Trial Outcomes & Findings for A Retrospective Observational Study to Assess the Impact of Co-morbidities on Treatment Response in Inflammatory Bowel Disease (NCT NCT02861118)

Last Updated: 2019-08-14

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

310 participants

Primary outcome timeframe

Up to 10 weeks after start of treatment with biologics

Results posted on

2019-08-14

Participant Flow

Participants took part in the study at the 25 investigative sites in Spain from 26 October 2016 to 04 April 2018.

Participants with a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) who started treatment with biologics between June 2011 and June 2013, participated in the study. Total 357 participants were registered, out of which only 310 participants were analyzed.

Participant milestones

Participant milestones
Measure	Cohort 1: Crohn's Disease Participants with Crohn's disease who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Overall Study STARTED	194	116
Overall Study COMPLETED	194	116
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Number analyzed is the number of participants with evaluable data at this baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Crohn's Disease n=194 Participants Participants with Crohn's disease who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis n=116 Participants Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.	Total n=310 Participants Total of all reporting groups
Age, Continuous	43.8 years STANDARD_DEVIATION 12.8 • n=5 Participants	46.8 years STANDARD_DEVIATION 13.3 • n=7 Participants	44.9 years STANDARD_DEVIATION 13.00 • n=5 Participants
Sex/Gender, Customized Male	103 Participants n=5 Participants	63 Participants n=7 Participants	166 Participants n=5 Participants
Sex/Gender, Customized Female	90 Participants n=5 Participants	47 Participants n=7 Participants	137 Participants n=5 Participants
Sex/Gender, Customized Not Available	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	189 Participants n=5 Participants	108 Participants n=7 Participants	297 Participants n=5 Participants
Race/Ethnicity, Customized Latin	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Gipsy	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Arab	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Available	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Spain	194 Participants n=5 Participants	116 Participants n=7 Participants	310 Participants n=5 Participants
Working Status Employed by Other	115 Participants n=5 Participants	51 Participants n=7 Participants	166 Participants n=5 Participants
Working Status Self Employed	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Working Status Retired	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Working Status Housework	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Working Status Unemployed	17 Participants n=5 Participants	4 Participants n=7 Participants	21 Participants n=5 Participants
Working Status Student	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Working Status Permanently Unable to Work	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Working Status Temporarily Unable to Work	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Working Status Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Working Status Not Available	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Level of Education Secondary Education	101 Participants n=5 Participants	46 Participants n=7 Participants	147 Participants n=5 Participants
Level of Education Primary Education	45 Participants n=5 Participants	30 Participants n=7 Participants	75 Participants n=5 Participants
Level of Education University Education	42 Participants n=5 Participants	32 Participants n=7 Participants	74 Participants n=5 Participants
Level of Education Uneducated	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Level of Education Not Available	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Smoking Habits Non-smoker	86 Participants n=5 Participants	70 Participants n=7 Participants	156 Participants n=5 Participants
Smoking Habits Ex-smoker	52 Participants n=5 Participants	37 Participants n=7 Participants	89 Participants n=5 Participants
Smoking Habits Smoker	55 Participants n=5 Participants	7 Participants n=7 Participants	62 Participants n=5 Participants
Smoking Habits Not Available	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Alcohol Abuse Yes	4 Participants n=5 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.	0 Participants n=7 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.	4 Participants n=5 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.
Alcohol Abuse No	189 Participants n=5 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.	114 Participants n=7 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.	303 Participants n=5 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.
Alcohol Abuse Not Available	1 Participants n=5 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.	2 Participants n=7 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.	3 Participants n=5 Participants • Number analyzed is the number of participants with evaluable data at this baseline measure.

PRIMARY outcome

Timeframe: Up to 10 weeks after start of treatment with biologics

Population: Analyzed participants included all participants who didn't had screen failure, met all the inclusion criteria and had enough information about response to the biological treatment.

Outcome measures

Outcome measures
Measure	Participants With Inflammatory Bowel Disease (IBD) n=310 Participants Participants with IBD (Crohn's disease and ulcerative colitis) who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Impact of the Comorbidities Profile in Inflammatory Bowel Disease (IBD) Participants on Lack of Treatment Response to Biological Therapy IBD	0.59 odds ratio Interval 0.37 to 0.93	—
Impact of the Comorbidities Profile in Inflammatory Bowel Disease (IBD) Participants on Lack of Treatment Response to Biological Therapy Corticosteroids	2.16 odds ratio Interval 1.25 to 3.73	—
Impact of the Comorbidities Profile in Inflammatory Bowel Disease (IBD) Participants on Lack of Treatment Response to Biological Therapy Chronic Obstructive Pulmonary Disease	2.67 odds ratio Interval 1.33 to 5.35	—

PRIMARY outcome

Timeframe: Up to 6 months after start of treatment with biologics

Population: Analyzed participants included all participants who didn't had screen failure, met all the inclusion criteria and had enough information about response to the biological treatment.

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.

Outcome measures

Outcome measures
Measure	Participants With Inflammatory Bowel Disease (IBD) n=310 Participants Participants with IBD (Crohn's disease and ulcerative colitis) who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Impact of the Comorbidities Profile in IBD Participants on Loss of Treatment Response to Biological Therapy IBD	0.58 odds ratio Interval 0.34 to 0.99	—
Impact of the Comorbidities Profile in IBD Participants on Loss of Treatment Response to Biological Therapy Corticosteroids	2.45 odds ratio Interval 1.35 to 4.44	—
Impact of the Comorbidities Profile in IBD Participants on Loss of Treatment Response to Biological Therapy Myocardial Infarction	3.30 odds ratio Interval 1.48 to 7.35	—

SECONDARY outcome

Timeframe: Up to 10 weeks after start of treatment with biologics

Population: Analyzed participants included all participants who didn't had screen failure, met all the inclusion criteria and had enough information about response to the biological treatment.

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.

Outcome measures

Outcome measures
Measure	Participants With Inflammatory Bowel Disease (IBD) n=310 Participants Participants with IBD (Crohn's disease and ulcerative colitis) who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Impact of the Extraintestinal Manifestations Profile in IBD Participants on Lack of Treatment Response to Biological Therapy	2.08 odds ratio Interval 1.22 to 3.54	—

SECONDARY outcome

Timeframe: Up to 6 months after start of treatment with biologics

Population: Analyzed participants included all participants who didn't had screen failure, met all the inclusion criteria and had enough information about response to the biological treatment.

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.

Outcome measures

Outcome measures
Measure	Participants With Inflammatory Bowel Disease (IBD) n=310 Participants Participants with IBD (Crohn's disease and ulcerative colitis) who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Impact of the Extraintestinal Manifestations Profile in IBD Participants on Loss of Treatment Response to Biological Therapy Corticosteroids	2.57 odds ratio Interval 1.43 to 4.61	—
Impact of the Extraintestinal Manifestations Profile in IBD Participants on Loss of Treatment Response to Biological Therapy Skin Disease	2.73 odds ratio Interval 1.42 to 5.25	—

SECONDARY outcome

Timeframe: Day 1

Population: Analyzed participants included all participants who didn't had screen failure, met all the inclusion criteria and had enough information about response to the biological treatment. Number analyzed is the number of participants with evaluable data at the given time-point.

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.

Outcome measures

Outcome measures
Measure	Participants With Inflammatory Bowel Disease (IBD) n=194 Participants Participants with IBD (Crohn's disease and ulcerative colitis) who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis n=116 Participants Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Percentage of IBD Participants With Comorbidities Myocardial Infarction	2.2 percentage of participants	0.9 percentage of participants
Percentage of IBD Participants With Comorbidities Congestive Heart Failure	1.6 percentage of participants	0.9 percentage of participants
Percentage of IBD Participants With Comorbidities Peripheral Vascular Disease	1.6 percentage of participants	0.0 percentage of participants
Percentage of IBD Participants With Comorbidities Cardiovascular Disease	0.5 percentage of participants	2.6 percentage of participants
Percentage of IBD Participants With Comorbidities Chronic Obstructive Pulmonary Disease	3.2 percentage of participants	4.4 percentage of participants
Percentage of IBD Participants With Comorbidities Connective Tissue Disease	2.7 percentage of participants	3.5 percentage of participants
Percentage of IBD Participants With Comorbidities Peptic Ulcer Disease	0.5 percentage of participants	0.9 percentage of participants
Percentage of IBD Participants With Comorbidities Mild Chronic Hepatopathy	1.1 percentage of participants	3.5 percentage of participants
Percentage of IBD Participants With Comorbidities Diabetes Mellitus	0.5 percentage of participants	5.3 percentage of participants
Percentage of IBD Participants With Comorbidities Diabetes with Lesions in Target Organs	0.0 percentage of participants	0.9 percentage of participants
Percentage of IBD Participants With Comorbidities Solid Tumor	2.2 percentage of participants	0.9 percentage of participants
Percentage of IBD Participants With Comorbidities Leukemia	0.0 percentage of participants	0.9 percentage of participants
Percentage of IBD Participants With Comorbidities Lymphoma	0.5 percentage of participants	0.0 percentage of participants
Percentage of IBD Participants With Comorbidities Moderate-Severe Chronic Hepatopathy	0.5 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Day 1

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.

Outcome measures

Outcome measures
Measure	Participants With Inflammatory Bowel Disease (IBD) n=194 Participants Participants with IBD (Crohn's disease and ulcerative colitis) who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Percentage of CD Participants With Comorbidities According to the Level of IBD Severity Non-Severe Disease	62.4 percentage of participants	—
Percentage of CD Participants With Comorbidities According to the Level of IBD Severity Severe Disease	8.3 percentage of participants	—

SECONDARY outcome

Timeframe: Day 1

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.

Outcome measures

Outcome measures
Measure	Participants With Inflammatory Bowel Disease (IBD) n=116 Participants Participants with IBD (Crohn's disease and ulcerative colitis) who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Percentage of UC Participants With Comorbidities According to the Level of IBD Severity Severe Disease	91.7 percentage of participants	—
Percentage of UC Participants With Comorbidities According to the Level of IBD Severity Non-Severe Disease	37.6 percentage of participants	—

Adverse Events

Cohort 1: Crohn's Disease

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort 2: Ulcerative Colitis

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Crohn's Disease n=194 participants at risk Participants with Crohn's disease who received biological treatment between June 2011 and June 2013.	Cohort 2: Ulcerative Colitis n=116 participants at risk Participants with ulcerative colitis who received biological treatment between June 2011 and June 2013.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/194 • Time since participants started biological treatment until study visit (Day 1) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.86% 1/116 • Time since participants started biological treatment until study visit (Day 1) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Adverse event data not reported

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER