Anti-TNF-alpha Trough Level Measurements in Inflammatory Bowel Disease

Drug serum concentrations will be measured at several time-points for inflammatory disease patients treated with anti-TNF agents. The purpose is to determine which patients that will clinically benefit from either discontinue treatment, adjusting the dose, switch to another anti-TNF agent or a different class of medication.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease; Ulcerative Colitis; Inflammatory Bowel Disease
• Intervention / Treatment: Drug: Infliximab, adalimumab, certolizumab pegol

Detailed Description

Crohn´s disease and ulcerative colitis are diseases where the proinflammatory cytokine Tumor Necrosis Factor-alpha (TNF) plays an important role. Anti-TNF agents are used in the treatment. However, some patients do not respond and response rates declines over time. The cause may be immunogenicity against the agent itself, the agent´s failure to neutralize TNF or another biological pathway leading to inflammation. Anti-TNF agents have been administrated as fixed doses at certain frequencies and this may not be optimal for all patients, but recent studies have indicated a correlation between efficacy and serum drug concentration levels (trough levels). Our preliminary data suggest that trough levels early in the treatment course may be predictive of later trough levels. By multiple measurements, this will be assessed. The study will also investigate biological markers in serum and blood cells which may be predictable for trough levels. Finally, we will compare different methods to measure serum drug concentrations.

• Study Type: Observational
• Enrollment (Actual): 1230

Contacts and Locations

Study Locations

• Norway
  • Postboks PB 4950 Nydalen
    • Oslo, Postboks PB 4950 Nydalen, Norway, 0424
      • Rikshospitalet-Radiumhospitalet HF, Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Inflammatory bowel disease treated with anti-TNF drug

Description

Inclusion Criteria:

• Patients diagnosed with Inflammatory bowel disease
• Treated with anti-TNF drug
• Follow-up at specialized gastroenterologist in Norway
• Age 18 or over

Exclusion Criteria:

• Patients refusing to participate by not giving their informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Anti-TNF; Inflammatory bowel patients age 18 and over treated with anti-TNF agents	Drug: Infliximab, adalimumab, certolizumab pegol; Patients are treated with the above mentioned drugs decided by clinicians

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of drug serum concentrations	Drug serum concentration will be measured using an ELISA	Serum samples will be collected on average 8 weeks (range 0-90 days) after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure soluble TNF-receptor in serum		Measurement will be conducted in 2015 on blood samples stored in a bio-bank
Assay validation	Drug concentration measurements will be conducted with ELISA's with monoclonal and polyclonal antibodies, automated immunofluorometric assay and commercial kits for the purpose to validate tests and establish standards for measurements	December 2013 - March 2014
Change in individuals drug serum concentration	Intra-individual fluctuations in consecutively measurements during a course of treatment will be measured.	Serum samples will be collected on average 8 weeks (range 0-90 days) after drug administration

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Knut EA Lundin, Prof., Oslo University Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: January 9, 2014
• First Submitted That Met QC Criteria: February 25, 2014
• First Posted (Estimate): February 27, 2014

Study Record Updates

• Last Update Posted (Estimate): December 6, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Anti-TNF; Antibodies, Monoclonal; TNF-alpha; Drug concentration; ELISA; Trough level
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Adalimumab; Infliximab; Certolizumab Pegol
• Other Study ID Numbers: 2013-1352