IMMUNO: Immunosuppressive therapies

Question 1

What is the MOA of corticosteroids?

Answer 1

Glucocorticoids - inhibit phospholipase A2 –x–> arachidonic acid, eicosanoids by COX

Question 2

Name 2 eicosanoids.

Answer 2

Prostaglandins, leukotrienes

Question 3

What effect do steroids have on

1) phagocytes
2) lymphocytes

Answer 3

1) reduce trafficking + enzyme release but increases neutrophil count
2) lymphopenia, less Abs, more apoptosis

Question 4

Which lymphocyte numbers fall most in corticosteroid use?

Answer 4

CD4>CD8>B cell

Question 5

What bone complication is a severe one associated with corticosteroid use?

Answer 5

Avascular necrosis

Question 6

List 3 cytotoxic/anti-proliferative drugs.

Answer 6

Cyclophosphamide
Mycophenolate
Azathioprine

MOA: inhibit DNA synthesis

Question 7

What infection is associated with cyclophosphamide? What malignancy?

Answer 7

PCP
Bladder, haematological, skin (non-melanoma)

Question 8

Why can you get blood in urine with cyclophosphamide?

Answer 8

Causes haemorrhagic cystitis

Question 9

Which cytotoxic is infection less common with?

Answer 9

Azathioprine

Question 10

Which polymorphism is dangerous with azathioprine use?

Answer 10

TPMT - these patients will be unable to metabolise azathioprine

(check FBC after starting)

Question 11

What is a side effect of all cytotoxic therapies?

Answer 11

Bone marrow suppression

Question 12

Which infection is associated with MMF?

Answer 12

PML (JC) and herpes reactivation

Question 13

What hypersensitivity is treated with plasmapharesis?

Answer 13

Type II e.g. Goodpasture and MG or ABO/transplant rejection

Question 14

What is the MOA of calcineurin inhibitors?

Answer 14

reduce IL-2 production and IL-2R expression –> inhibit T cell proliferation and function

Question 15

What are 3 uses of CIs?

Answer 15

Transplants
SLE
Psoriatic arthritis

Question 16

Give 2 examples of CIs.

Answer 16

Tacrolimus
Ciclosporin

(NOT Sirolimus - this is an mTOR inhibitor)

Question 17

What is the MOA of mTORi? Give one example.

Answer 17

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)

Question 18

What is the MOA of JAKi/Jakinibs? Give 1 example.

Answer 18

Inhibit: JAK-STAT signalling –> gene transcription –> inflammatory cytokines

e.g. TofaCITINIB

Question 19

What are 3 uses of Jakinibs?

Answer 19

RhA
Psoriatic arthritis
Axial spondyloarthritis

Question 20

What is the MOA of PDE4i? Give one example.

Answer 20

Inhibit: PDE4–> cAMP upregulation –> gene transcription via PKA –>cytokine production

e.g. ApreMILAST

Question 21

What are 2 uses of PDE4 inhibitors?

Answer 21

Psoriasis
Psoriatic arthritis

Question 22

How does abatacept differ from ipilimumab?

Answer 22

Abatacept = CTLA4-Ig --\> aims to suppress 
Ipilimumab = anti-CTLA4 mAb --\> aims to increase immune response

Question 23

Name an anti-CD25 drug and its aim.

Answer 23

Basiliximab - immunosuppress, targets T cells by blocking IL-2 signalling

Question 24

Name an ati-a4b7 integrin drug and its aim.

Answer 24

Vedolizumab - immunosuppress by stopping lymphocyte migration

Question 25

Name a CTLA4-Ig and its aim.

Answer 25

Abatacept - immunosuppress, targets T cells

Question 26

What cells do these therapies suppress? - rabbit ATG, basiliximab, abatacept

Answer 26

T cells

Question 27

What cells do these therapies suppress? - rituximab

Answer 27

B cells

Question 28

What cells do these therapies suppress? -vedolizumab

Answer 28

Lymphocyte migration

Question 29

What is a use of ATG? What is its MOA?

Answer 29

Allograft rejection - acts by T cell depletion and modulation

Question 30

What is a use of basiliximab/anti-CD25?

Answer 30

PROPHYLAXIS of allograft rejection

Question 31

What is the use of Abatacept? How frequently is it given?

Answer 31

RhA IV 4 weekly or SC weekly

Question 32

What are the uses of rituximab? What is its MOA?

Answer 32

RhA Lymphoma SLE MOA -depletes mature B cells

Question 33

Which RhA therapy only requires 2 doses IV 6-12 monthly?

Answer 33

Rituximab

Question 34

What infection is associated with rituximab use? Which conditions can get worse on rituximab?

Answer 34

PML (JC) Cardiovascular conditions worsen

Question 35

What is a use of vedolizumab?

Answer 35

IBD - IV every 8 weeks

Question 36

Name 2 complications of vedolizumab use.

Answer 36

Hepatotoxicity Infection - PML

Question 37

What are anti-4/5/13 treatments used for?

Answer 37

Eczema and asthma

Question 38

What are anti-IL-6R therapies used for?

Answer 38

RhA

Question 39

Which cytokines may be targeted in FMF?

Answer 39

TNF-alpha and IL-1 suppression

Question 40

What are anti-IL17/23 treatments used for?

Answer 40

Spondyloarthropathies and related conditions i.e. axial spondyloarthritis, psoriasis, psoriatic arthritis, IBD (not IL-17)

Question 41

What are anti-TNF alpha treatments used for?

Answer 41

RhA and ankylosing spondylitis Psoriasis and psoriatic arthritis IBD FMF

Question 42

Name a anti-TNF alpha antibody.

Answer 42

Infliximab Adalimumab Certolizumab Golimumab

Question 43

What is a specific SE of anti-TNF alpha antibody therapy? What infections are associated?

Answer 43

Demyelination TB, HBV/HCV

Question 44

Name a TNF alpha antagonist. What are its uses?

Answer 44

Etanercept - RhA, spondylitis, psoriasis

Question 45

What are the targets of Etanercept?

Answer 45

Inhibits TNF ALPHA AND BETA

Question 46

What anti-cytokine for RhA may cause lupus-like conditions?

Answer 46

Etanercept

Question 47

What drives IL-1?

Answer 47

Inflammasome

Question 48

What treatment is used in Castleman's disease? What is its MOA?

Answer 48

IL-6 blockade MOA: reduces macrophages, T, B and neutrophil activation.

Question 49

Which anti-cytokine therapy may cause elevated lipids?

Answer 49

IL-6 blockade

Question 50

Which T cell responses is IL23 and IL17 involved with?

Answer 50

Th17

Question 51

What are the subunits of IL-23 targeted by therapy?

Answer 51

p40 and p19

Question 52

What is a SE of targeting IL-23?

Answer 52

Infection - TB

Question 53

Which T cell response is important in asthma and eczema?

Answer 53

Th2 IL-13 blockade - eczema IL-5 blockade - asthma IL4R - both

Question 54

What is OPG?

Answer 54

Soluble RANKL decoy which is made by osteoblasts to prevent osteoclast interaction

Question 55

Which cells express RANKL?

Answer 55

RANKL = osteoBLASTS

Question 56

Name a RANKL inhibitor.

Answer 56

Denosumab

Question 57

Name 2 types of infusion reactions seen with biologics.

Answer 57

IgE mediated - urticaria etc Non-classical type 1 - headache, fevers, myalgias

Question 58

When do infusion site reactions peak?

Answer 58

48hrs at the previous site

Question 59

When is risk of PML highest in immunosuppressant use?

Answer 59

Multiple biologics used at the same time - JC destroys oligodendrocytes