IMMUNO: Immunosuppressive therapies Flashcards
What is the MOA of corticosteroids?
Glucocorticoids - inhibit phospholipase A2 –x–> arachidonic acid, eicosanoids by COX
Name 2 eicosanoids.
Prostaglandins, leukotrienes
What effect do steroids have on
1) phagocytes
2) lymphocytes
1) reduce trafficking + enzyme release but increases neutrophil count
2) lymphopenia, less Abs, more apoptosis
Which lymphocyte numbers fall most in corticosteroid use?
CD4>CD8>B cell
What bone complication is a severe one associated with corticosteroid use?
Avascular necrosis
List 3 cytotoxic/anti-proliferative drugs.
Cyclophosphamide
Mycophenolate
Azathioprine
MOA: inhibit DNA synthesis
What infection is associated with cyclophosphamide? What malignancy?
PCP
Bladder, haematological, skin (non-melanoma)
Why can you get blood in urine with cyclophosphamide?
Causes haemorrhagic cystitis
Which cytotoxic is infection less common with?
Azathioprine
Which polymorphism is dangerous with azathioprine use?
TPMT - these patients will be unable to metabolise azathioprine
(check FBC after starting)
What is a side effect of all cytotoxic therapies?
Bone marrow suppression
Which infection is associated with MMF?
PML (JC) and herpes reactivation
What hypersensitivity is treated with plasmapharesis?
Type II e.g. Goodpasture and MG or ABO/transplant rejection
What is the MOA of calcineurin inhibitors?
reduce IL-2 production and IL-2R expression –> inhibit T cell proliferation and function
What are 3 uses of CIs?
Transplants
SLE
Psoriatic arthritis
Give 2 examples of CIs.
Tacrolimus
Ciclosporin
(NOT Sirolimus - this is an mTOR inhibitor)
What is the MOA of mTORi? Give one example.
Inhibit T cell proliferation and function by blocking signalling. Sometimes called rapalogues because they act like mTORs natural inhibitor rapamycin (macrolide).
e.g. Rapamycin (Sirolimus)
What is the MOA of JAKi/Jakinibs? Give 1 example.
Inhibit: JAK-STAT signalling –> gene transcription –> inflammatory cytokines
e.g. TofaCITINIB
What are 3 uses of Jakinibs?
RhA
Psoriatic arthritis
Axial spondyloarthritis
What is the MOA of PDE4i? Give one example.
Inhibit: PDE4–> cAMP upregulation –> gene transcription via PKA –>cytokine production
e.g. ApreMILAST
What are 2 uses of PDE4 inhibitors?
Psoriasis
Psoriatic arthritis
How does abatacept differ from ipilimumab?
Abatacept = CTLA4-Ig --\> aims to suppress Ipilimumab = anti-CTLA4 mAb --\> aims to increase immune response
Name an anti-CD25 drug and its aim.
Basiliximab - immunosuppress, targets T cells by blocking IL-2 signalling
Name an ati-a4b7 integrin drug and its aim.
Vedolizumab - immunosuppress by stopping lymphocyte migration
Name a CTLA4-Ig and its aim.
Abatacept - immunosuppress, targets T cells
What cells do these therapies suppress?
- rabbit ATG, basiliximab, abatacept
T cells
What cells do these therapies suppress?
- rituximab
B cells
What cells do these therapies suppress?
-vedolizumab
Lymphocyte migration
What is a use of ATG? What is its MOA?
Allograft rejection - acts by T cell depletion and modulation
What is a use of basiliximab/anti-CD25?
PROPHYLAXIS of allograft rejection
What is the use of Abatacept? How frequently is it given?
RhA IV 4 weekly or SC weekly
What are the uses of rituximab? What is its MOA?
RhA
Lymphoma
SLE
MOA -depletes mature B cells
Which RhA therapy only requires 2 doses IV 6-12 monthly?
Rituximab
What infection is associated with rituximab use? Which conditions can get worse on rituximab?
PML (JC)
Cardiovascular conditions worsen
What is a use of vedolizumab?
IBD - IV every 8 weeks
Name 2 complications of vedolizumab use.
Hepatotoxicity
Infection - PML
What are anti-4/5/13 treatments used for?
Eczema and asthma
What are anti-IL-6R therapies used for?
RhA
Which cytokines may be targeted in FMF?
TNF-alpha and IL-1 suppression
What are anti-IL17/23 treatments used for?
Spondyloarthropathies and related conditions i.e. axial spondyloarthritis, psoriasis, psoriatic arthritis, IBD (not IL-17)
What are anti-TNF alpha treatments used for?
RhA and ankylosing spondylitis
Psoriasis and psoriatic arthritis
IBD
FMF
Name a anti-TNF alpha antibody.
Infliximab
Adalimumab
Certolizumab
Golimumab
What is a specific SE of anti-TNF alpha antibody therapy? What infections are associated?
Demyelination
TB, HBV/HCV
Name a TNF alpha antagonist. What are its uses?
Etanercept - RhA, spondylitis, psoriasis
What are the targets of Etanercept?
Inhibits TNF ALPHA AND BETA
What anti-cytokine for RhA may cause lupus-like conditions?
Etanercept
What drives IL-1?
Inflammasome
What treatment is used in Castleman’s disease? What is its MOA?
IL-6 blockade
MOA: reduces macrophages, T, B and neutrophil activation.
Which anti-cytokine therapy may cause elevated lipids?
IL-6 blockade
Which T cell responses is IL23 and IL17 involved with?
Th17
What are the subunits of IL-23 targeted by therapy?
p40 and p19
What is a SE of targeting IL-23?
Infection - TB
Which T cell response is important in asthma and eczema?
Th2
IL-13 blockade - eczema
IL-5 blockade - asthma
IL4R - both
What is OPG?
Soluble RANKL decoy which is made by osteoblasts to prevent osteoclast interaction
Which cells express RANKL?
RANKL = osteoBLASTS
Name a RANKL inhibitor.
Denosumab
Name 2 types of infusion reactions seen with biologics.
IgE mediated - urticaria etc
Non-classical type 1 - headache, fevers, myalgias
When do infusion site reactions peak?
48hrs at the previous site
When is risk of PML highest in immunosuppressant use?
Multiple biologics used at the same time - JC destroys oligodendrocytes
