Anti-TNF and B cell targeting in rheumatoid arthritis Flashcards
What is Rheumatoid arthritis?
An inflammatory joint disease characterised by an activated immune system and chronic inflammation.
What are the symptoms of RA?
Pain, stiffness, limited function, and joint destruction. There will also be extra-articular manifestations.
What is the pathogenesis of RA?
In a rheumatoid joint there is inflammation of numerous cell types, angiogenesis, and an inflamed synovial membrane.
What radiological changes are there in RA?
Erosion of the joints.
What is the etiology of RA?
The etiology of RA is multifactorial. There is a genetic predisposition and environmental factors like smoking, overweight, and hormonal factors (female).
Why are biomarkers needed for RA?
For a more accurate disease model, understanding how genetic heterogeneity explains phenotypic heterogeneity, and pathway identification (therapeutic targeting).
Which genes are possibly associated with RA onset?
HLA-DR ((self)antigen-presentation), PTPN22 (lymphocyte activation), CD40 (APC-Tcell interaction).
Which antibodies are used in diagnostics of RA?
IgM Rheumatoid factor (IgM-RF)
Anti-citrullinated protein antibodies (ACPA)
ACPA is more specific for RA, IgM-RF is more sensitive.
What is Rituximab?
An anti-CD20 that has multiple mechanisms of action that cause B-cell depletion. It has a long term effect. It doesn’t target the cells that mainly produce the auto-antibodies: the plasma cells. This is because they don’t express CD20. However, eventually, there is a reduction in plasma cells because old, dead plasma cells are not replaced by new ones because the B-cells have been depleted. This means that there is still not always a reduction of auto-antibodies.
It has better effects in ACPA+ RA, because that fits with Rituximab’s mechanism of action.
What is Abatacept?
Abatacept is a CTLA4-Ig that results in T-cell modulation and less T-cell activation. It is possibly more effective in ACPA+ RA. Side-effects are typically mild, not a lot of problems with infections etc.
What are JAK inhibitors?
They are from the last 5 years. They are oral, small molecules –> easy!
• Tofacitinib (JAK1/3 specific)
• Baricitinib (JAK1/2 specific)
• More types in development!
They are safe and effective in RA
• Downsides:
o more Varicella-zoster virus infection: shingles/”gordelroos”
o High doses: increased risk of thrombosis, maybe because of a JAK isoform.
What is a downside of biologics?
Increased risk of infection and more severe course, especially in elderly patients.
