11 - Treatment Options for Rheumatoid Arthritis

Question 1

How do you diagnose RA

Answer 1

Clinical diagnosis

ACR/EULAR criteria

Question 2

What are the 4 ACR/EULAR criteria

Answer 2

Joint involvement
Serology 
Acute phase reactants
Duration of symptoms
need >6/10 for diagnosis

Question 3

How do you manage RA

Answer 3

1) Pain relief
2) Modification of disease progression (ASAP)
3) Adjunct therapy

Question 4

What is the pain relief given in RA

Answer 4

Same as OA
Analgesics
NSAIDs
COX-2 inhibitors

Question 5

When should DMAR be given

Answer 5

within 3months of symptoms

Question 6

Gold standard DMAR

Answer 6

Methotrexate

Question 7

What combination of DMARDs would you give to a newly diagnosed RA patient

Answer 7

Methotrexate
at least one other DMARD
Short term glucocorticoids

Question 8

What would you give to a newly diagnosed RA patient who is pregnant

Answer 8

DMARD monotherapy

Question 9

What would you do with this patient

Recent-onset RA and receiving combination DMARD and satisfactory control

Answer 9

Cautiously reduce dosage to a level that still controls the disease

Question 10

How long before the benefit of methotrexate is seen?

Answer 10

3-12 weeks

Question 11

How often do you give methotrexate

Answer 11

Orally
once a week
in the same day (start with a higher dose and then decrease it when controlled)

Question 12

MoA of methotrexate

Answer 12

Folic Acid antagonist
Limits DNA and RNA synthesis
Inhibits dihydrofolate reductase and thymidylate synthetase
Blocks the production of pro inflammatory cytokines

Question 13

Side effects of methotrexate

Answer 13

Can cause liver problems

Can affect blood count

Question 14

What is sulfasalazine

Answer 14

Combination of sulfapyridine and salicylate with an azo bond

Question 15

How is sulfasalazine absorbed

Answer 15

Not well absorbed across the gut (<15%)

so metabolised by gut bacteria into 5-ASA which is better absorbed

Question 16

What is the MoA of sulfasalazine

Answer 16

Not well understood

some think treats local gut inflammation which causes a knock on effect to help with joint inflammation

Question 17

What else can sulfasalazine treat?

Answer 17

Ulcerative collitis

Question 18

What is hydroxychloroquine

Answer 18

Anti-malarial drug

Question 19

What is the MoA of hydroxychloroquine

Answer 19

Blocks toll like receptor 9
Decreases activation of dendritic cells
do not get interaction between dendritic and b cells

Question 20

What is the side effect of hydroxychloroquine

Answer 20

Rash

Question 21

What is leflunomide

Answer 21

Efficacy similar to methotrexate

Inhibits pyrimidine biosynthesis through inhibiting dihydroorate dehydrogenase to inhibit DNA and RNA synthesis

Question 22

Examples of TNFa blockers

Answer 22

Etanercept
Infliximab
Adalimumab

Question 23

Etanercept

Answer 23

Fusion protein human TNF receptor 2 and Fc human IgG1
Binds and stops TNFa from signalling
1-4 weeks for effect

Question 24

Infliximab

Answer 24

Monoclonal antibody against TNFa
Against the mouse binding site of TNFa with the remaining human 75% IgG1
Days to weeks for effect

Question 25

Adalimumab

Answer 25

Human TNFa monoclonal antibody | Binds TNFa both soluble

Question 26

Interleukin 1 blockers

Answer 26

Anakinra Canakinumab Rilonacept

Question 27

Anakinra

Answer 27

Human recombinant IL-1 receptor antagonist Binds to IL-1R preventing IL-1 binding Differs from IL-1 by addition of N-terminal methionine (binds to IL-1R with same affinity as IL-1) 2-4 weeks to have an effect

Question 28

Canakinumab

Answer 28

Human monoclonal antibody targets IL1-B trials for COPD and gout

Question 29

Rilonacept

Answer 29

Dimeric fusion protein extracellular domain of IL1R1 and Fc human IgG1 Used more for acute gout

Question 30

B cell monoclonal antibodies

Answer 30

Used if unresponsive to anti-TNFa | Rituximab

Question 31

Rituximab

Answer 31

Chimeric monoclonal antibody against CD20 on the surface of B-cells Destroys malignant and normal B-cells effects after 3 months of infusions

Question 32

Abatacept

Answer 32

Fusion protein IgG fused to extracellular domain of CTLA-4 | Prevents 2nd signal being delivered to T cell

Question 33

Betalacept

Answer 33

Anti-CD28, modulate T-cell signalling

Question 34

Tocilizumab

Answer 34

Human monoclonal antibody against IL-6 receptor | given in combo with methotrexate

Question 35

Neutralising Anti Drug Antibodies

Answer 35

directly interferes with the biological drugs ability to work

Question 36

Non-neutralising Anti Drug Antibodies

Answer 36

May form immune complexes around injection site reducing drug concentration and pharmacokinetics

Question 37

T CELL

Answer 37

Abatacept | Belatacept