MSI pharm- biological therapies

Question 1

Methotrexate drug class?

Answer 1

anti-metabolite

Question 2

Drug class of Adalimumab, Tocilizumab, Rituximab ?

Answer 2

Monoclonal antibodies

Question 3

When someone is diagnosed with RA, what are the three classes of drugs they are typically started on after their first visit?

Answer 3

NSAIDs and Glucocorticoids (for symptom relief) and also a DMARD (such as methotrexate) to slow the clinical and radiographic progression of RA

(Remember that DMARDs can take 8-12 weeks to start working, so they need sx relief initially!)

Question 4

What is the first choice DMARD, aka “the gold standard”?

Answer 4

Methotrexate

Question 5

** MOA for Methotrexate?

Answer 5

Antimetabolite (folate analogue), inhibits cell proliferation
Increases adenosine level (anti-inflammatory- Reduces inflammation quickly and keeps it under tight control)
Reduces the production of damaging polyamines
Induces apoptosis of activated CD4+ and CD8+ T-cells

Question 6

What is considered the “Anchor drug” in combination therapies for AI disease?

Answer 6

Methotrexate

Question 7

What type of supplementation is required along with Methotrexate administration?

Answer 7

Folic acid- Orally or subcut 1/week

Question 8

** Side effects of DMARDs/Methotrexate (30% of patients experience adverse effects)

Nausea
Loss of appetite
Diarrhoea
Rash, allergic reactions
Headache
Hair loss
Risk of infections (pneumonia)
Hepatotoxicity (metabolism) 
Bone marrow suppression & thrombocytopenia 
\_\_\_\_\_\_\_\_\_ toxicity (route of elimination)

Answer 8

Kidney

Question 9

Biological therapy is a form of treatment that uses portions of the body’s natural immune system to treat a disease.

Biological DMARDs (bDMARDs) are proteins derived from human genes genetically engineered to inhibit precise components of the immune system- such as targeting a single __________
TNF-blockers (TNF- Tumour Necrosis factor)
Drugs targeting IL-1, IL-6 , B-cells and T-cells

Answer 9

cytokine

Question 10

Biological therapy nomenclature:

“-cept” refers to fusion of a receptor to the __ part of human immunoglobulin G1 (IgG1)

Answer 10

Fc

Question 11

Biological therapy nomenclature:

“-mab” indicates a _________ antibody (mAb)

Answer 11

monoclonal

Question 12

Biological therapy nomenclature:

“-ximab” indicates a ________ mAb

Answer 12

chimeric- partially human, partially animal derived, like mouse derived

Question 13

Biological therapy nomenclature:

“-zumab” indicates a ________ mAb

Answer 13

humanized

Question 14

Biological therapy nomenclature:

“-umab” indicates a fully ______ mAb

Answer 14

human

Question 15

** What is one of the key cytokines in the process of driving inflammation?

Answer 15

TNF- Can be derived from macrophages, T cells

Question 16

** Enzymes that are very destructive (produced by synovial fibroblasts). Responsible for the cartilage destruction of RA (along with PGE2 and IL-6)

Answer 16

Matrix metalloproteases

Question 17

Biological therapies are protein drugs that are administered …

Answer 17

parenterally (or subcut)

Question 18

Biologics are extremely expensive, so NICE has strict guidelines for eligibility:

Patient has failed to respond to treatment with at least two standard (synthetic) DMARDs, one of which must be ___ (unless patient cannot take it for medical reason)

Patient’s RA disease activity score (DAS 28) is measured at 3.2 (moderate RA activity) or over, on two occasions, one month apart

Answer 18

MTX

Question 19

MOA for Adalimumab?

Answer 19

TNF-blocker

Question 20

MOA for Rituximab?

Answer 20

Monoclonal antibody against B cells

Question 21

MOA for Tocilizumab?

Answer 21

Monoclonal antibodies against IL-6R

Question 22

Method of administration for Adalimumab (fully human anti-TNF monoclonal Ab)

Answer 22

subcut injection

Question 23

What is the biggest and most common ADE of Adalimumab?

Answer 23

Risk of infection

Question 24

Considerations for prescribing anti-TNF therapy (Adalimumab):

Patients screened before starting treatment to exclude an increased risk of side effects, in particular for a past history of ____________, multiple sclerosis, recurrent infection, heart failure (III/IV).

Chest X-ray to be taken to exclude signs of previous TB and to exclude signs of heart failure

Screen for HIV, Hepatitis B and C

Live vaccines, against e.g. yellow fever or polio, should be avoided.

Answer 24

tuberculosis (TB)

Question 25

Adalimumab should not be prescribed with

Answer 25

other biologic therapies, as it increases the risk of infection

Question 26

Which biologic drug is a partially humanized anti-CD20 monoclonal antibody?

Answer 26

Rituxumab

Question 27

_________ opsonized B-cells are attacked and killed by three mechanisms:

Complement mediated cytotoxicity

2-3)Antibody-dependent cell mediated cytotoxicity (ADCC) – FcgR or CR (complement receptor) mediated opsonic phagocytosis

4) Apoptosis

Answer 27

Rituximab

Question 28

Biologic drug that is a humanized anti-IL-6 receptor monoclonal antibody used to treat juvenile idiopathic arthritis, Giant cell arteritis, critical Covid-19

Answer 28

Tocilizumab

Question 29

Risk of TB (or reactivating latent TB infection) is most associated with which biologic drug?

Answer 29

Adalimumab (anti-TNF)

Question 30

Which two biologic therapies are Contraindicated in pregnancy and while breast feeding?

Answer 30

Rituximab, Tocilizumab

Question 31

Adverse effects of biological therapies:
** Increased risk of __________: Upper respiratory tract infections (nasopharyngitis), pneumonia, urinary tract infections and tuberculosis.

It is recommended to receive influenza and pneumococcal vaccines before embarking on biological therapy

Avoid live vaccines

Booster Covid

Answer 31

infections

Question 32

Which biologic drug is associated with increased Lipid Levels?

Answer 32

Tocilizumab

Question 33

Combination therapy- this is the concept of taking two immunosuppressants together – with regards to biologics. This is usually __________.
** This increases the response of biologics.
Reduces immuno-genicity of the biologics

Answer 33

methotrexate