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Interleukin-1 (IL-1)
- promotes the activation of monocytes and macrophages
- Stimulates the release of cartilage matrix metalloproteinases from fibroblasts and chondrocytes
- metalloproteinases mediate the destruction of articular cartilage
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Interleukin-4 (IL-4)
- Produced by CD4+ type 2 helper cells and helps drive the differentiation and growth of B cells
- Inhibits the activation of type 1 helper T cells and decreses the production of IL-1 and TNF-α
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Interleukin-6 (IL-6)
- produced by T cells, macrophages, monocytes, and synovial fibroblasts
- induces profliferation of synovial fibroblasts
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Interleukin-10 (IL-10)
- anti-inflammatory cyokine produced by macrophages, monocytes, and both T and B cells
- dampens the inflammatory response by inhibiting production of IL-1 and TNF-α as well as proliferation of T cells
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4 Major Criteras for RA
- Joint involvement: (0-5 pts)
- assess the number and location of joints involved
- Serology: (0-3 pts)
- RF (rheumatoid factor) and ACPA (anticyclic citrullinated peptide antibody)
- Acute-phase reactants positive: (0-1 pts)
- ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein)
- Duration of symptoms: (0-1 pts)
- less than or more than 6 week duration
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Clinical presentatin of RA
- Symptoms: RA
- joint pain and stiffness >6 weeks duration
- experience fatigue, weakness low-grade fever, loss of appetite
- muscle pain and afternoon fatigue
- joint deformity seen late in disease
- Signs: RA
- tenderness w/warmth and swelling over affected joints involving hands and feet
- distribution of joint involvement is symmetrical
- rheumatoid nodules may be present
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Summary of Biologic Agents
- NOT first line therapy for RA
- use w/ methotrexate
- variable response
- TB testing prior to use
- No live vaccines
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Release of TNF from T cells results
- increase vascular permeability
- release of nitric oxide
- vasodilation
- increased platelet activation and adhesion
- local activation of vascular endothelium
- increased expression of adhesion molecules on endothelial blood vessels
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Methotrexate
- blocks purine & pyrimidine biosynthesis
- inhibits production of spermine & spermidine
- lowers intracellular glutathione conc
- inhibit AICAR enzyme leading to release of AMP/ or adenosine a potent anti-inflammatory mediator
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Methotrexate drug-drug interactions
- probenecid
- NSAIDs
- penicillin G
- *drugs inhibt methotrexate elimination
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Avoid Methotrexate if:
- chronic liver disease (cirrhsosis)
- immunodeficiency
- leukopenia
- thrombocytopenia
- preexisting blood disorders
- CrCl <40
- pregnant
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Avoid Leflunomide if:
- preexisting liver disease
- pregnant
- *leflunomide toxicity occurs: treat with cholestyramine
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Hydrochloroquine adverse effect
- benign corneal deposits
- blurred vision
- scotomas (absent vision)
- night blindness
- *due eye exam prior to use
- *6 months to take effect
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Sulfasalazine adverse effects
- GI: nausea, vomiting, diarrhea, anorexia
- *sula or aspirin allergy: AVOID
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Congestive heart failure AVOID:
- infliximab
- etanercept
- * Ejection Fraction (EF) < 40: AVOID etanercept & infliximab
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Dosing regimen Infliximab
- 1 week
- 2 week
- 6 week
- then every 8 weeks thereafter
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Etanacept adverse reactions
local injection-site reactions
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Infliximab adverse reactions
- fever
- chills
- pruritus
- rash
- anaphylactic (very uncommon)
- * treat w: apap, diphenydramine, corticosteroid
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Corticosteroid treatment in RA
- used in severe RA pts who initiate DMARD therapy for bridging purposes
- low dose is used for long term treatment of RA
- high doses are used to control flares of RA
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Pregnancy RA
- treat w: sulfazalaine, hydroxychloroquine
- AVOID: methotrexate, leflunomide
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