11 - Treatment Options for Rheumatoid Arthritis Flashcards
How do you diagnose RA
Clinical diagnosis
ACR/EULAR criteria
What are the 4 ACR/EULAR criteria
Joint involvement Serology Acute phase reactants Duration of symptoms need >6/10 for diagnosis
How do you manage RA
1) Pain relief
2) Modification of disease progression (ASAP)
3) Adjunct therapy
What is the pain relief given in RA
Same as OA
Analgesics
NSAIDs
COX-2 inhibitors
When should DMAR be given
within 3months of symptoms
Gold standard DMAR
Methotrexate
What combination of DMARDs would you give to a newly diagnosed RA patient
Methotrexate
at least one other DMARD
Short term glucocorticoids
What would you give to a newly diagnosed RA patient who is pregnant
DMARD monotherapy
What would you do with this patient
Recent-onset RA and receiving combination DMARD and satisfactory control
Cautiously reduce dosage to a level that still controls the disease
How long before the benefit of methotrexate is seen?
3-12 weeks
How often do you give methotrexate
Orally
once a week
in the same day (start with a higher dose and then decrease it when controlled)
MoA of methotrexate
Folic Acid antagonist
Limits DNA and RNA synthesis
Inhibits dihydrofolate reductase and thymidylate synthetase
Blocks the production of pro inflammatory cytokines
Side effects of methotrexate
Can cause liver problems
Can affect blood count
What is sulfasalazine
Combination of sulfapyridine and salicylate with an azo bond
How is sulfasalazine absorbed
Not well absorbed across the gut (<15%)
so metabolised by gut bacteria into 5-ASA which is better absorbed
What is the MoA of sulfasalazine
Not well understood
some think treats local gut inflammation which causes a knock on effect to help with joint inflammation
What else can sulfasalazine treat?
Ulcerative collitis
What is hydroxychloroquine
Anti-malarial drug
What is the MoA of hydroxychloroquine
Blocks toll like receptor 9
Decreases activation of dendritic cells
do not get interaction between dendritic and b cells
What is the side effect of hydroxychloroquine
Rash
What is leflunomide
Efficacy similar to methotrexate
Inhibits pyrimidine biosynthesis through inhibiting dihydroorate dehydrogenase to inhibit DNA and RNA synthesis
Examples of TNFa blockers
Etanercept
Infliximab
Adalimumab
Etanercept
Fusion protein human TNF receptor 2 and Fc human IgG1
Binds and stops TNFa from signalling
1-4 weeks for effect
Infliximab
Monoclonal antibody against TNFa
Against the mouse binding site of TNFa with the remaining human 75% IgG1
Days to weeks for effect
Adalimumab
Human TNFa monoclonal antibody
Binds TNFa both soluble
Interleukin 1 blockers
Anakinra
Canakinumab
Rilonacept
Anakinra
Human recombinant IL-1 receptor antagonist
Binds to IL-1R preventing IL-1 binding
Differs from IL-1 by addition of N-terminal methionine
(binds to IL-1R with same affinity as IL-1)
2-4 weeks to have an effect
Canakinumab
Human monoclonal antibody
targets IL1-B
trials for COPD and gout
Rilonacept
Dimeric fusion protein extracellular domain of IL1R1 and Fc human IgG1
Used more for acute gout
B cell monoclonal antibodies
Used if unresponsive to anti-TNFa
Rituximab
Rituximab
Chimeric monoclonal antibody against CD20 on the surface of B-cells
Destroys malignant and normal B-cells
effects after 3 months of infusions
Abatacept
Fusion protein IgG fused to extracellular domain of CTLA-4
Prevents 2nd signal being delivered to T cell
Betalacept
Anti-CD28, modulate T-cell signalling
Tocilizumab
Human monoclonal antibody against IL-6 receptor
given in combo with methotrexate
Neutralising Anti Drug Antibodies
directly interferes with the biological drugs ability to work
Non-neutralising Anti Drug Antibodies
May form immune complexes around injection site reducing drug concentration and pharmacokinetics
T CELL
Abatacept
Belatacept
