Ulcerative ColitisCEDAR UCNCT03142113
Clinical Outcome After Escalation and De-escalation of Adalimumab in Real Life in Ulcerative Colitis
An observational study of Ulcerative Colitis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- How many people
- 231 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2016to May 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Keywords
- optimization, adalimumab
- Medical subject headings
- Colitis, Ulcerative
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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)
Measured: Through study completion, an average of 24 months
Secondary outcomes (15)
Short-term (steroid-free) clinical response response to adalimumab in patients with moderate-to-severe ulcerative colitis
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
Measured: Week 8
Short-term (steroid-free) clinical remission response to adalimumab in patients with moderate-to-severe ulcerative colitis
Short-term clinical remission is defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point
Measured: Week 8
Short-term (steroid-free) clinical benefit to adalimumab in patients with moderate-to-severe ulcerative colitis
Short-term clinical benefit is defined as a meaningful clinical response with clear improvement in symptoms at discretion of the physician
Measured: Week 8
Short-term (steroid-free) mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis
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
Measured: Week 8
Short-term (steroid-free) complete mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis
Short-term complete mucosal healing is defined as a Mayo endoscopic sub-score of 0 at lower endoscopy performed between week 8 and 14
Measured: Week 8
Short-term (steroid-free) biological response to adalimumab in patients with moderate-to-severe ulcerative colitis
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)
Measured: Week 8
Adalimumab dose-escalation free survival during adalimumab treatment
Adalimumab dose-escalation free survival during adalimumab treatment
Measured: Through study completion, an average of 24 months
Adalimumab dose de-escalation free survival during adalimumab treatment
Adalimumab dose de-escalation free survival during adalimumab treatment
Measured: Through study completion, an average of 24 months
Success of dose de-escalation within 6 months after dose de-escalation
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
Measured: Through study completion, an average of 24 months
Safety of adalimumab: Proportion of patients developing (serious) adverse events under adalimumab therapy during adalimumab treatment
Proportion of patients developing (serious) adverse events under adalimumab therapy during adalimumab treatment
Measured: Through study completion, an average of 24 months
UC related hospitalization during adalimumab treatment
Proportion of patient requiring ulcerative colitis related hospitalization during adalimumab treatment
Measured: Through study completion, an average of 24 months
UC related colectomy during follow-up
Proportion of patient requiring colectomy during follow-up
Measured: Through study completion, an average of 24 months
Identification of variables associated with short-term outcome
Identifying variables associated with short-term outcome adalimumab
Measured: Week 8
Identification of baseline variables associated with need for dose-escalation
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
Measured: Through study completion, an average of 24 months
Identification of baseline variables associated with successful dose-escalation
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
Measured: Through study completion, an average of 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2017
- Study startNov 2016
- Primary completionDec 2016
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 231 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW, Imelda Hospital, Bonheiden, University of Liege, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, AZ Delta, Algemeen Ziekenhuis Maria Middelares, University Hospital, Ghent, General Hospital Groeninge, Centre Hospitalier Universitaire UCLouvain Namur, Université Catholique de Louvain, Onze Lieve Vrouwziekenhuis Aalst
- Responsible party
- Sponsor
- Investigators
- Marc Ferrante, MD PhD, Principal investigator, Universitaire Ziekenhuizen KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03142113
- Sponsor's protocol ID
- S59663
- Acronym
- CEDAR UC
- Status last verified
- Oct 2017
- First submitted
- 26 Oct 2016
- Last updated
- 26 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03142113
- Acronym / sponsor ID
- CEDAR UC / S59663
- Conditions
- Ulcerative Colitis
- Keywords
- optimization, adalimumab
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 231 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW, Imelda Hospital, Bonheiden, University of Liege, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, AZ Delta, Algemeen Ziekenhuis Maria Middelares, University Hospital, Ghent, General Hospital Groeninge, Centre Hospitalier Universitaire UCLouvain Namur, Université Catholique de Louvain, Onze Lieve Vrouwziekenhuis Aalst
- Study start
- Nov 2016
- Primary completion
- Dec 2016 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 5 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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)
15 secondary outcomes
Short-term (steroid-free) clinical response response to adalimumab in patients with moderate-to-severe ulcerative colitis
Time frame: 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 (steroid-free) clinical benefit to adalimumab in patients with moderate-to-severe ulcerative colitis
Time frame: Week 8
Short-term (steroid-free) mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis
Time frame: 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 (steroid-free) biological response to adalimumab in patients with moderate-to-severe ulcerative colitis
Time frame: Week 8
Adalimumab dose-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
Time frame: 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
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
UC related hospitalization during adalimumab treatment
Time frame: Through study completion, an average of 24 months
UC related colectomy during follow-up
Time frame: Through study completion, an average of 24 months
Identification of variables associated with short-term outcome
Time frame: Week 8
Identification of baseline variables associated with need for dose-escalation
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Ferrante, MD PhD principal investigator
Universitaire Ziekenhuizen KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ulcerative Colitis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2017.