RA monoclonals/biologic DMARDs

Question 1

Etanercept

Answer 1

TNF alpha decoy receptor

Soluble p75 receptor fused to Fc portion of human IgG

Question 2

Infliximab

Answer 2

TNF alpha blocker

Binds soluble TNF AND TNF that has already docked hence opsonising that cell.

Chimeric monoclonal
The only IV TNF agent.

Question 3

Adalimumab

Answer 3

TNF alpha blocker

Human monoclonal
Useful in those who fail TNF blockers and are methotrexate resistant.

Question 4

Golimumab

Answer 4

TNF alpha blocker

Human monoclonal

Question 5

Certolizumab

Answer 5

TNF alpha blocker

Humanised Fab fragment

Question 6

Tocilizumab

Answer 6

RA drug

Binds and inhibits soluble and membrane bound IL-6 receptors

Don’t have to give with methotrexate so good if cannot tolerate. Mtx.
CYP 3A4 interactions.
NEUTROPAENIA, dyslipidaemia

Question 7

Abatacept

Answer 7

Blocks costimulation of T cells by binding CD 80/86 AKA B7 on antigen presenting cells.

LOOKS LIKE -fusion protein composed of the extracellular domain of CTLA-4 with the hinge, CH2, and CH3 domains of IgG1

Question 8

Rituximab

Answer 8

Anti CD-20- chimeric human/mouse

Widely expressed on B cells, from early pre-B cells to later in differentiation, but it is absent on terminally differentiated plasma cells.
Not stem cell, pro B cell or plasma cell but everything else.

BETTER RESPONSE IF seropositive disease.

Question 9

How can you assess B cell depletion in someone on Rituximab?

Answer 9

Check CD19 levels

Question 10

Rituximab side effects

Answer 10

Serious infusion reaction with first time- premedicate with antihistamine and steroids
Serious infections but no inreased risk of TB
PML

Question 11

Tofacitinib

Answer 11

RA drug

New oral JAK inhibitor (JAK 3, JAK 1)
Also good in methotrexate resistant RA

Normal pathway is to do with binding of CK to receptor activating JAK mediated pathways–>STAT family activation–>lymphocyte differentiation and immune regulation

Raised transaminases, neutropaenia, increased HDL and LDL cholesterol, transaminitis

Question 12

Denosumab

Answer 12

Humanised monoclonal Ab against RANKL–>reduces osteoclastogenesis

Inhibits errosive damage in RA but no difference with disease activity

Question 13

Precautions with TNF blockade?

Answer 13

TB
CCF- avoid if NYHA 3 or above
Demyelinating disease
Lymphoma
Lupus like syndrome or serology
Cancer last five years- don't give (called tumour necrosis factor for a reason!). No increase solid tumour risk but increase skin cancer risk

Question 14

Belimumab

Answer 14

Lupus drug

Human monoclonal against anti-BAFF ( a B cell CK)
This means you get inhibition of B cell survival and activation.

Definite modest effect in people who have pos dsDNA, low complement and high disease activity.
Not ever used so far in renal/CNS disease

Question 15

Secukinumab

Answer 15

Ank spond drug and psoriatic arthritis drug

anti IL-17A

Idea is to target IL-23/Th17 axis
Effective if TNF naive or nonresponsive, good in enthysitis/dactylitis
NO TB or MS risk 
Mucosal candida
No effect on IBD or uveitis

Question 16

Ustekinumab

Answer 16

Psoriatic arthritis drug

Monoclonal Ab to shared p40 subunit of IL-12 and IL-23
Good in spinal disease, dactylitis, enthesitis
Low infection risk
Less effective than TNF for peripheral arthritis

Question 17

Apremilast

Answer 17

Psoriatic arthritis

Oral small inhibitro of PDE4 enzyme–>alters expression of inflammatory mediators at the level of mRNA expression
No infection or malignancy risk
Only 75% as good as TNF inhib

Question 18

TNF blockers incrase risk of what kind of cancer?

Answer 18

non melanoma skin