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
Kinase Inhibitors contraindication
Not used with other biologic DMARDs (infection)
Often used with methotrexate
Kinase inhibitors drugs
Tofacitinib
Baricitinib
ADEs of JAK inhibitors
Diarrhea Infections Reactivation of TB Risk of Malignancy Avoid live vaccines GI perforation Hyperlipidemia Anemia, neutropenia Hepatotoxicity Thrombosis
