Biologics Flashcards
What do T-cells do
- activate macrophages - release TNFa, IL-6, IL-1
- activate B-cells - release IL-6
all these cytokines activate osteoclasts to remove bone
Which is the most important cytokine RA
TNFa levels are always high in RA patients in the synovial
What do anti-TNFa do in RA
- they reduce production of cytokines as used to provide other cytokines
- reduces B-cells + T-cells in synovial fluid - as reduces chemokine that attract lymphocytes in synovial fluid
Give an example of anti-TNFa
structure
Infliximab this is part human and part mouse has FC region that communicates with immune system which is made from human genes. Not fully mouse as it would be rejeccted by body
etanercept - not antibody but has FC domain
How does abatacept work
- competes with CD28 on T-cells to bind on APC
- abatacept has CTLA-4 domain that allows it to bind on APC
- preventing CD28 binding prevents co-stimulation of T-cells so they are not fully activated.
How does tocilizumab
- blocks IL-6 receptor so that it will not be activated ]
- its a JAK inhibitor as IL-6 receptor (GP130 signals via JAK)
Besides RA what other conditions biologics used for
Crohn’s
Negatives of biologics
- Toxicity
- expensive
- Infliximab and entarcept contradicted into cardiac failure patients
- improvements short term need to be used long term
- need to be injected
- patient may start producing antibodies against the biologics
What do you use if TNF inhibitors and DMARDs fail
Rituximab + MTX
How does Rituximan work
binds to B-cells with CD20 and kills them this reduces release of IL-6 which is relesaed by B-cells, which causes inflammation
When are biologics recommneded and what treat is recommneded
only given if combination DMARDs fail
DAS28 greater than 5.1
should be given as biologics + MTX (NICE recommendation)
What are biosimilars
these are cheaper versions / generic versions with same genetic sequence but made by different company
