A Retrospective Observational Study to Assess the Impact of Co-morbidities on Treatment Response in Inflammatory Bowel Disease

Impact of Co-morbidities on Treatment Response in Inflammatory Bowel Disease: VERNE Study

The purpose of this study was to evaluate the impact of the co-morbidities profile on treatment response to biological therapy in inflammatory bowel disease (IBD) participants.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Other: No Intervention

Detailed Description

This was a retrospective, non-interventional, observational study that included participants diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who started treatment with biologics between June 2011 and June 2013. The study looked at the impact of the co-morbidities on the treatment response in IBD participants.

The study enrolled 310 patients included both UC and CD patients.

This multicenter trial was conducted in Spain. Investigator collected retrospective data in a single visit from participants who started biologic treatment between June 2011 and June 2013. Time since participants started biological treatment until study visit or until lack of treatment response or until treatment change constituted the reference period for the study.

• Study Type: Observational
• Enrollment (Actual): 310

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
  • Burgos, Spain
  • Ciudad Real, Spain
  • Madrid, Spain
  • Murcia, Spain
  • Santander, Spain
  • Sevilla, Spain
  • Valencia, Spain
  • Valladolid, Spain
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain
  • Aragon
    • Huesca, Aragon, Spain
  • Asturias
    • Gijon, Asturias, Spain
  • Ciudad Real
    • Alcazar de San Juan, Ciudad Real, Spain
  • Gerona
    • Girona, Gerona, Spain
  • Gran Canaria
    • Las Palmas, Gran Canaria, Spain
  • Madrid
    • Alcorcon, Madrid, Spain
    • Fuenlabrada, Madrid, Spain
    • Parla, Madrid, Spain
  • Navarra
    • Pamplona, Navarra, Spain
  • Pontevedra
    • Vigo, Pontevedra, Spain
  • Valencia
    • Castellon de la Plana, Valencia, Spain
    • Sagunto, Valencia, Spain
  • Vizcaya
    • Barakaldo, Vizcaya, Spain

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

Ulcerative colitis (UC) and Crohn's disease (CD) participants who started treatment with biologics between June 2011 and June 2013 will participate in the study.

Description

Inclusion Criteria:

• Adult participants (aged ≥18).
• Were diagnosed with UC or CD according to the "World Gastroenterology Organization Practice Guidelines for the Diagnosis and Management of inflammatory bowel disease (IBD) in 2010".
• Who were naive to biologics that started treatment with biologics between June 2011 and June 2013.
• Participants in whom biological treatment was prescribed according to clinical practice.
• Who gave written informed consent.

Exclusion Criteria:

• Were participating in a clinical trial during the study reference period.
• Participant that, according to investigator's criteria was not capable to understand and fill in the study questionnaires or to give written informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: Crohn's Disease; Participants with Crohn's disease who received biological treatment between June 2011 and June 2013.	Other: No Intervention
Cohort 2: Ulcerative Colitis; Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.	Other: No Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of the Comorbidities Profile in Inflammatory Bowel Disease (IBD) Participants on Lack of Treatment Response to Biological Therapy	Correlation between co-morbidities profile and lack of response, adjusted for sociodemographic and clinical profile of participants, logistic regression models were conducted. Lack of response was reduction of 2 points from baseline in Harvey-Bradshaw Indices (HBI) score for CD or Partial Mayo score (PMS) for UC after 10 weeks treatment with anti-tumour necrosis factor (TNF). HBI included general well-being (0=very well to 4=terrible), abdominal pain (0=none to 3=severe), number of liquid stools/day, abdominal mass (0=none to 3=tender), and complications (8 items; 1 score/item). The total score was sum of sub scores, where score <5=remission, 5-7=mild disease, 8-16=moderate disease and >16-severe disease. PMS included 3 sub-scores: stool frequency (0=normal to 3=>4 stools/day more than normal), rectal bleeding (0=none to 3=passing blood alone), and physician's global assessment (0=Normal to 3=severe). The total score was sum of sub scale scores from 0=normal to 9=severe disease.	Up to 10 weeks after start of treatment with biologics
Impact of the Comorbidities Profile in IBD Participants on Loss of Treatment Response to Biological Therapy	Correlation between co-morbidities profile and loss of response, adjusted for sociodemographic and clinical profile of participants, logistic regression models were conducted. Loss of response was defined as loss of drug effect along follow up with initial response i.e. reduction of 2 points from baseline in HBI score for CD or PMS for UC after 6 months of treatment with anti-TNF. HBI included general well-being (0=very well to 4=terrible), abdominal pain (0=none to 3=severe), number of liquid stools/day, abdominal mass (0=none to 3=tender), and complications (8 items; 1 score/item). The total score was sum of sub scores, <5=remission, 5-7=mild disease, 8-16=moderate disease and >16=severe disease. PMS score included 3 sub-scores: stool frequency (0=normal to 3=>4 stools/day more than normal), rectal bleeding (0=none to 3=passing blood alone), and physician's global assessment (0=Normal to 3=severe). The total score was sum of sub scale scores ranging from 0=normal to 9=severe disease.	Up to 6 months after start of treatment with biologics

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of the Extraintestinal Manifestations Profile in IBD Participants on Lack of Treatment Response to Biological Therapy	Correlation between extraintestinal manifestations profile and lack of response, adjusted for sociodemographic and clinical profile of participants, logistic regression models were conducted. Lack of response was reduction of at least 2 points from baseline in HBI score for CD or PMS for UC after 10 weeks treatment with TNF. HBI included general well-being (0=very well to 4=terrible), abdominal pain (0=none to 3=severe), number of liquid stools/day, abdominal mass (0=none to 3=tender), and complications (8 items; 1 score/item). The total score was sum of sub scores, where score <5=remission, 5-7=mild disease, 8-16=moderate disease and >16-severe disease. PMS included 3 sub-scores: stool frequency (0=normal to 3=>4 stools/day more than normal), rectal bleeding (0=none to 3=passing blood alone), and physician's global assessment (0=Normal to 3=severe). The total score was sum of sub scale scores from 0=normal to 9=severe disease.	Up to 10 weeks after start of treatment with biologics
Impact of the Extraintestinal Manifestations Profile in IBD Participants on Loss of Treatment Response to Biological Therapy	Correlation between extraintestinal manifestations profile and loss of response, adjusted for sociodemographic and clinical profile, logistic regression models were conducted. Loss of response was defined as loss of drug effect along follow up with initial response i.e. reduction of 2 points from baseline in HBI score for CD or PMS for UC after 6 months of treatment with anti-TNF. HBI included general well-being (0=very well to 4=terrible), abdominal pain (0=none to 3=severe), number of liquid stools/day, abdominal mass (0=none to 3=tender), and complications (8 items; 1 score/item). The total score was sum of sub scores, <5=remission, 5-7=mild disease, 8-16=moderate disease and >16=severe disease. PMS score included 3 sub-scores: stool frequency (0=normal to 3=>4 stools/day more than normal), rectal bleeding (0=none to 3=passing blood alone), and physician's global assessment (0=Normal to 3=severe). The total score was sum of sub scale scores ranging from 0=normal to 9=severe disease.	Up to 6 months after start of treatment with biologics
Percentage of IBD Participants With Comorbidities	Participants with CD and UC along with comorbidities were reported. Comorbidity referred to the presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition.	Day 1
Percentage of CD Participants With Comorbidities According to the Level of IBD Severity	Participants with CD were classified into IBD severe or non-severe at baseline based on the HBI scores according the following criteria:- HBI includes general well-being (0=very well to 4=terrible), abdominal pain (0=none to 3=severe), number of liquid stools per day, abdominal mass (0=none to 3=tender), and complications (8 items; 1 score/item). The total score is sum of sub scores, score <5=remission, 5-7=mild disease, 8-16=moderate disease and >16=severe disease.	Day 1
Percentage of UC Participants With Comorbidities According to the Level of IBD Severity	Participants with UC were classified into IBD severe or non-severe at baseline based on the PMS scores according the following criteria:- PMS score includes 3 sub-scores: stool frequency (0=normal to 3=>4 stools/day more than normal), rectal bleeding (0=none to 3=passing blood alone), and physician's global assessment (0=Normal to 3=severe). The total score is sum of sub scale scores ranging from 0=normal to 9=severe disease.	Day 1

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Marin-Jimenez I, Bastida G, Fores A, Garcia-Planella E, Arguelles-Arias F, Sarasa P, Tagarro I, Fernandez-Nistal A, Montoto C, Aguas M, Santos-Fernandez J, Bosca-Watts MM, Ferreiro R, Merino O, Aldeguer X, Cortes X, Sicilia B, Mesonero F, Barreiro-de Acosta M. Impact of comorbidities on anti-TNFalpha response and relapse in patients with inflammatory bowel disease: the VERNE study. BMJ Open Gastroenterol. 2020 Mar 26;7(1):e000351. doi: 10.1136/bmjgast-2019-000351. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2016
• Primary Completion (Actual): April 4, 2018
• Study Completion (Actual): April 4, 2018

Study Registration Dates

• First Submitted: August 5, 2016
• First Submitted That Met QC Criteria: August 5, 2016
• First Posted (Estimate): August 10, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: July 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: Vedolizumab-5016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.