Clinical Outcome After Escalation and De-escalation of Adalimumab in Real Life in Ulcerative Colitis (CEDAR UC)

October 25, 2017 updated by: Universitaire Ziekenhuizen KU Leuven

A Retrospective Multicentric Belgian Observational Trial to Evaluate the Successfulness of Adalimumab Dose Escalation and De-escalation in Patients With Moderate-to-severe Ulcerative Colitis Treated With Adalimumab

This retrospective multi-centric Belgian observational trial will involve all patients who have initiated adalimumab for moderate-to-severe ulcerative colitis prior to September 1st 2015 in a Belgian centre maintaining a prospective log of patients using biological therapy.

Only patients fulfilling all Belgian reimbursement criteria for adalimumab will be included, namely having failed mesalamine and steroids or thiopurine analogues for at least 3 months, or being intolerant to this therapy, and showing a total Mayo score of at least 6 with an endoscopic sub-score of at least 2.

Both short-term and long-term outcome of adalimumab therapy will be evaluated, focusing on the need and successfulness of adalimumab dose-escalation from 40mg every other week to 40mg every week, and dose de-escalation back to 40mg every other week.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Adalimumab is approved for the treatment of moderate to severe ulcerative colitis after failure of aminosalicylates plus corticosteroids and/or immunomodulators.1-4 In the registration studies for adalimumab in ulcerative colitis prior anti-tumor necrosis factor (TNF) treatment was restricted; in ULTRA 1, prior anti-TNF treatment was an exclusion criterion,5 while in ULTRA 2, 40% of patients had been exposed to infliximab prior to start of adalimumab, but primary non-responders to infliximab were excluded.6 Open label real life studies have shown good responses to adalimumab in UC. However typically, these cohorts were small and most patients were anti-TNF naïve. One Italian open label study on 88 patients reported clinical remission rates of 28% and 43% at week 12 and year 1, respectively.7 No significant differences were observed between infliximab naïve and infliximab exposed UC patients. In a Belgian open label study of 73 patients previously failing infliximab, overall clinical response at week 12 and 52 were 75% and 52%, respectively.8 Adalimumab was continued without need for dose escalation throughout year 1 in 16 patients, 22 needed dose escalation and 35 discontinued treatment within 1 year. Prior response to infliximab and early serum concentrations correlated with response.

While data are available in Crohn's disease,9 real life data on adalimumab dose escalation and dose de-escalation are limited in ulcerative colitis. Similarly, factors associated with need and success of dose escalation and dose de-escalation later on are almost absent.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
231

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium
        • University Hospitals Leuven

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study will enrol all subjects who initiated adalimumab for moderate-to-severe ulcerative colitis before September 1st 2015 at 11 sites throughout Belgium. These 11 sites have pre-screened their database, and almost 300 patients seem eligible.

Description

Site Selection:

  • Only Belgian sites are eligible
  • Participating sites must maintain a patient log allowing a full coverage of patients eligible for this study
  • Membership of the Belgian IBD Research and Development (BIRD) group is not mandatory
  • Local investigator is willing and able to fill out a two page case report form (CRF) for each eligible patient in a two month period (deadline November 1st 2016)

Inclusion Criteria:

  • Age at least 18 at initiation of adalimumab therapy
  • Adalimumab initiated before September 1st 2015
  • Established diagnosis of ulcerative colitis
  • Having failed mesalamine and steroids or thiopurine analogues for at least 3 months, or being intolerant to this therapy (as described in the Belgian reimbursement criteria)
  • Active ulcerative colitis as described in the Belgian reimbursement criteria, namely showing a total Mayo score of at least 6 with an endoscopic sub-score of at least 2

Exclusion Criteria:

  • Subjects with Crohn's disease or inflammatory bowel disease (IBD) type unclassified
  • Subjects previously treated with adalimumab
  • Subjects treated with adalimumab for other reasons than moderate-to-severe ulcerative colitis, including extra-intestinal manifestations and pre-emptively switch from other biological therapies (i.e. while being in clinical remission)
  • Subjects who underwent subtotal colectomy or proctocolectomy prior to adalimumab initiation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The need and success of adalimumab dose escalation from 40mg every other week to 40mg every week in patients with moderate-to-severe ulcerative colitis during adalimumab treatment
Time Frame: Through study completion, an average of 24 months

The proportion of patients requiring dose-escalation from adalimumab 40mg every other week to 40mg every week and the success rate of this intervention.

Success of dose-escalation is defined based on a positive physician global assessment and absence of blood on two consecutive visits at least 3 months apart from each other. Of note: patients requiring a second intervention later on (addition of any type of steroids, addition of any immunomodulatory drug or optimization to off-label adalimumab 80 mg every week) will be regarded as failure (treatment optimization based on trough level monitoring or biomarkers alone will not be included)
Through study completion, an average of 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Short-term (steroid-free) clinical response response to adalimumab in patients with moderate-to-severe ulcerative colitis
Time Frame: Week 8
Short-term clinical response is defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the sub-score for rectal bleeding of at least 1 point or an absolute rectal-bleeding sub-score of 0 or 1
Week 8
Short-term (steroid-free) clinical remission response to adalimumab in patients with moderate-to-severe ulcerative colitis
Time Frame: Week 8
Short-term clinical remission is defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point
Week 8
Short-term (steroid-free) clinical benefit to adalimumab in patients with moderate-to-severe ulcerative colitis
Time Frame: Week 8
Short-term clinical benefit is defined as a meaningful clinical response with clear improvement in symptoms at discretion of the physician
Week 8
Short-term (steroid-free) mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis
Time Frame: Week 8
Short-term mucosal healing is defined as a Mayo endoscopic sub-score of 0 or 1 at lower endoscopy performed between week 8 and 14
Week 8
Short-term (steroid-free) complete mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis
Time Frame: Week 8
Short-term complete mucosal healing is defined as a Mayo endoscopic sub-score of 0 at lower endoscopy performed between week 8 and 14
Week 8
Short-term (steroid-free) biological response to adalimumab in patients with moderate-to-severe ulcerative colitis
Time Frame: Week 8
Short-term biological response is defined as a normalization of C-reactive protein (CRP) to <5 mg/L in patients with an elevated CRP at baseline (≥5 mg/L) and/or a normalization of faecal calprotectin to <250µg/g in patients with an elevated faecal calprotectin at baseline (≥250 µg/g)
Week 8
Adalimumab dose-escalation free survival during adalimumab treatment
Time Frame: Through study completion, an average of 24 months
Adalimumab dose-escalation free survival during adalimumab treatment
Through study completion, an average of 24 months
Adalimumab dose de-escalation free survival during adalimumab treatment
Time Frame: Through study completion, an average of 24 months
Adalimumab dose de-escalation free survival during adalimumab treatment
Through study completion, an average of 24 months
Success of dose de-escalation within 6 months after dose de-escalation
Time Frame: Through study completion, an average of 24 months
Success of dose de-escalation is defined as a persistent use of adalimumab at a dose of 40mg every other week for at least 6 months after dose de-escalation
Through study completion, an average of 24 months
Safety of adalimumab: Proportion of patients developing (serious) adverse events under adalimumab therapy during adalimumab treatment
Time Frame: Through study completion, an average of 24 months
Proportion of patients developing (serious) adverse events under adalimumab therapy during adalimumab treatment
Through study completion, an average of 24 months
UC related hospitalization during adalimumab treatment
Time Frame: Through study completion, an average of 24 months
Proportion of patient requiring ulcerative colitis related hospitalization during adalimumab treatment
Through study completion, an average of 24 months
UC related colectomy during follow-up
Time Frame: Through study completion, an average of 24 months
Proportion of patient requiring colectomy during follow-up
Through study completion, an average of 24 months
Identification of variables associated with short-term outcome
Time Frame: Week 8
Identifying variables associated with short-term outcome adalimumab
Week 8
Identification of baseline variables associated with need for dose-escalation
Time Frame: Through study completion, an average of 24 months
Identifying variables associated with need of dose escalation to adalimumab 40mg every week; variables to be evaluated will include sex, age, disease duration, familial history, extent of disease, previous medical therapy, concomitant medical therapy, adalimumab induction scheme, baseline serum values (Hb, albumin, CRP, ...), baseline endoscopic evaluation
Through study completion, an average of 24 months
Identification of baseline variables associated with successful dose-escalation
Time Frame: Through study completion, an average of 24 months
Identifying variables associated with success of dose escalation to adalimumab 40mg every week; variables to be evaluated will include sex, age, disease duration, familial history, extent of disease, previous medical therapy, concomitant medical therapy, adalimumab induction scheme, baseline serum values (Hb, albumin, CRP, ...), baseline endoscopic evaluation
Through study completion, an average of 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universitaire Ziekenhuizen KU Leuven

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Liege
University Hospital, Ghent
Imelda Hospital, Bonheiden
AZ Delta
General Hospital Groeninge
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Université Catholique de Louvain
Algemeen Ziekenhuis Maria Middelares
Onze Lieve Vrouwziekenhuis Aalst
Centre Hospitalier Universitaire Dinant Godinne - UCL Namur
Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marc Ferrante, MD PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 26, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 2, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 5, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 26, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • S59663

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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