Outline the treatment pathway for rheumatoid arthritis.
Pain relief (analgesics, NSAIDs, COX-2 inhibitors) and then DMARDS (biological or non-biological)
What regions are most commonly affected by rheumatoid arthritis?
Small joints of the hands and feet
What is the difference in action of biologicals and non-biologicals in DMARDs?
Non-biologicals target the immune cells often by unknown mechanisms whereas biologicals target specific parts of the inflammatory cascade and are specific
Name some examples of non-biological DMARDs
Gold, sulfasalazine, methotrexate
Name some examples of biological DMARDs
Infliximab, adalimumab, rituximab
What is the initial treatment given for rheumatoid arthritis
In newly diagnosed patients they are prescribed methotrexate and at least one other DMARD plus short-term glucocorticoids (steroids)
What are the some of the issues associated with non-biological DMARDs?
Take a long time for them to start working
What are the potential side-effects of methotrexate?
Liver problems, affect blood count, folic acid antagonist
What is sulfasalazine?
This is a form of antibiotic that combined sulfapyridine and salicyclate with an azo bond that is used as a non-biological DMARD in the treatment of rheumatoid arthritis
Why can’t methotrexate be given to pregnant women?
It is a folic acid antagonist and therefore increases the risk of neural tube defects
How can hydroxychloroquine be used in the treatment of rheumatoid arthritis?
Antimalarial drug which accumulates in lysosomes to increase acidity and decrease protein modifications and block TLR-9 and decrease activation of dendritic cells.
How can leflunomide be used to treat rheumatoid arthritis?
Mode of action is poorly understood but though tot inhibit pyrimidine biosynthesis by inhibiting dihydroorotate dehydrogenase to prevent DNA and RNA synthesis.
How may azathioprine be used in the treatment of rheumatoid arthritis?
It’s a pro-drug consisting of 6-metcaptopurine and a purine synthesis inhibitor; it interferes with the synthesis of prints required for DNA synthesis. It can be used in combination with prednisolone to reduce the dose of steroid required.
How may gold salts be used in the treatment of rheumatoid arthritis?
Mechanism is poorly understood but can have substantial side-effects and take a long time to work.
Name three examples of TNFa inhibitors used in the treatment of rheumatoid arthritis
Etanercept, infliximab, adalimumab
Name three IL-1 inhibitors used in the treatment of rheumatoid arthritis
Anakinra, canakinumab, rilonacept
What targets are used for biological therapy for rheumatoid arthritis?
TNFa, IL-1, IL-6, B cells and T cells.
Name an IL-6 inhibitor used in the treatment of rheumatoid arthritis
Tocilizumab
Name a B cell inhibitor used in the treatment of rheumatoid arthritis
Rituximab
Name a T cell inhibitor used in the treatment of rheumatoid arthritis
Abatacept
Outline how etanercept works to treat rheumatoid arthritis
Combination of TNF receptor and Fc portion of human IgG1 which works to prevent TNFa from binding to it’s receptors and providing an inflammatory response
ESSENITALLY: antibody against TNFa
Outline how infliximab works to treat rheumatoid arthritis
This is a monoclonal antibody against TNFa
Outline how adalimumab works to treat rheumatoid arthritis
Human TNFa monoclonal antibody which can bind TNFa in soluble and insoluble forms to prevent binding to receptor
Outline how anakinra works to treat rheumatoid arthritis
This is a recombinant IL-1 receptors which binds to IL-1 also to block the receptor so IL-1 can’t bind to have an effect
Outline how canakinumab works to treat rheumatoid arthritis
Human monoclonal antibody which targets IL-1b to bind IL-1 before it gets to the receptor to work
Outline how rilonacept works to treat rheumatoid arthritis
Binds to extracellular domain of IL-R1 receptor and the Fc portion of human IgG1 to bind IL-1 before it can act on the receptors.
Outline how rituximab works to treat rheumatoid arthritis
Monoclonal antibody against CD20 receptor on B cells to destroy normal and malignant B cells.
Outline how abatacept works to treat rheumatoid arthritis
A fusion protein of IgG and CTLA4 which has an affinity for the CD28 receptor on the T cells, which prevents the second signal from being delivered
Outline how toclizumab works to treat rheumatoid arthritis
Monoclonal antibody against IL-6
What condition, aside from rheumatoid arthritis, is rilonacept used to treat?
Acute gout