Inflammatory Arthritis Flashcards
Disease Modifying Anti-Rheum Drugs (DMARDs): Use, timeline, what is used for bridge?
- Used early to prevent irreversible damage, minimize toxicities ass. with NSAIDs and corticosteroids
- No immediate analgesic effects, controls symptoms over time to delay/stop progression
- NSAIDs used to bridge pain relief
Non-Biologic DMARDs: when to initiate therapy, what to start on
- Initiate therapy within 3 months
- Start MTX or leflunomide
- Milder RA: hydroxychloroquine or sulfasalazine
Biologic DMARDs: reserved for who, what do they start on
- Reserved for pts who don’t respond well to non-biologic DMARDs OR have mod-severe dz
- Used alone or combo with non-bio DMARDs
- Most pts start a TNF inhibitor
Step-up approach
- Initiate 1 non-biologic DMARD, add others if needed
- Bridge NSAIDs or corticosteroids
- Intra-articular steroids are an underused tx option
Step-down approach
- Can work faster, initiate 2-3 DMARDs, then step down when/if remission occurs
- NSAIDs or corticosteroids
Two common regimens
- Triple therapy: MTX + sulfasalazine + hydroxychloroquine
- Biologic therapy: MTX (or leflunomide) + TNF-alpha inhibitor
When there is an acute flare in a patient with RA or psoriatic arthritis, what must you rule out? Explain symptom presentation
- Rule out acute infectious arthritis (usually Staph aureus)
- Symptoms may be more subtle as pt is on immunosuppressants
- Pts should report fever, malaise, etc (increased risk of infection)
Leading cause of death in RA pts
CAD
What is the main goal of therapy in pts with inflammatory arthritis?
Hit em hard and fast
How far in advance should live viral vaccines should be given prior to DMARD therapy?
1 month
Methotrexate MOA, clinical indications
- MOA: Folate antimetabolite that inhibits DNA synthesis
- Uses: various tumors, RA, psoriasis/psoriatic arthritis
What should you supplement 24 hours after MTX dose to decrease ADRs?
Folate (5mg)
MTX clinical pearls
- Anchor drug for RA
- Takes 3-6 weeks to kick in
- Hold for sick pts in hospital due to aplastic crisis
MTX and pregnancy; how long should men and women wait before attempting to conceive?
- Teratogenic and abortifacient (need condom + something)
- Men should wait at least 3 months
- Women at least 6 months
MTX - bone marrow suppression reversed with? Who should we not give it to? Abstain from what?
- Leukovorin
- Don’t give to pts with eGFR <30mL/min
- Abstain from ETOH
MTX Drug Interactions
- Anti-folate drugs (TMP-SMX)
- Drugs that decrease renal function (NSAIDs) increase risk of toxicity)
- PPIs increase concentration of MTX -> increase risk of toxicity
- Other immunosuppressants
MTX ADRs
- Stomatitis
- GI intolerance
- Bone marrow suppressant (RA ass with lymphoma)
- LFT abnormalities -> hepatitis -> liver fibrosis***
- MTX lung
Leflunomide MOA, clinical indication
- Immunomodulatory agent that inhibits pyrimidine synthesis
- Use: main role for pt who responded to MTX but got toxicity from it
Leflunomide precautions
- Carcinogenic and teratogenic (CI during pregnancy)
- Take cholestyramine to bind/eliminate drug
Leflunomide ADRs
- Diarrhea***
- Reversible alopecia
- Bone marrow suppression
- LFT abnormalities
Hydroxychloroquine MOA, clinical indications, pregnancy?
- MOA: inhibits movement of neutrophils and chemotaxis of eosinophils
- Uses: SLE, RA
- Safe in pregnancy
Hydroxychloroquine monitoring, contraindications
- Monitoring: Ophtho exam baseline and q3-12 months after 5 years of therapy
- Anyone with hx of retinal or visual field abnormalities
Hydroxychloroquine ADRs
- Watch QT issues
- Hemolysis in G6PD deficiency pts
- Ophthalmic ADRs (blurred vision, retinal damage)
Sulfasalazine MOA, clinical indications, pregnancy?
- MOA: interferes with secretion by inhibiting prostaglandin synthesis
- Uses: RA (with MTX and hydroxychloroquine in triple therapy), IBD
- Safe in pregnancy
Sulfasalazine ADRs
- Common: GI intolerance, sulfa rash**
- Serious rxns rare: hepatitis, bone marrow suppression
- Other: lupus-like syndrome, hemolysis in G6PD deficiency pts (get a quant G6 prior to initiation)
JAK inhibitors
- Tofacitinib
- Baricitinib
- Upadacitinib
JAK Inhibitors MOA
-Janus kinase inhibitor -> JAK signaling is a critical step in hematopoiesis and immune activation
JAK inhibitors clinical pearls including who you should save it for, pregnancy, and pt ed
- Oral biologic DMARDs*
- Save for severe RA
- Pregnancy: use effective contraception while taking and for at least 4 weeks after last dose
- Pt ed: call if fever, rash, etc
JAK Inhibitors Drug Interactions
Should not be co-administered with other biologic agents or potent immunosuppressive drugs (Azathioprine or cyclosporine)
JAK Inhibitor ADR to know for exam
-Thromboembolic dz** (consider in DDX of VTE, AMI, thrombotic CVA eval)
Azathioprine and Cyclosporine Uses
-Pts with refractory RA or systemic involvement such as rheumatoid vasculitis
TNF inhibitors (first and second line)
- First line: Infliximab, Etanercept, Adalimumab
- Second line: Certolizumab, Golimumab
TNF inhibitors MOA, clinical indications
- Pro-inflammatory cytokine that binds TNF and blocks its activity
- Uses: moderate to severe RA**, others include psoriatic arthritis, IBD, ankylosing spondylitis, systemic JIA
What TNF inhibitor is not effective for tx of IBD?
Etanercept
TNF inhibitors plus what has synergistic beneficial effects?
MTX
What other things must be done prior to TNF inhibitor usage?
- Appropriate vaccinations
- Appropriate CA screenings
- TST or IGRA before starting therapy, yearly after
- Serologic testing for HIV/HBV/HCV
Precautions with TNF inhibitors
- Hx of CA or CNS demyelinating disorders like MS
- Can cause or worsen CHF
TNF inhibitor ADRs
- Common: injection site rxns, infusion rxns, URTIs, GI intolerance
- Serious: drug-induced lupus, bone marrow suppression, demyelinating disorders, increased risk of malignancies (lymphoma)
- Other serious: serious bacterial infections, TB reactivation or dissemination, invasive or disseminated fungal infections (histoplasmosis)
Is there any affect on overall mortality rates associated with opportunistic infections while using TNF inhibitors?
No
What other biologic DMARD has been approved for giant cell arteritis and systemic JIA?
IL-6 receptor antagonist (Tocilizumab)
Moderate to severe psoriatic arthritis, step 1 and 2? Other options?
- Step 1: MTX or leflunomide
- Step 2: TNF-alpha inhibitors
- Others: oral PDE4 inhibitors, IL-17A antagonists (Secukinumab), IL-12/23 antagonists (Ustekinumab), abatacept, JAK inhibitors
Presentation of systemic JIA
- Daily high fever
- Evanescent MP rash
- Inflammatory polyarthritis
- Complication includes macrophage activation syndrome
Mild-mod tx and mod/severe tx of sJIA
- Mild to mod: NSAID, Systemic glucocorticoid, or both
- Mod to severe: traditional DMARD used (MTX or TNF-inhibitors)
What type of toxicity is an important cause of morbidity in the sJIA pts?
Glucocorticoid toxicity
