Clinical Outcome After Escalation and De-escalation of Adalimumab in Real Life in Ulcerative Colitis

NCT ID: NCT03142113

Last Updated: 2017-10-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 231 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2017-05-31

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.

Conditions

Ulcerative Colitis

Keywords

optimization; adalimumab

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• 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)

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

OTHER

Sponsor Role: collaborator

Imelda Hospital, Bonheiden

OTHER

Sponsor Role: collaborator

University of Liege

OTHER

Sponsor Role: collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

AZ Delta

OTHER

Sponsor Role: collaborator

Algemeen Ziekenhuis Maria Middelares

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: collaborator

General Hospital Groeninge

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire UCLouvain Namur

OTHER

Sponsor Role: collaborator

Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

Onze Lieve Vrouwziekenhuis Aalst

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Ferrante, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Locations

University Hospitals Leuven

Leuven, , Belgium

Countries

Belgium

Other Identifiers

S59663

Identifier Type: -

Identifier Source: org_study_id