Lecture 30 - TNF treatment of RA Flashcards

1
Q

TNF is synthesis by ____ ______ and _ ____

A

activated macrophaes and T cells

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2
Q

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

A

transmembrane

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3
Q

TNF binds to one of two receptors:

A

TNFR1

TNFR2

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4
Q

TNF has a role in producing other..

A

proinflammatory cytokines

IL6
GM_CSF

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5
Q

TNF inhibition downregulated production of which effective cytokine inhibitors?

A

IL-10
IL-1 receptor antagonist
soluble TNF receptor

does this outbalance the good that it does?

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6
Q

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

A

therapeutically beneficial

- supported hypothesis that TNF drives inflammation

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7
Q

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

A

bowel disease

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8
Q

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

A

mouse variable region

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9
Q

Etanercept is a ___ _____

A

fusion protein

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10
Q

Adaimumab is a fully human …

A

mnoclonal antibody

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11
Q

Certolizumab pegol is a ____ monoclonal antibody

A

humanised

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12
Q

Golimumab is again a ______ antibody

A

humanised

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13
Q

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

A

60

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14
Q

What is an odds ratio?

A

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

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15
Q

OR=1 means

A

Variable (TNFi) has no effect

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16
Q

OR>1 means

A

higher odds of variable having an effect on outcome

17
Q

Primary failure is when

A

patient is exposed to treatment but has no improvement

18
Q

secondary failure can be caused by?

A

neutralising antibodies are created against the anti-TNF antibodies

19
Q

which treatment are patients most likely to remain on?

A

Etanercept

20
Q

what are the safely issues with TNF inhibitors?

A

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

21
Q

Abatacept vs. Adalimumab showed that

A

ABA non-inferior to ADA - not much difference

22
Q

Tocilizumab vs. Adalimmab showed…

A

TOC superior to ADA but associated with more adverse effects

23
Q

Tofacitinib is an oral drug that target ___cellular signal transduction,

A

intracellular

24
Q

What is the efficacy of Tofacitinib?

A

superior to placebo

comparable efficacy to adalimumab (the current market leader)

Treatment alternative for TNF inhibitor

25
what are the safely concerns of Tofacitinib (small molecule inhibitor)?
headaches infection elevated LDL opportunistic infection *can't use with other treatments