Rheumatoid Arthritis and Disease Modifying Agents Flashcards
Rheumatoid Arthritis: Clinical Features
A chronic, autoimmune, inflammatory disease:
- joint swelling
- joint tenderness
- destruction of synovial joint (WBC attack synovium)
- severe disability
- premature mortality
Cytokines
TNF alpha
Interleukin-1 (IL-1)
IL-6
Cytokines effect
- Increased endothelial permeability to leukocytes
- Stimulate osteoclasts
- stimulate release of collagenase
- progressive, irreversible deformities in joints and functional impairment
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
- Slows disease progression and preserve structure/function of joints
- inhibits cytokines
- suppresses activity of lymphocytes
- biologic and non biologic
Adjunct Treatments
- NSAIDs (do not affect disease process, reduces pain and inflammation)
- Corticosteroids
Methotrexate MOA
- Reduced purine biosynthesis results in reduced DNA synthesis
- at low doses (RA), selectively inhibits cytokine production and the replication of T and B cells
Methotrexate Contraindication
pregnancy and breastfeeding (discontinue 3 months before conception)
Methotrexate ADEs
- Decreased immune response: myelosupression
- GI toxicity: nausea & mucosal ulcers
- Pulmonary toxicity
- Hepatic fibrosis (monitor LFTs)
- Thrombocytopenia
- mild alopecia
- ADD folic acid to decrease ADEs
Leflunomide MOA
Inhibits autoimmune T cell proliferation and production of autoantibodies
Leflunomide Contraindication
pregnancy and breastfeeding
Leflunomide ADEs
Diarrhea Steven's Johnson Rash Alopecia Hematologic toxicity Severe Hepatotoxicity
Sulfasalazine and pregnancy
Pregnancy Category B
Sulfasalazine ADEs
- GI effects
- Lupus like syndrome
- Headache, fever, rash
- Hepatotoxicity
- Avoid if documented sulfa allergy
What tests do we perform for Methotrexate, Leflunomide, Sulfasalazine
Check CBC, LFTs, SCr
Biologic DMARDs MOA
- Interfere with cytokine function, signal transduction or production
- inhibit the “second signal” required for T cell activation
- deplete B cells
- rapid onset of action
Biological DMARDs precaution
- Increased risk of infection by both bacterial pathogens and atypical fungal and opportunistic pathogens
- Ensure proper vaccination history
Tumor Necrosis Factor (TNF) inhibitors
Adalimumab Certolizumab Etanercept Golimumab Infliximab
Safety in Anti TNF DMARDs
- Increased susceptibility to infections
- New or worsening cases of heart failure
- increased risk of lymphoma
- Injection site reactions, arthralgia, rash, cough
Non Anti TNF: Anakinra
Use: less potent than TNF inhibitors-rarely used
ADE: avoid combo with other biologics- increased frequency of SAEs
Non Anti TNF: Rituximab
Use: eliminates B cells
ADE: Fatal infusion related reaction
Non Anti TNF: Abatacept
Use: controls “cross talk” between T cells
ADE: Avoid with anti-TNF biologics (increases risk of infections)
Non Anti TNF: Tocilizumab
Use: Antibody binds to IL-6 receptors
ADE: Severe infections, GI perforations, neutropenia, thrombocytopenia, LFT elevations, hyperlipidemia
Non Anti TNF: Sarilumab
Use: IL-6 antagonist
Kinase Inhibitors MOA
- Inhibits the activity of JAK enzyme at cytokine receptor, which reduces cytokine transmission signaling, which decreases
- Blocks actions of multiple but NOT ALL cytokines
