T1 L16: Biological therapies

Question 1

What are the adverse effects of synthetic DMARD’s?

Answer 1

Nausea
Loss of appetite
Diarrhoea
Rash, allergic reactions 
Headaches
Hair loss
Risk of infections (pneumonia)
Nephrotoxicity 
Hepatotoxicity

Question 2

How does the drug Tofacitinib work?

Answer 2

It’s a DMARD that selectively inhibits JAK1 and JAK3

It’s used for psoriatic arthritis and ulcerative colitis

Question 3

How does the drug Baricitinib work?

Answer 3

It’s a DMARD that reversibly inhibits JAK1 and JAK2

Question 4

How are biological therapies administered?

Answer 4

Parenterally because they’re proteins and would be digested

Question 5

When are biological therapies for rheumatoid arthritis reccommended?

Answer 5

• If the patient has failed to respond to at least 2 standard DMARD’s, one of which has to be methotrexate
• Patients disease score measured using DAS28 is over 5.1 on 2 occasions

Question 6

What are some biologics licenced in the UK?

Answer 6

• TNF-blockers: infliximab, etanercept, adalimumab, golimumab, certolizumab pegol
• Monoclonal antibodies against B-cells: rituximab
• T-cell co-stimulation inhibitor: abatacept
• Monoclonal antibodies against IL-6R: tocilizumab, sarilumab

IL-1R antagonist: anakinra

Question 7

What is the drug Infliximab?

Answer 7

A TNF-blocker used in combination with methotrexate

A partially humanised mouse monoclonal anti-hTNF-alpha antibody that neutralises free, membrane or receptor bound TNF-alpha

Question 8

What is the drug Etanercept?

Answer 8

A soluble TNF receptor dimer which binds to free and membrane bound TNF-alpha

Question 9

What is the drug Adalimumab?

Answer 9

Human IgG1 monoclonal anti-TNF-alpha antibody

Question 10

What is the drug Golimumab?

Answer 10

A human IgG1 monoclonal anti-TNF-alpha antibody

Question 11

What is the drug Certolizumab pegol?

Answer 11

A PEGylated anti-TNF-alpha antibody

Question 12

What are patients screened for before they’re given anti-TNF therapy?

Answer 12

Anything that could be made worse with immunosuppression

Eg. TB, multiple sclerosis, recurrent infections, leg ulcers, past history of cancer

Question 13

How does the drug Rituximab work?

Answer 13

It opsonises B-cells so they get killed in 3 ways:

Complement mediated cytotoxicity
Antibody-dependent cell mediated cytotoxicity,
Apoptosis

Question 14

How does the drug Abatacept work?

Answer 14

It’s a competitive inhibitor of CD28 cells which causes an increased threshold for activation

Question 15

What is the drug Tocilizumab?

Answer 15

A humanised anti-IL6 receptor monoclonal antibodie

Question 16

What is the drug Sarilumab?

Answer 16

A fully human monoclonal antibody against IL-6R-alpha

Question 17

What is the drug Anakira?

Answer 17

An IL-1R antagonist

Question 18

What are some adverse effects of biological therapies?

Answer 18

• Increased risk of infection (nasopharyngitis, pneumonia, UTI’s) so people must avoid live vaccines and they should take the flu and pneumococcal vaccines before starting biological therapy
• Nausea
• Headache
• Hypertension
• Allergic reaction