Lecture 28 - RA Treatment

Question 1

Phase I clinical trials
1)
2)

Answer 1

1) Test intervention for the first time in humans

2) Small group (20-80) to evaluate safety

Question 2

Phase II clinical trials
1)
2)
3)

Answer 2

1) Determine efficacy
2) Further test safety
3) Larger group of people (several hundred)

Question 3

Phase III clinical trials
1)
2)

Answer 3

1) Compare drug to current gold standard therapy

2) Large group (several hundred to thousands)

Question 4

Phase IV clinical trials
1)
2)

Answer 4

1) Post-marketing surveillance

2) Monitor efficacy and adverse events over a long period of time

Question 5

SPIRIT 2013

Answer 5

Standard Protocol Items: Recommendations of Interventional Trials

For optimal clinical trial design

Question 6

Tenants of Standard Protocol Items: Recommendations of Interventional Trials
1)
2)
3)
4)
5)

Answer 6

1) Ethical
2) Double-blind
3) Randomisation
4) PLacebo/control
5) Adequate size/power

Question 7

Therapeutic window of opportunity

Answer 7

First three months after symptoms onset

Question 8

Why try to treat in the first three months after symptoms onset?
1)
2)
3)

Answer 8

1) Hamper disease progression
2) Hamper disease burden
3) Reduce need for biologic disease-modifying antirheumatic drugs

Question 9

bDMARD

Answer 9

Biologic disease-modifying antirheumatic drug

Question 10

Important insight in RA therapy

Answer 10

Approach is more important than agent

Question 11

Approach is more important than agent

Answer 11

Intensive, multidrug therapy has a greater effect on outcomes than does the use of a specific drug

Question 12

Treat-to-target
1)
2)
a)
b)

Answer 12

1) Aim for remission or low disease activity
2) By DAS28 criteria
a) Low disease [2.6,3.2]
b) Remission (below 2)

Question 13

Therapeutic approach in RA
1)
2)
3)

Answer 13

1) Treat early
2) Treat to target
3) Intensive therapy

Question 14

TICORA

Answer 14

Tight intensive control of RA

Question 15

Do adverse events increase with more intense RA treatments?

Answer 15

No

Question 16

Pharmacological agents use to treat RA
1)
2)
3)
4)
5)

Answer 16

1) Analgesics
2) NSAIDS
3) Glucocorticoids
4) Synthetic disease-modifying antirheumatic drugs (DMARDs)
5) Biologic disease-modifying antirheumatic drugs (bDMARDs)

Question 17

Way around the ethical issue of giving some RA patients a placebo in clinical trials

Answer 17

Compare current treatment with new drug

Question 18

Disease-modifying antirheumatic drugs
1)
2)
3)
4)
5)
6)
7)
8)

Answer 18

1) Methotrexate
2) Sulphasalazine
3) Antimalarial drugs
4) Leflunomide
5) Gold salts
6) Auranofin (oral gold salt)
7) Ciclosporin A
8) Azathioprine

Question 19

Initial DMARD of choice for most patients

Answer 19

Methotrexate

Question 20

Anchor drug

Answer 20

Central component of many multi-drug therapies

EG: Methotrexate

Question 21

Methotrexate mode of action

Answer 21

Not fully known

Maybe a metabolite inhibitor?

Question 22

Common RA triple therapy

Answer 22

Methotrexate, sulfasalazine, hydroxychloroquine

Question 23

Results of a study comparing different DMARD therapies
1)
2)
3)

Answer 23

1) Most effective was methotrexate, sulfasalazine, hydroxychloroquine combination
2) Second-most effective was sulfasalazine and hydroxychloroquine combination
3) Least effective was methotrexate

Question 24

When are bDMARDs used?

Answer 24

When a patient fails to respond to DMARDs

Question 25

``` Classes of bDMARDs 1) 2) 3) 4) 5) ```

Answer 25

1) TNF inhibitors 2) IL-1 antagonists 3) IL-6 receptor antagonists 4) Cytotoxic T lymphocyte antigen 4 (CTLA4) ligand (co-stimulation modifier) 5) B-cell depleting agents (anti-CD20)

Question 26

Proportion of licensed bDMARDs that are TNF inhibitors

Answer 26

Currently 9 licensed bDMARDs, 5 of which are anti-TNF

Question 27

``` Anti-TNF bDMARDs 1) 2) 3) 4) 5) ```

Answer 27

1) Adalimumab 2) Certolizumab pegol 3) Etanercept 4) Golimumab 5) Infliximab

Question 28

Adalimumab

Answer 28

TNF blockade

Question 29

Abatacept

Answer 29

T cell costimulation blocker (CTLA4 ligand)

Question 30

Anakinra

Answer 30

Recombinant IL-1 receptor antagonist

Question 31

Tocilizumab

Answer 31

IL-6 receptor blockade

Question 32

How does Anakinra work?

Answer 32

It acts as a competitive inhibitor of IL-1 (it binds IL-1R)

Question 33

Drug that binds IL-1R

Answer 33

Anakinra

Question 34

Drug that binds to IL-6R

Answer 34

Tocilizumab

Question 35

Drug that binds to CD80/CD86

Answer 35

Abatacept

Question 36

When do B cells express CD20?

Answer 36

Between pro-B and memory B stages. | Not expressed on plasma cells

Question 37

PBS criteria for bDMARD therapy in Australia 1) 2) 3)

Answer 37

1) Failed six months of intensive DMARD (two agents, for minimum of three months each) 2) Erythrocyte sedimentation rate over 25mm/hour or C-reactive protein over 15mg/L 3) Over 20 active swollen joints or over 4 major large joints swollen

Question 38

Major joints

Answer 38

Elbow, wrist, knee, shoulder, hip