Inflammatory Conditions/Biologics Flashcards
____ is a chronic inflammatory, systemic autoimmune disease
Rheumatoid Arthritis
What are risk factors for RA?
- Age
- Females
-Genetics (HLA epitope)
-Exposures
-Microbiomes
What are some complications of RA?
Permanent joint damage/deformity, vasculitis, Feltys syndrome
What symptoms differentiate RA and osteoarthritis?
RA joint pain is symmetric, in small joints, warm, red, and tender
Other than joint pain what are some other symptoms of RA?
fatigue, fevers, weight loss, other organ involvement, firm moveable nodules near joints
What age is the typical onset of RA?
35-60 y/o but can also affect children (JRA)
What is feltys syndrome?
A late complication of RA where the spleen is enlarged, patients are neutropenic and have frequent infections, often treated by a spleenectomy
Describe the pathology of RA
- innate immune system activated in synovial compartment
- expression of inflammatory cytokines
- Activation of T helper cells Th1 & 17
- More inflammatory cytokines
- TNF-alpha dysregulation = excessive inflammation and destruction by macrophages
- Autoantibodies such as RF also involved in response to
What was traditionally first line treatment for RA?
NSAIDS and Corticosteroids
What are other disease modifying anti rheumatic drugs (DMAR)? What do they all have in common?
- Methotrexate
- Hydroxychloroquine
- Sulfasalzine
- Gold Salts
- Azathioprine
All Suppress the immune system resulting in frequent and severe infections often requiring hospitalization, also cause malignancy
Why do we need TNF-alpha?
TNF-alpha is a proinflammatory cytokine that is pyrogenic, activates macrophages, fights invaders, and cancer.
_______ is a chronic inflammatory autoimmune disease affecting multiple organ systems
Systemic Lupus Erythematosus (SLE)
Review Lupus diagnostic criteria
Describe pathology of SLE
What causes organ damage in lupus?
Deposition of IgG autoantibodies (ANAs) and immune cell complexes in microvasculature
What are some complications of lupus?
glomerulonephritis, vasculitis, dermatitis, cutaneous lesions, encephalitis
What are common symptoms of lupus?
fever, fatigue, weight loss, malar rash, MSK involvement, pulmonary symptoms, cardiovascular disease, renal disease, hematologic involvement
What is first line treatment for lupus?
- Hydroxychloroquine
- NSAIDS, Glucocorticoids
Others:
Cyclophosphamide
Azathioprine
Methotrexate
Mycophenolate
What are some biologics/targeted therapies for lupus?
Belimumab, Rituximab, Anifrolumab, Voclosporin
Rituxumab MOA?
Depletes B cells
Belimumab MOA?
inhibits B cells, first biologic for lupus
Anifrolumab MOA
(SLE TX)
type 1 IFN inhibitor, reduces cytokines
Voclosporin MOA?
calcineurin inhibitor T cell blocker (safer analog of cyclosporin)
Up to 11% of _______ and _______ populations have plaque psoriasis
Caucasian and Scandinavian
Is plaque psoriasis a genetic or autoimmune disorder?
associated with both genetic and autoimmune factors
Describe plaque psoriasis pathology
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
What is first line treatment for plaque psoriasis?
Suppress immune system & decrease inflammation:
Topical - steroids, tar products, Vit D
Systemically - methotrexate, cyclosporin
__________ is a TNF alpha blocking monoclonal antibody used to treat plaque psoriasis
Adalimumab (Humira)
________ was the first TNF alpha blocking monoclonal antibody used to treat plaque psoriasis
Infliximab (Remicade) 1998
How is adalimumab (Humira) administered and what are common side effects? (Plaque Psoriasis)
Bi-monthly injections
SA - injection site reactions, increased risk of infection
Less common - lymphoma, cytopenia, reactivation of TB
How is Infliximab (remicade) administered and what are common side effects? (Psoriasis TX)
Infusions every 6-8 weeks
SA - respiratory infections, HA, cough, infusion reactions
Less common - lupus-like syndromes, infections, malignancies
What are the two newer Psoriasis Treatments?
Ixekizumab (Taltz) and Ustekinumab (Stelara)
How is Ixekizumab (Taltz) (Psoriasis TX) administered and what are common side effects?
Injection every 2-4 weeks
Less SA - low risk of infection (herpes, candida), better clinical results over years
Ixekizumab (Taltz) MOA?
IL-17A high affinity, inhibitory monoclonal antibody
Ustekinumab (Stelara) MOA?
(Psoriasis TX)
IL-12 and IL-23 inhibitory monoclonal antibody
How is Ustekinumab (Stelara) administered and what are the SA?
Dosed by injection
Less SA - low risk of infection
Approved for use in other inflammatory conditions
