Clinical trial NCT03142113: Clinical Outcome After Escalation and De-escalation of Adalimumab in Real Life in Ulcerative Colitis
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ulcerative Colitis
Keywords: optimization
adalimumab
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
name: Imelda Hospital, Bonheiden
name: University of Liege
name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: AZ Delta
name: Algemeen Ziekenhuis Maria Middelares
name: University Hospital, Ghent
name: General Hospital Groeninge
name: Centre Hospitalier Universitaire UCLouvain Namur
name: Université Catholique de Louvain
name: Onze Lieve Vrouwziekenhuis Aalst
First posted: 2017-05-05
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
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
timeFrame: Through study completion, an average of 24 months
Secondary outcomes:
measure: Short-term (steroid-free) clinical response response to adalimumab in patients with moderate-to-severe ulcerative colitis
timeFrame: Week 8
measure: Short-term (steroid-free) clinical remission response to adalimumab in patients with moderate-to-severe ulcerative colitis
timeFrame: Week 8
measure: Short-term (steroid-free) clinical benefit to adalimumab in patients with moderate-to-severe ulcerative colitis
timeFrame: Week 8
measure: Short-term (steroid-free) mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis
timeFrame: Week 8
measure: Short-term (steroid-free) complete mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis
timeFrame: Week 8
measure: Short-term (steroid-free) biological response to adalimumab in patients with moderate-to-severe ulcerative colitis
timeFrame: Week 8
measure: Adalimumab dose-escalation free survival during adalimumab treatment
timeFrame: Through study completion, an average of 24 months
measure: Adalimumab dose de-escalation free survival during adalimumab treatment
timeFrame: Through study completion, an average of 24 months
measure: Success of dose de-escalation within 6 months after dose de-escalation
timeFrame: Through study completion, an average of 24 months
measure: Safety of adalimumab: Proportion of patients developing (serious) adverse events under adalimumab therapy during adalimumab treatment
timeFrame: Through study completion, an average of 24 months
measure: UC related hospitalization during adalimumab treatment
timeFrame: Through study completion, an average of 24 months
measure: UC related colectomy during follow-up
timeFrame: Through study completion, an average of 24 months
measure: Identification of variables associated with short-term outcome
timeFrame: Week 8
measure: Identification of baseline variables associated with need for dose-escalation
timeFrame: Through study completion, an average of 24 months
measure: Identification of baseline variables associated with successful dose-escalation
timeFrame: Through study completion, an average of 24 months
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Marc Ferrante, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: