Ignite Creation Date:
2024-05-06 @ 2:09 AM
Last Modification Date:
2024-10-26 @ 11:14 AM
Study NCT ID:
NCT01971970
Status:
COMPLETED
Last Update Posted:
2022-01-27
First Post:
2013-10-24
Brief Title:
Biomarkers of Anti-TNF Treatment in Inflammatory Bowel Disease IBD
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Biomarkers Predicting the Effect of Anti-TNF Treatment in Pediatric and Adult Inflammatory Bowel Disease
Status:
COMPLETED
Status Verified Date:
2021-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Anti-TNF treatment infliximab IFX adalimumab ADA has become standard therapy for refractory pediatric and adult Crohns disease CD patients and is used for the induction primary response and maintenance of remission When effective clinical and endoscopic remission is reached within weeks However primary non-response is observed in 20 of pediatric patients and in 40 of adult CD patients suggesting a more robust acute response to anti-TNF therapy in children as compared to adultsDuring maintenance treatment 60 - 80 of patients have secondary loss of response necessitating dose adjustments to maintain clinical response Anti-TNF treatment is also increasingly used in ulcerative colitis UC and has been shown to induce remission in active disease For UC the comparison between the efficacy in children versus adults is more difficult to report as studies in children are scarce Anti-TNF treatment is associated with rare but potentially fatal side effects infusion reactions and is an expensive treatment To avoid overtreatment it is necessary to early identify non-responders to treatment and therefore it is important to develop predictive biomarkers of treatment response
Detailed Description:
Crohns disease CD is a lifelong disease that may present during childhood in 20 - 25 of patients There seems to be a worldwide trend towards increasing incidence rates of CD especially in children Patients with CD suffer from diarrhea abdominal pain nausea malaise and chronic malnutrition in children often accompanied by growth failure and pubertal delay CD is characterized by a transmural granulomatous inflammation involving any part of the gastrointestinal tract in a discontinuous manner
Increased concentrations of tumor necrosis factor-α TNFα are found in the mucosa of CD patients suggesting that TNF-α plays a pivotal role in the cytokine cascade of the inflammatory process This key role of TNF-α has led to the development of biologic therapy based on the administration of monoclonal antibodies which bind and inactivate TNF-α Infliximab IFX Remicade is a chimeric monoclonal antibody 75 human 25 murine while adalimumab ADA Humira is a fully human monoclonal antibody Both antibodies bind with high affinity and specificity to soluble and membrane-bound TNF-α
Anti-TNF drugs have become an important treatment strategy for CD patients who do not respond to or are intolerant of treatment with immunosuppressants azathioprine methotrexate and corticosteroids Anti-TNF induction therapy can induce complete clinical remission within weeks often accompanied by mucosal healing Interestingly response to initial anti-TNF treatment is higher in pediatric CD patients about 80 than in adult CD patients about 60 Anti-TNF drugs do not cure CD after their impressive initial effects repeated infusions every 8 weeks or repeated subcutaneous injections every 2 weeks are necessary while there is great concern about the long-term risks infections auto-immune disease malignancy Anti-TNF treatment is also increasingly used in ulcerative colitis and has been shown to induce remission in active disease For UC the comparison between the efficacy in children versus adults is more difficult to report as studies in children are scarce There are likely multiple host factors that influence the inter-individual variation in initial treatment response such as disease phenotype immune phenotype and genetic background
Increased concentrations of tumor necrosis factor-α TNFα are found in the mucosa of CD patients suggesting that TNF-α plays a pivotal role in the cytokine cascade of the inflammatory process This key role of TNF-α has led to the development of biologic therapy based on the administration of monoclonal antibodies which bind and inactivate TNF-α Infliximab IFX Remicade is a chimeric monoclonal antibody 75 human 25 murine while adalimumab ADA Humira is a fully human monoclonal antibody Both antibodies bind with high affinity and specificity to soluble and membrane-bound TNF-α
Anti-TNF drugs have become an important treatment strategy for CD patients who do not respond to or are intolerant of treatment with immunosuppressants azathioprine methotrexate and corticosteroids Anti-TNF induction therapy can induce complete clinical remission within weeks often accompanied by mucosal healing Interestingly response to initial anti-TNF treatment is higher in pediatric CD patients about 80 than in adult CD patients about 60 Anti-TNF drugs do not cure CD after their impressive initial effects repeated infusions every 8 weeks or repeated subcutaneous injections every 2 weeks are necessary while there is great concern about the long-term risks infections auto-immune disease malignancy Anti-TNF treatment is also increasingly used in ulcerative colitis and has been shown to induce remission in active disease For UC the comparison between the efficacy in children versus adults is more difficult to report as studies in children are scarce There are likely multiple host factors that influence the inter-individual variation in initial treatment response such as disease phenotype immune phenotype and genetic background
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None