Abstract
Crohn's disease is characterized by acute and chronic intestinal inflammation, and can involve any part of the gastrointestinal tract. The most frequently involved areas of the intestine (the terminal ileum and colon) have higher bacterial loads than the rest of the intestine, suggesting a role for a dysregulated immune response to luminal bacteria. Research into the pathogenesis of Crohn's disease using animal models supports a role for Th1-mediated immune responses, and inhibition of the generation of a Th1 response is known to prevent disease. Based on these observations, antitumor necrosis factor-α (anti-TNFα) therapies have been used to treat patients with Crohn's disease and more recently with ulcerative colitis. Certain anti-TNFα therapies, such as infliximab, have resulted in dramatic clinical responses in patients with Crohn 's disease. Other therapies such as etanercept, however, have not been effective. In this review we will discuss the different strategies that have been employed to inhibit TNFα and their relative merits. We will also address factors that predict response to therapy such as concurrent immunomodulators, high C-reactive protein expression, and polymorphisms in the Fcγ receptor.
| Original language | English |
|---|---|
| Pages (from-to) | 160-168 |
| Number of pages | 9 |
| Journal | Current Opinion in Drug Discovery and Development |
| Volume | 8 |
| Issue number | 2 |
| State | Published - Mar 1 2005 |
| Externally published | Yes |
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Keywords
- Crohn's disease
- Etanercept
- Gastrointestinal
- Infliximab
- TNFα
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery
Cite this
Antibodies to tumor necrosis factor-α in the treatment of Crohn's disease. / Brown, Steven J.; Abreu, Maria T.
In: Current Opinion in Drug Discovery and Development, Vol. 8, No. 2, 01.03.2005, p. 160-168.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antibodies to tumor necrosis factor-α in the treatment of Crohn's disease
AU - Brown, Steven J.
AU - Abreu, Maria T
PY - 2005/3/1
Y1 - 2005/3/1
N2 - Crohn's disease is characterized by acute and chronic intestinal inflammation, and can involve any part of the gastrointestinal tract. The most frequently involved areas of the intestine (the terminal ileum and colon) have higher bacterial loads than the rest of the intestine, suggesting a role for a dysregulated immune response to luminal bacteria. Research into the pathogenesis of Crohn's disease using animal models supports a role for Th1-mediated immune responses, and inhibition of the generation of a Th1 response is known to prevent disease. Based on these observations, antitumor necrosis factor-α (anti-TNFα) therapies have been used to treat patients with Crohn's disease and more recently with ulcerative colitis. Certain anti-TNFα therapies, such as infliximab, have resulted in dramatic clinical responses in patients with Crohn 's disease. Other therapies such as etanercept, however, have not been effective. In this review we will discuss the different strategies that have been employed to inhibit TNFα and their relative merits. We will also address factors that predict response to therapy such as concurrent immunomodulators, high C-reactive protein expression, and polymorphisms in the Fcγ receptor.
AB - Crohn's disease is characterized by acute and chronic intestinal inflammation, and can involve any part of the gastrointestinal tract. The most frequently involved areas of the intestine (the terminal ileum and colon) have higher bacterial loads than the rest of the intestine, suggesting a role for a dysregulated immune response to luminal bacteria. Research into the pathogenesis of Crohn's disease using animal models supports a role for Th1-mediated immune responses, and inhibition of the generation of a Th1 response is known to prevent disease. Based on these observations, antitumor necrosis factor-α (anti-TNFα) therapies have been used to treat patients with Crohn's disease and more recently with ulcerative colitis. Certain anti-TNFα therapies, such as infliximab, have resulted in dramatic clinical responses in patients with Crohn 's disease. Other therapies such as etanercept, however, have not been effective. In this review we will discuss the different strategies that have been employed to inhibit TNFα and their relative merits. We will also address factors that predict response to therapy such as concurrent immunomodulators, high C-reactive protein expression, and polymorphisms in the Fcγ receptor.
KW - Crohn's disease
KW - Etanercept
KW - Gastrointestinal
KW - Infliximab
KW - TNFα
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UR - http://www.scopus.com/inward/citedby.url?scp=14844311937&partnerID=8YFLogxK
M3 - Article
C2 - 15782540
AN - SCOPUS:14844311937
VL - 8
SP - 160
EP - 168
JO - Current Opinion in Drug Discovery and Development
JF - Current Opinion in Drug Discovery and Development
SN - 1367-6733
IS - 2
ER -