2/18
Which of the following agents is not a TNF-alpha inhibitor?
Which of the following agents is not a TNF-alpha inhibitor?
3/18
TNF-alpha inhibitors were initially developed for sepsis and underwent studies in animal models. After successful results in patients with rheumatoid arthritis, these agents have been widely evaluated in other chronic inflammatory diseases.
ncbi.nlm.nih.gov/books/NBK48242…
TNF-alpha inhibitors were initially developed for sepsis and underwent studies in animal models. After successful results in patients with rheumatoid arthritis, these agents have been widely evaluated in other chronic inflammatory diseases.
ncbi.nlm.nih.gov/books/NBK48242…
4/18
A meta-analysis showed that the use of TNF-alpha inhibitors was associated to an increased risk of tuberculosis (OR: 1.94; P=0.02), especially in patients receiving treatment for rheumatoid arthritis
bmjopen.bmj.com/content/7/3/e0…
A meta-analysis showed that the use of TNF-alpha inhibitors was associated to an increased risk of tuberculosis (OR: 1.94; P=0.02), especially in patients receiving treatment for rheumatoid arthritis
bmjopen.bmj.com/content/7/3/e0…
5/18
TNF-a is mostly secreted by macrophages and monocytes. It is essential for innate and adaptive immunity, promoting the production of inflammatory cytokines and enhancing the adhesion and recruitment of immune cells. It may also induce cell apoptosis and necrosis.
TNF-a is mostly secreted by macrophages and monocytes. It is essential for innate and adaptive immunity, promoting the production of inflammatory cytokines and enhancing the adhesion and recruitment of immune cells. It may also induce cell apoptosis and necrosis.
6/18
TNF-a is vital for acute and chronic inflammatory responses, such as chronic infections and autoimmunity. Signaling through TNFR1 results in a pro-inflammatory state, whereas signaling through TNFR2 causes immunomodulation and tissue regeneration. frontiersin.org/articles/10.33…
TNF-a is vital for acute and chronic inflammatory responses, such as chronic infections and autoimmunity. Signaling through TNFR1 results in a pro-inflammatory state, whereas signaling through TNFR2 causes immunomodulation and tissue regeneration. frontiersin.org/articles/10.33…
7/18
Cell-mediated immunity is essential for controlling TB. CD8 T cells limit TB growth by destroying infected cells and secreting cytokines to activate macrophages. CD8 T cells are crucial for the chronic containment of TB, avoiding reactivation of LTBI. ncbi.nlm.nih.gov/pmc/articles/P…
Cell-mediated immunity is essential for controlling TB. CD8 T cells limit TB growth by destroying infected cells and secreting cytokines to activate macrophages. CD8 T cells are crucial for the chronic containment of TB, avoiding reactivation of LTBI. ncbi.nlm.nih.gov/pmc/articles/P…
8/18
In TB, TNF-a is produced by epithelial airway cells, CD8 T cells, and activated macrophages. TNF-a stimulates the production of chemokines to attract immune cells to the site of infection, and increases the production of nitric oxide in macrophages.
frontiersin.org/articles/10.33…
In TB, TNF-a is produced by epithelial airway cells, CD8 T cells, and activated macrophages. TNF-a stimulates the production of chemokines to attract immune cells to the site of infection, and increases the production of nitric oxide in macrophages.
frontiersin.org/articles/10.33…
9/18
TNF-a is critical for the formation and maintenance of granulomas to contain TB. Activated macrophages within the granuloma secrete IL-6 and TNF-a, which favor inflammation, and IL-10, which modulates inflammatory responses
frontiersin.org/articles/10.33…
TNF-a is critical for the formation and maintenance of granulomas to contain TB. Activated macrophages within the granuloma secrete IL-6 and TNF-a, which favor inflammation, and IL-10, which modulates inflammatory responses
frontiersin.org/articles/10.33…
10/18
Depletion of CD45RA+ effector memory T cells (TEMRA) has been proposed as a contributor to TB reactivation. TEMRA from patients with RA have high levels of membrane-bound TNF and could suffer complement-mediated lysis after exposure to infliximab.
ncbi.nlm.nih.gov/pmc/articles/P…
Depletion of CD45RA+ effector memory T cells (TEMRA) has been proposed as a contributor to TB reactivation. TEMRA from patients with RA have high levels of membrane-bound TNF and could suffer complement-mediated lysis after exposure to infliximab.
ncbi.nlm.nih.gov/pmc/articles/P…
11/18
Also, TNF-a inhibitors can interfere with phagolysosomal maturation, monocyte apoptosis, IFN secretion by memory T cells, and in the complement-mediated lysis of infected cells mediated by CD8 T cells, which are critical for TB containment.
ncbi.nlm.nih.gov/pmc/articles/P…
Also, TNF-a inhibitors can interfere with phagolysosomal maturation, monocyte apoptosis, IFN secretion by memory T cells, and in the complement-mediated lysis of infected cells mediated by CD8 T cells, which are critical for TB containment.
ncbi.nlm.nih.gov/pmc/articles/P…
12/18
Which of the following TNF-alpha inhibitors is less frequently associated with TB reactivation?
Which of the following TNF-alpha inhibitors is less frequently associated with TB reactivation?
13/18
Etanercept is a soluble fusion protein, not a monoclonal antibody. A reduced penetration into granulomas has been reported. As it binds less to membrane-bound TNF, TEMRA depletion might be less prominent. Differences could explain the lower TB rate.
academic.oup.com/jid/article/19…
Etanercept is a soluble fusion protein, not a monoclonal antibody. A reduced penetration into granulomas has been reported. As it binds less to membrane-bound TNF, TEMRA depletion might be less prominent. Differences could explain the lower TB rate.
academic.oup.com/jid/article/19…
14/18
Strategies applied to screen and treat LTBI in patients receiving TNF-a inhibitors are highly-effective. In Spain, after implementing guidelines and a national patient registry, the rate of active TB in patients receiving infliximab dropped by 74%
onlinelibrary.wiley.com/doi/full/10.10…
Strategies applied to screen and treat LTBI in patients receiving TNF-a inhibitors are highly-effective. In Spain, after implementing guidelines and a national patient registry, the rate of active TB in patients receiving infliximab dropped by 74%
onlinelibrary.wiley.com/doi/full/10.10…
15/18
All patients receiving TNF-a inhibitors should be tested for LTBI. It can be assessed through tuberculin skin testing (TST) and Interferon-γ release assays (IGRAs). Repeated testing in 1-3 weeks could be considered if results are initially negative
onlinelibrary.wiley.com/doi/full/10.10…
All patients receiving TNF-a inhibitors should be tested for LTBI. It can be assessed through tuberculin skin testing (TST) and Interferon-γ release assays (IGRAs). Repeated testing in 1-3 weeks could be considered if results are initially negative
onlinelibrary.wiley.com/doi/full/10.10…
16/18
TST consists of injecting TB purified protein derivatives in the forearm. In exposed individuals, a type IV hypersensitivity reaction produces skin induration that is measured 24-72 hours later. It is less specific, as other mycobacteria (BCG) might cause false positives
TST consists of injecting TB purified protein derivatives in the forearm. In exposed individuals, a type IV hypersensitivity reaction produces skin induration that is measured 24-72 hours later. It is less specific, as other mycobacteria (BCG) might cause false positives
17/18
Interferon-γ release assays (IGRAs) assess in vitro T cell response against specific M tuberculosis antigens. It is more specific as antigens are not found in BGC or other non-TB mycobacteria. IGRAs are more expensive and less accessible.
nejm.org/doi/full/10.10…
Interferon-γ release assays (IGRAs) assess in vitro T cell response against specific M tuberculosis antigens. It is more specific as antigens are not found in BGC or other non-TB mycobacteria. IGRAs are more expensive and less accessible.
nejm.org/doi/full/10.10…
18/18
All patients treated with TNF-a inhibitors, with a positive LTBI screening and no evidence of active TB infection, should be treated accordingly. Recommended regimens to treat LTBI are described below.
cdc.gov/mmwr/volumes/6…
All patients treated with TNF-a inhibitors, with a positive LTBI screening and no evidence of active TB infection, should be treated accordingly. Recommended regimens to treat LTBI are described below.
cdc.gov/mmwr/volumes/6…
