Lecture 30 - TNF treatment of RA

Question 1

TNF is synthesis by ____ ______ and _ ____

Answer 1

activated macrophaes and T cells

Question 2

TNf is a _______ protein that is cleaved to form soluble TNF-a

Answer 2

transmembrane

Question 3

TNF binds to one of two receptors:

Answer 3

TNFR1

TNFR2

Question 4

TNF has a role in producing other..

Answer 4

proinflammatory cytokines

IL6
GM_CSF

Question 5

TNF inhibition downregulated production of which effective cytokine inhibitors?

Answer 5

IL-10
IL-1 receptor antagonist
soluble TNF receptor

does this outbalance the good that it does?

Question 6

Administered in hampster monoclonal anti-mouse TNF antibody what was the outcome?

Answer 6

therapeutically beneficial

- supported hypothesis that TNF drives inflammation

Question 7

Anti-TNF has expanded as a treatment to what, which is also evident in TNF transgenic mice?

Answer 7

bowel disease

Question 8

infliximab is a chimeric (mouse//human) with a ___ variable region

Answer 8

mouse variable region

Question 9

Etanercept is a ___ _____

Answer 9

fusion protein

Question 10

Adaimumab is a fully human …

Answer 10

mnoclonal antibody

Question 11

Certolizumab pegol is a ____ monoclonal antibody

Answer 11

humanised

Question 12

Golimumab is again a ______ antibody

Answer 12

humanised

Question 13

___% of treated patients in most trials will achieve a ACR20 (improvmenet criteria) - only 20% getting a ACR70

Answer 13

60

Question 14

What is an odds ratio?

Answer 14

Odds that an outcome will occur ina group exposed to a variable of intetest, compared to the odds of the outcome occuring in a group not exposed to the same variable of interest

OR=1 variable (TNFi) has no effect

OR>1 higher odds of variable having an impact

Question 15

OR=1 means

Answer 15

Variable (TNFi) has no effect

Question 16

OR>1 means

Answer 16

higher odds of variable having an effect on outcome

Question 17

Primary failure is when

Answer 17

patient is exposed to treatment but has no improvement

Question 18

secondary failure can be caused by?

Answer 18

neutralising antibodies are created against the anti-TNF antibodies

Question 19

which treatment are patients most likely to remain on?

Answer 19

Etanercept

Question 20

what are the safely issues with TNF inhibitors?

Answer 20

injection site reactions
infusion reactions

Neutropenia - oversuppression of immune system

Infection - upper resp. tract & soft tissue

heart failure

Demyelinating disease

malignancy - although increased risk anyway with RA

induction of autoimmune diseases

Question 21

Abatacept vs. Adalimumab showed that

Answer 21

ABA non-inferior to ADA - not much difference

Question 22

Tocilizumab vs. Adalimmab showed…

Answer 22

TOC superior to ADA but associated with more adverse effects

Question 23

Tofacitinib is an oral drug that target ___cellular signal transduction,

Answer 23

intracellular

Question 24

What is the efficacy of Tofacitinib?

Answer 24

superior to placebo

comparable efficacy to adalimumab (the current market leader)

Treatment alternative for TNF inhibitor

Question 25

what are the safely concerns of Tofacitinib (small molecule inhibitor)?

Answer 25

headaches
infection
elevated LDL
opportunistic infection

*can’t use with other treatments