Biologic response modifiers to decrease inflammation: focus on infection risks

Question 1

What are biologic response modifiers?

Answer 1

Antibodies to pro-inflammatory cytokines or proteins that target the cytokine receptors with a common net effect is a pro-inflammatory cytokine “inhibitor” effect, thus modifying the immune response

Question 2

What is abatacept?

Answer 2

Trade name Orencia binds to CD80 and CD86 on antigen presenting cells and blocks production of TNF-alpha, IL-2 and interferon-gamma. Selective costimulation modulator protein fused to human IgG

Question 3

What is adalimumab?

Answer 3

Trade name Humira. TNF antagonist. Humanized IgG1 monoclonal antibody

Question 4

What is anakinra?

Answer 4

Trade name Kineret. Binds to IL-1 alpha receptor. Human monoclonal antibody against IL-1.

Question 5

What is canakinumab?

Answer 5

Trade name Illaris. Binds to IL-1 beta receptor and prevents interaction of cell surface receptors. Monoclonal antibody against IL-1beta

Question 6

What is certolizumab?

Answer 6

Cimzia. TNF antagonist. Humanized PEGylated Fab’ of a TNF-alpha monoclonal antibody

Question 7

What is etanercept?

Answer 7

Enbrel. TNF antagonist. Soluble p75 TNF-alpha receptor fusion protein construct that binds to and inactivated TNF-alpha.

Question 8

What is golimumab?

Answer 8

Simponi. TNF antagonist. IgG1K with human variable regions.

Question 9

What is infliximab?

Answer 9

Remicade. TNF antagonist. Humanized IgG1K with murine variable regions

Question 10

What is natalizumab?

Answer 10

Tysabri. Blocks integrin association with vascular receptors limiting adhesion and transmigration of leukocytes. Monoclonal antibody against the alpha-4 subunit of integrin molecules.

Question 11

What is rilonacept?

Answer 11

Arcalyst. Binds to IL-1 alpha and beta and prevents interaction of cell surface receptors. IL-1 receptor fusion protein.

Question 12

What is tocilizumab?

Answer 12

Actemra. IL-6 receptor antagonist. Humanized monoclonal antibody.

Question 13

What is ustekinumab?

Answer 13

Stelara. IL-12 and IL-23 antagonist. Humanized monoclonal antibody

Question 14

How do BRM increase the risk of infection?

Answer 14

TNF alpha and other pro-inflammatory cytokines generate an inflammatory response important for:

1. T cell mediated immune responses for destruction of intracellular pathogens
2. Formation of granulomas
3. Ensure adequate cell mediated response

Question 15

What infections are increased in clinical settings?

Answer 15

1. Tuberculosis
2. Fungal infections o.e. Histoplasma capsulatum, Blastomyces dermatidis, Coccidioides immites
3. Non tuberculous mycobacterium
4. Intracellular bacreria i.e. Listeria monocytogenes
5. Reactivation of Strongyloides
6. Case reports of reactivation of chronic viral infection e.g. HSV, varicella, HBV

Question 16

What is the recommended patient work-up before initiation of BMR therapy?

Answer 16

1. TBST
2. CXR
3. Document vaccination status and ensure up to date
4. Administer all live virus vaccines a minimum of 4 weeks before initiation
5. Counsel household members regarding risk of disease and ensure vaccination for prevention of exposure to varicella and influenza and other transmissable infections
6. Depending on risk of past exposure, consider serology for Histoplasma, Toxoplasma, and other intracellular pathogens
7. Consider serology for HBV, varicella-zoster, and EBV
8. Counselling with respect to food safety
9. Couselling with respect to maintenance of dental hygiene
10. Counselling with respect to exposure to heavy concentrations of garden soils, pets, and other animals
11. Counselling with respect to high risk activities i.e. spelunking
12. Counselling with respect to travel to areas endemic for pathogenic fungi or to areas where TB is endemic

Question 17

What recommendations are there for food safety?

Answer 17

Avoid eating:

1. undercooked or deli meats
2. raw eggs
3. unpasteurized milk products incld. soft cheeses

Question 18

What other recommendations are there for avoiding infections?

Answer 18

Avoid direct contact w/

1. soil (T. gondii)
2. kitty litter (T. gondii)
3. kittens (Bartonella)
4. pet reptiles (Salmonella)
5. other pet bites or scratches (Pasteurella)
6. construction sites (fungal spores)
7. farmyard barns (fungal spores)
8. cave exploration (fungal spores)

Question 19

What are the recommendations regarding vaccination and BMR?

Answer 19

1. Pneumococcal vaccine: complete primary series if <59mo, if min. 24mo give pneumococcal polysaccharide vaccine 8wks after last dose of conjugate vaccine, if >59mo and primary series not complete give a dose of pneumococcal polysaccharide OR conjugate ten polysaccharide 8 wks later
2. Annual inactivated influenza vaccine
3. Complete routine inactivated immunizations 14d prior to starting BMR or 1m prior if on high dose steroids
4. Live vaccines can be given 4 wks prior to starting BMR
5. Live vaccines are contraindicated in patient on BMR