Biomarkers of Anti-TNF Treatment in Inflammatory Bowel Disease (IBD)

NCT01971970 | Completed Results

• 1 other identifier: NL-42736.078.13
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-TNF treatment (infliximab (IFX), adalimumab (ADA)) has become standard therapy for refractory pediatric and adult Crohn's 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 adults.During 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.

Conditions

Inflammatory Bowel Diseases

Keywords

Inflammatory bowel disease; Pediatric; Adult; Biomarker; Anti-TNF response; Infliximab; Adalimumab

Outcome Measures

Primary Outcomes (2)

• Pre-treatment Serum Level of Endogenous Anti-TNF in Relation to Primary Clinical Response or Non-response

  Pre-treatment serum level of endogenous anti-TNF are measured and analyzed in relation to primary clinical response or non-response

  8 weeks

• RNA Expression Profiles in Relation to Clinical Endpoints

  Changes in week 0 and week 8 RNA expression profiles were evaluated in relation to the overall population and by study arm, i.e. either pediatric IBD or adult IBD.

  8 weeks

Secondary Outcomes (3)

• Number of Participants With Clinical Endpoints of Interest.

  Duration of study (start anti-TNF until 1 year after start of anti-TNF)

• Anti-TNF Treatment Specific Outcomes

  Duration of study (start anti-TNF until 1 year after start of anti-TNF)

• Number of Participants With Concommitant Treatment

  Duration of study (start anti-TNF until 1 year after start of anti-TNF)

Study Arms (2)

Pediatric IBD patients

Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab

Biological: Infliximab; Biological: Adalimumab

Adult IBD patients

Anti-TNF naive patients with either Crohn's disease or ulcerative colitis will be treated with either Infliximab or Adalimumab

Biological: Infliximab; Biological: Adalimumab

Interventions

Infliximab BIOLOGICAL

Remission induction in anti-TNF naïve patients will be achieved by administration of 5 mg/kg IFX infusions at week 0, 2 and 6.

Also known as: Remicade

Adult IBD patients; Pediatric IBD patients

Adalimumab BIOLOGICAL

ADA is administered as subcutaneous injections every other week.In children (age below 18 years), remission induction in anti-TNF naïve patients will be achieved by an initial loading dose of 80 mg, followed by 40 mg 2 weeks later. In adults, remission is induced by 160 mg at week 0, followed by 80 mg at week 2

Also known as: Humira

Adult IBD patients; Pediatric IBD patients

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Pediatric and adult IBD patients from the Department of Pediatric Gastroenterology of Erasmus MC-Sophia Children's Hospital and from the Department of Gastroenterology of Erasmus MC respectively.

You may qualify if:

• Anti-TNF naïve CD patients (≥ 6 years) who initiate anti-TNF treatment (IFX or ADA) because of active luminal disease, failing treatment with immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) and corticosteroids.
• Anti-TNF naïve UC patients (≥ 6 years) who initiate anti-TNF treatment (IFX or ADA) because of active disease despite corticosteroid treatment or because of failing of immunomodulator treatment.
• Anti-TNF naïve CD or UC patients (≥ 6 years) who initiate anti-TNF treatment (IFX or ADA) because of intolerance to treatment with immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) or corticosteroids.
• Informed consent by patients and parents (when required).

You may not qualify if:

• IBD patients who initiate IFX or ADA immediately after diagnosis.
• Presence of severe perianal disease as primary indication to start anti-TNF treatment.
• Age \< 6 years when anti-TNF maintenance treatment is initiated.

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Erasmus Medical Center

Rotterdam, 3015 GJ, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, gastrointestinal tract biopsies,buccal epithelium

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

Infliximab; Adalimumab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Limitations and Caveats

Further analysis of clinical endpoints in relation to (clinical) biomarkers will be done by Mixed Model Analysis

Results Point of Contact

• Title: Professor J.C. Escher
• Organization: Erasmus University Medical Centre - Sophia Childrens Hospital

j.escher@erasmusmc.nl

+31107036076

Study Officials

• J C Escher, MD, PhD

  Erasmus Medical Center - Sophia Children's Hospital

  PRINCIPAL INVESTIGATOR

• C J van der Woude, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: October 30, 2013
• Study Start: October 1, 2013
• Primary Completion: October 30, 2016
• Study Completion: January 30, 2017
• Last Updated: January 27, 2022
• Results First Posted: January 27, 2022

Record last verified: 2021-11

Locations

NL (1)