Inflammatory Conditions/Biologics

Question 1

____ is a chronic inflammatory, systemic autoimmune disease

Answer 1

Rheumatoid Arthritis

Question 2

What are risk factors for RA?

Answer 2

• Age
• Females
  -Genetics (HLA epitope)
  -Exposures
  -Microbiomes

Question 3

What are some complications of RA?

Answer 3

Permanent joint damage/deformity, vasculitis, Feltys syndrome

Question 4

What symptoms differentiate RA and osteoarthritis?

Answer 4

RA joint pain is symmetric, in small joints, warm, red, and tender

Question 5

Other than joint pain what are some other symptoms of RA?

Answer 5

fatigue, fevers, weight loss, other organ involvement, firm moveable nodules near joints

Question 6

What age is the typical onset of RA?

Answer 6

35-60 y/o but can also affect children (JRA)

Question 7

What is feltys syndrome?

Answer 7

A late complication of RA where the spleen is enlarged, patients are neutropenic and have frequent infections, often treated by a spleenectomy

Question 8

Describe the pathology of RA

Answer 8

1. innate immune system activated in synovial compartment
2. expression of inflammatory cytokines
3. Activation of T helper cells Th1 & 17
4. More inflammatory cytokines
5. TNF-alpha dysregulation = excessive inflammation and destruction by macrophages
6. Autoantibodies such as RF also involved in response to

Question 9

What was traditionally first line treatment for RA?

Answer 9

NSAIDS and Corticosteroids

Question 10

What are other disease modifying anti rheumatic drugs (DMAR)? What do they all have in common?

Answer 10

• Methotrexate
• Hydroxychloroquine
• Sulfasalzine
• Gold Salts
• Azathioprine

All Suppress the immune system resulting in frequent and severe infections often requiring hospitalization, also cause malignancy

Question 11

Why do we need TNF-alpha?

Answer 11

TNF-alpha is a proinflammatory cytokine that is pyrogenic, activates macrophages, fights invaders, and cancer.

Question 12

_______ is a chronic inflammatory autoimmune disease affecting multiple organ systems

Answer 12

Systemic Lupus Erythematosus (SLE)

Question 13

Review Lupus diagnostic criteria

Answer 13

Question 14

Describe pathology of SLE

Answer 14

Question 15

What causes organ damage in lupus?

Answer 15

Deposition of IgG autoantibodies (ANAs) and immune cell complexes in microvasculature

Question 16

What are some complications of lupus?

Answer 16

glomerulonephritis, vasculitis, dermatitis, cutaneous lesions, encephalitis

Question 17

What are common symptoms of lupus?

Answer 17

fever, fatigue, weight loss, malar rash, MSK involvement, pulmonary symptoms, cardiovascular disease, renal disease, hematologic involvement

Question 18

What is first line treatment for lupus?

Answer 18

1. Hydroxychloroquine
2. NSAIDS, Glucocorticoids

Others:
Cyclophosphamide
Azathioprine
Methotrexate
Mycophenolate

Question 19

What are some biologics/targeted therapies for lupus?

Answer 19

Belimumab, Rituximab, Anifrolumab, Voclosporin

Question 20

Rituxumab MOA?

Answer 20

Depletes B cells

Question 21

Belimumab MOA?

Answer 21

inhibits B cells, first biologic for lupus

Question 22

Anifrolumab MOA
(SLE TX)

Answer 22

type 1 IFN inhibitor, reduces cytokines

Question 23

Voclosporin MOA?

Answer 23

calcineurin inhibitor T cell blocker (safer analog of cyclosporin)

Question 24

Up to 11% of _______ and _______ populations have plaque psoriasis

Answer 24

Caucasian and Scandinavian

Question 25

Is plaque psoriasis a genetic or autoimmune disorder?

Answer 25

associated with both genetic and autoimmune factors

Question 26

Describe plaque psoriasis pathology

Answer 26

Inflammation stimulates cytokines (TNF alpha) which recruit neutrophils, enhance angiogenesis, activate keratocytes, and prime T cells to attack releasing more cytokines in a viscous cycle

Question 27

What is first line treatment for plaque psoriasis?

Answer 27

Suppress immune system & decrease inflammation:

Topical - steroids, tar products, Vit D
Systemically - methotrexate, cyclosporin

Question 28

__________ is a TNF alpha blocking monoclonal antibody used to treat plaque psoriasis

Answer 28

Adalimumab (Humira)

Question 29

________ was the first TNF alpha blocking monoclonal antibody used to treat plaque psoriasis

Answer 29

Infliximab (Remicade) 1998

Question 30

How is adalimumab (Humira) administered and what are common side effects? (Plaque Psoriasis)

Answer 30

Bi-monthly injections

SA - injection site reactions, increased risk of infection

Less common - lymphoma, cytopenia, reactivation of TB

Question 31

How is Infliximab (remicade) administered and what are common side effects? (Psoriasis TX)

Answer 31

Infusions every 6-8 weeks

SA - respiratory infections, HA, cough, infusion reactions

Less common - lupus-like syndromes, infections, malignancies

Question 32

What are the two newer Psoriasis Treatments?

Answer 32

Ixekizumab (Taltz) and Ustekinumab (Stelara)

Question 33

How is Ixekizumab (Taltz) (Psoriasis TX) administered and what are common side effects?

Answer 33

Injection every 2-4 weeks

Less SA - low risk of infection (herpes, candida), better clinical results over years

Question 34

Ixekizumab (Taltz) MOA?

Answer 34

IL-17A high affinity, inhibitory monoclonal antibody

Question 35

Ustekinumab (Stelara) MOA?
(Psoriasis TX)

Answer 35

IL-12 and IL-23 inhibitory monoclonal antibody

Question 36

How is Ustekinumab (Stelara) administered and what are the SA?

Answer 36

Dosed by injection

Less SA - low risk of infection

Approved for use in other inflammatory conditions