CV disease
What type of disease is RA?
Chronic, progressive autoimmune disease that affects the body’s joints & synovium that is a common comorbid of autoimmune conditions
What are genetic factors of RA?
- Genetic polymorphisms
- Patiets with 1st degree relatives with RA
- Hypogonadism (low testosterone)
What are the nongenetic facotrs of RA?
- Smoking
- Coffee
- Obesity
- Occupational hazard (silica)
- Viral infection (Epstein-Barr)
What antibody to IgG has a strong corrleation with poor RA prognosis?
Rheumatoid factor (RF)
What is a common B cells inflammaotry cytokine associated with RA?
Tumor necrosis factor:
1. Induction of adhesion molecules to the endothelium
1. Boosting T cell proliferation & differentiation
1. Promoting cell migration
1. Regulating matrix modeling
What is the inflamed, fibrotic synovium observed in patients with RA?
Pannus
Inflammatory cytokines (i.e., IL-8, prostaglandins, VEGF) promote angiogenesis, which stimulates additional migration of innate & adaptive immune responses to the synovium resulting in?
Inflammation
Inflammatory cytokines can circulate in the bone tissue & promote osteoclast activity/differentiation, resulting in?
Bone destruction
Compare and contrast OA with RA?
What are the sx of RA?
- Joint involvement
- Extra-articular involvement
What are joint sx with RA?
- Bilatteral
- Warthm and swelling (+/- pain)
- Morning stiffness (≥30 min in duration)
- Sx ≥6 weeks
What are extra articular sx of RA?
- Fatigue
- Weakness
- Decreased mood
What is are the lab findings of RA?
- ESR and CRP (non-specifity inflammatory process)
- RF
- Anti-cyclic citrullinated peptide (anti-CCP) antibodies
What lab result is more specifc for RA in early stages?
Anti-cyclic citrullinated peptide (anti-CCP) antibodies
What are the radiographic presentations of RA?
- Soft tissue swelling
- Joint space narrowing
What is the criteria of scoring RA?
Total score of ≥ 6 out of 10 points -> meets diagnostic criteria for RA
Not all patients with RA may score > 6 on the initial assessment, but scores may progress over time.
What are Current ACR & EULAR guidelines for RA?
Treat-to-target approach
What is the overall goal of treating RA?
Disease remission
What is the tx approach for RA?
Under the supervision of rheumatologist:
1. Includes non-pharmacologic & pharmacologic therapies
2. Focused on reducing inflammation & symptoms (i.e., joint pain, stiffness)
3. Does not reverse previously established joint damage
4. Slows RA progression -> reducing irreversible joint damage, disability, while improving quality of life
Non-pharm tx for RA?
- Exercise
- Weight loss
- Referral to occupational and physical therapy
- Referral to psychiatry
- Referral to social work
- Comprehensive patient education
- Surgery
What are the pharm tx for RA?
- Traditional DMARDs (methotrexate, leflunomide, sulfasalazine, hydroxychloroquine)
- Biologic DMARDs (Anti-TNF, Non TNF biologics)
- Janus Kinase Inhibitors (tofacitinib, baricitinib, upadacitinib)
- Adjunt tx (NSAIDs, CS)
Methotrexate
CI, Counseling
1st line for DMARD in most patient
CI: Pregnancy, breastfeeding, alcoholism, chronic liver dx, blood dyscrasias
Counseling:
* folic acid supplementation
* Hepatitis B and C before starting tx
Leflunomide
CI, Monitoring, Counseling, OD
CI: pregnancy, severe hepatic impairment, concomitant teriflunomide therapy
Monitoring: TB & pregnancy screenings before starting therapy
Counseling:
* negative pregnancy test prior to starting therapy & use two (2) forms of birth control during therapy
* If pregnancy is desired, patient must wait 2 years after discontinuation or use an accelerated drug elimination procedure.
Accelerated drug elimination procedures:
* Cholestyramine 8g PO TID x 11 days; use 4g dose, if the 8g dose is not tolerated
* Activated charcoal suspension 50g PO every 12 hours x 11 days
Sulfasalazine
Warning, Counseling
Warning: caution in G6PD deficiency
Counseling:
* Folic acid supplementation
* yellow-orange coloration of skin or urine.
* glucose-6-phosphate dehydrogenase (G6PD) deficiency, due to the risk of hemolytic anemia.
Hydroxychloroquine
ADR
Retinal roxicity
What increases the risk of developing retinal tox from hydroxychloroquine?
- Doses > 5mg/kg/day based on ABW
- > 5 years of therapy
- History of renal or macular disease
- Concurrent tamoxifen therapy
What are the dosage forms Anti-TNF Inhibitors?
Intravenous (IV) — infliximab
Subcutaneous (SC) — etanercept, adalimumab, certolizumab pegol, golimumab
What are the dosing frequencies of Anti-TNF inhibiotrs?
- Etanercept — once weekly (OR) twice weekly
- Adalimumab — once every 2 weeks (OR) once weekly
- Certolizumab pegol — once every 2 weeks (OR) once monthly
- Golimumab — once monthly
- Infliximab — once every 4 – 8 weeks
Anti-TNF Inhibitors
Warning, Monitoring, CI, Administration
Warning: Avoid in HF
Monitoring: Before therapy initiation: tuberculosis (TB) and hepatitis B screening
* During therapy: signs of infection, CBC, LFTs, hepatitis B and TB screenings, symptoms of HF, malignancies, vital signs
*
CI: Do NOT administer with other biologic DMARDs or live vaccines
Admin:
* Do NOT shake medication or store in the freezer.
* Do NOT refrigerate again, once it reaches room temperature.
* Rotate injection sites
How should you administer infliximab tx?
Pre-medicate with antihistamines, acetaminophen, & corticosteroids to reduce risk of infusion reactions
Abatacept
Warning, Storage, Monitoring
Warning: Patients with COPD
* Do NOT administer with other biologic DMARDs or live vaccines.
Storage: Protect from light exposure, and do NOT shake the medication.
Monitoring: Screen high-risk patients for TB and Hepatitis B prior to starting therapy
Rituximab
BBW, Adminitoration, Monitoring, CI
BBW: Infusion related rx
Admin: Consider pre-treatment with acetaminophen, diphenhydramine, & corticosteroids to decrease risk of infusion reactions
Monitor: Screen high-risk patients for TB, Hepatitis B, and Hepatitis C before starting therapy.
CI: Do NOT administer with other biologic DMARDs or live vaccines.
Tocilizumab & Sarilumab
ADR, CI, Monitoring
ADR: elevated LDL & total cholesterol
CI:
* Do NOT administer with other biologic DMARDs or live vaccines.
* Do NOT use SC injections for IV infusions, due to polysorbate 80 in SC formulations of tocilizumab.
Monitor: Screen high-risk patients for TB and Hepatitis B before starting therapy
What are the trad DMARD?
methotrexate, leflunomide, sulfasalazine, hydroxychloroquine
What are the biologic DMARD?
IV
Anti-TNF biologics
* adalimumab, etanercept, certolizumab, golimumab, infliximab
Non-TNF biologics
* abatacept, tocilizumab, rituximab, sarilumab
What are the JAK inhibitors?
PO
tofacitinib, baricitinib, upadacitinib
JAK inhibitors
BBW, ADR, CI, Warning
BBW:
* serious infections
* malignancy, thrombosis
* increased risk of mortality in patients ≥ 50 years old with ≥ 1 CV risk factor treated at higher doses
ADR: GI perforations, Elevated BP and lipids
CI: Do NOT administer with biologic DMARDs, potent immunosuppressants, or live vaccines.
Warning: Use caution in Asian patients due to increased frequency of side effects
NSAIDs therapy of RA
Adjunct option to DMARD therapy for patients with RA:
1. Do NOT use as monotherapy!
2. Does NOT slow disease progression!
3. More rapid onset of action (vs. DMARDs) -> consider as “bridge therapy” for DMARDs
CS tx of RA?
Adjunct option at low-doses to DMARD therapy for patients with refractory RA disese:
1. Do NOT use as monotherapy!
2. Can slow disease progression
3. Consider as “bridge therapy” for DMARDs
What are the ACR guidelines for RA?
What are the EULAR guideline for RA?
For patient with poor prognostic factors:
1. High disease activity
1. Early joint damage
1. Positive RF or anti-CCP antibodies
1. Failure of > 2 traditional DMARDs
Reassess dosages & therapeutic responses every 3 months after initiating or changing therapies.
RA meds safe for pregnancy? CI?
Safe: hydroxychloroquine or sulfasalazine
* May continue TNF inhibitors, etanercept or certolizumab pegol, throughout pregnancy.
CI: Methotrexate and leflunomide
RA meds safe for lactation? CI?
Safe: hydroxychloroquine, sulfasalazine, corticosteroids, NSAIDs, & acetaminophen
CI: methotrexate and leflunomide
RA medications for men?
- Discontinue methotrexate 3 months before conception.
- Discontinue sulfasalazine if the patient experiences any difficulty with fertility
RA medications during hx of serious infection?
Recommended to use combination DMARDs, instead of TNF inhibitors
* Abatacept (non-TNF biologic) -> associated with lower risk of subsequent infections
What are the tx options based on TB screening results?
(+) TB: Obtain a chest x-ray to determine latent versus active TB.
(+) Chest X-ray: Obtain sputum for acid-fast bacillus (AFB) stain to rule out active TB.
(+) AFB stain: Diagnosis of active TB
* Complete treatment for active TB before initiating/resuming biologic DMARD or tofacitinib therapy.
(-) AFB stain: Diagnosis of latent TB
* Complete at least 1 month of treatment for latent TB, then initiate/resume biologic DMARD or tofacitinib therapy.
Tx for patients with previously treated lymphoproliferative disorders?
Rituximab -> FDA approved for lymphoproliferative disorders
Tx for patients with history of melanoma or non-melanoma skin cancer?
Traditional DMARDs
Tx option in patients with HF?
- Avoid TNF inhibitors in patients with NYHA class II – IV heart failure
- Discontinue TNF inhibitor if patient develops signs of worsening HF.
- Recommend alternative therapy (i.e., combination DMARDs, non-TNF biologic, or tofacitinib).
Live vaccines during RA?
Avoid use during treatment with biologic therapy.
Administer live vaccines prior to initiating biologic therapy (OR) at least 3 months after discontinuing
Inactivated vaccines for RA?
Can be administered to patients on traditional DMARDs, TNF biologics, non-TNF biologics, & JK inhibitors
Influenza vaccines for RA?
- Recommend annual IIV or RIV for patients with RA before starting/during therapy
- Recommend annual high-dose inactivated influenza vaccine (HD-IIV) for patients ≥ 65 years old with RA, regardless of concomitant RA therapy
Hep B for RA?
Administer as directed (per package insert), regardless of medications to treat RA
Tdap for RA
Recommend a booster dose of Td or Tdap vaccine once every 10 years.
Herpes zoster vaccine (RZV) for RA?
0 & 2-6 months after 1st dose
Patients receiving rituximab should receive a dose of RZV 4 weeks before next scheduled therapy.
Pneumococcal vaccines (PPSV-23, PCV-15, PCV-20) for RA?
Two inactivated vaccine types -> pneumococcal polysaccharide (PPSV) & pneumococcal conjugate (PCV)
