Crohn's Disease
Conditions
Keywords
Crohn's Disease
Brief summary
This multicenter, prospective, post marketing observational study (PMOS) was designed to demonstrate long-term effects of anti-Tumor Necrosis Factor therapies on Work Productivity and Impairment scales in participants with moderate to severe Crohn's Disease (CD) under routine conditions. Secondary objectives of this study were long-term improvement of Quality of Life (QoL), evaluation of improvement of extraintestinal symptoms and comorbidities, and evaluation of safety.
Detailed description
Male or female participants between 18 - 65 years of age with moderate to severe CD for whom the treating physician had recently initiated an anti-TNF treatment were included in this study. Anti-TNF treatments were administered according to the treating physician's decision and applicable product label in Turkey. No interventions were made to the treatment and the participant discontinuance or to the follow-up decisions of the treating physician. Enrolled participants were observed for one year.
Interventions
None listed
Sponsors
AbbVie
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants between 18-65 years of age with moderately to severely (Crohn's Disease Activity Index 220-450) active Crohn's Disease with or without fistula formation * Participants who were able to provide authorization to use and disclose information related to the study * Proven diagnosis of Crohn's Disease in accordance with international diagnostic criteria such as European Crohn's and Colitis Organization (ECCO) guidelines * Participants for whom the physician had initiated anti-Tumor Necrosis Factor treatment in accordance with Turkish Ministry of Health regulations and reimbursements
Exclusion criteria
* Participants who had a history of any kind of biological therapy and/or anti-Tumor Necrosis Factor treatments for Crohn's Disease or other indications * Participants who had septic complications (active infection and/or active tuberculosis (TB), undrained abscess) * Participants who had bowel obstructions and fibrotic strictures * Participants who had received any investigational drug within 30 days prior to the Visit 1 at baseline * For any reason, participants who were considered by the investigator to be unsuitable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Activity Impairment (TAI) | At baseline and 12 months | The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was used to assess impairments in both paid work and unpaid work due to symptoms of Crohn's Disease. The self-administered questionnaire consisted of 6 questions. Question 6 asked participants to indicate the degree to which their health affected their regular activities in the past 7 days. Total activity impairment is the percent impairment of non-work related activities due to health problems and was calculated with the formula (Q6/10) × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. |
| Work Productivity and Activity Index (WPAI): Absenteeism | At baseline and 12 months | The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was used to assess impairments in both paid work and unpaid work due to symptoms of Crohn's Disease. The self-administered questionnaire consisted of 6 questions. Question 2 asked participants to indicate the number of hours missed due to health problems in the past 7 days. Question 4 asked participants to indicate the number of hours that they worked in the past 7 days. Absenteeism (work time missed) was defined as the percentage of time absent from work due to health problems in the past week and was calculated by the formula Q2/(Q2 + Q4) × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. |
| Work Productivity and Activity Index (WPAI): Presenteeism | At baseline and 12 months | The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was used to assess impairments in both paid work and unpaid work due to symptoms of Crohn's Disease. The self-administered questionnaire consisted of 6 questions. Question 5 asked participants the degree to which their health affected productivity while working in the past 7 days, on a scale ranging from 0 to 10, with 0 indicating that health problems had no effect on their work and 10 indicating that health problems completely prevented the participant from working. Presenteeism (impairment at work) was calculated by the formula (Q5/10) × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. |
| Total Work Productivity Impairment (TWPI) | At baseline and 12 months | The Work Productivity and Activity Impairment: General Health (WPAI:GH) self-administered questionnaire was used to assess impairments in work due to symptoms of Crohn's Disease. Q2 asked participants the number of hours missed due to health problems in the past 7 days. Q4 asked participants the number of hours that they worked in the past 7 days. Q5 asked participants the degree to which their health affected productivity while working in the past 7 days, on a scale ranging from 0 (health problems had no effect) to 10 (health problems completely prevented them from working). Total work productivity impairment (TWPI) is the combined absenteeism and presenteeism for employed participants, the percentage of overall work productivity lost due to health problems. TWPI was calculated using the formula Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4)))×(Q5/10)\] × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Short Form 36 (SF-36) Health Survey Scores | At baseline and 12 months | The Short Form 36 (SF-36) Health Survey was used to determine participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item were summed and averaged (range = 0 worst to 100 best). Increases from baseline indicate improvement. |
| Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | At baseline and 12 months | The Inflammatory Bowel Disease Questionnaire (IBDQ) is a 32-item self-administered questionnaire to measure health-related quality of life in adults with Crohn's Disease. The 32 items are grouped into subscales: bowel-related symptoms (10 items), systemic symptoms (5 items), social function (5 items), and emotional function (12 items). Responses to each item within each subscale range from 1 (significant impairment) to 7 (no impairment), and mean scores ranging from 1 to 7 are calculated for each subscale. Higher scores indicate a better quality of life. |
| Change in Extra-intestinal Symptoms | At baseline and 12 months | Extra-intestinal manifestations of Crohn's Disease (skeletal system \[bones and muscle\], dermatological \[skin\], hepatobiliary system \[liver, gall bladder, and bile ducts\], ocular \[eyes\] and oral \[mouth\]) were documented by the study investigators at each visit. |
| Number of Participants With Serious Adverse Events | From the time of informed consent until 30 days or 5 half-lives following the last dose, up to 62 weeks | A serious adverse event was defined as any untoward medical occurrence in a clinical investigation participant that met at least 1 of the following criteria: death, life-threatening, hospitalization or prolongation of hospitalization, congenital anomaly, persistent or significant disability/incapacity, important medical event requiring medical or surgical intervention to prevent serious outcome, elective or spontaneous abortion. |
Participant flow
Pre-assignment details
A total of 106 participants were enrolled in the study and were intended to be followed for 12 months.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Moderate to Severe Crohn's Disease Participants for whom the treating physician had recently initiated an anti-Tumor Necrosis Factor (TNF) treatment | 106 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 33 |
Baseline characteristics
| Characteristic | Participants With Moderate to Severe Crohn's Disease |
|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 10.9 |
| Anti-TNF Treatments Adalimumab | 78 Participants |
| Anti-TNF Treatments Infliximab | 23 Participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 2 / 106 |
Outcome results
Primary
Total Activity Impairment (TAI)
The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was used to assess impairments in both paid work and unpaid work due to symptoms of Crohn's Disease. The self-administered questionnaire consisted of 6 questions. Question 6 asked participants to indicate the degree to which their health affected their regular activities in the past 7 days. Total activity impairment is the percent impairment of non-work related activities due to health problems and was calculated with the formula (Q6/10) × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time frame: At baseline and 12 months
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Total Activity Impairment (TAI) | Baseline | 47.0 units on a scale | Standard Deviation 32 |
| Participants With Moderate to Severe Crohn's Disease | Total Activity Impairment (TAI) | 12 months | 30.0 units on a scale | Standard Deviation 27 |
Comparison: The null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Primary
Total Work Productivity Impairment (TWPI)
The Work Productivity and Activity Impairment: General Health (WPAI:GH) self-administered questionnaire was used to assess impairments in work due to symptoms of Crohn's Disease. Q2 asked participants the number of hours missed due to health problems in the past 7 days. Q4 asked participants the number of hours that they worked in the past 7 days. Q5 asked participants the degree to which their health affected productivity while working in the past 7 days, on a scale ranging from 0 (health problems had no effect) to 10 (health problems completely prevented them from working). Total work productivity impairment (TWPI) is the combined absenteeism and presenteeism for employed participants, the percentage of overall work productivity lost due to health problems. TWPI was calculated using the formula Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4)))×(Q5/10)\] × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time frame: At baseline and 12 months
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Total Work Productivity Impairment (TWPI) | Baseline | 24.2 units on a scale | Standard Deviation 21.2 |
| Participants With Moderate to Severe Crohn's Disease | Total Work Productivity Impairment (TWPI) | 12 months | 15.7 units on a scale | Standard Deviation 16.4 |
Comparison: The null hypothesis was set as no difference.p-value: =0.006Wilcoxon signed-ranked test
Primary
Work Productivity and Activity Index (WPAI): Absenteeism
The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was used to assess impairments in both paid work and unpaid work due to symptoms of Crohn's Disease. The self-administered questionnaire consisted of 6 questions. Question 2 asked participants to indicate the number of hours missed due to health problems in the past 7 days. Question 4 asked participants to indicate the number of hours that they worked in the past 7 days. Absenteeism (work time missed) was defined as the percentage of time absent from work due to health problems in the past week and was calculated by the formula Q2/(Q2 + Q4) × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time frame: At baseline and 12 months
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Work Productivity and Activity Index (WPAI): Absenteeism | Baseline | 38.3 units on a scale | Standard Deviation 39 |
| Participants With Moderate to Severe Crohn's Disease | Work Productivity and Activity Index (WPAI): Absenteeism | 12 months | 14.2 units on a scale | Standard Deviation 27 |
Comparison: The null hypothesis was set as no difference.p-value: =0.004Wilcoxon signed-ranked test
Primary
Work Productivity and Activity Index (WPAI): Presenteeism
The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was used to assess impairments in both paid work and unpaid work due to symptoms of Crohn's Disease. The self-administered questionnaire consisted of 6 questions. Question 5 asked participants the degree to which their health affected productivity while working in the past 7 days, on a scale ranging from 0 to 10, with 0 indicating that health problems had no effect on their work and 10 indicating that health problems completely prevented the participant from working. Presenteeism (impairment at work) was calculated by the formula (Q5/10) × 100%. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time frame: At baseline and 12 months
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Work Productivity and Activity Index (WPAI): Presenteeism | Baseline | 39.8 units on a scale | Standard Deviation 31.7 |
| Participants With Moderate to Severe Crohn's Disease | Work Productivity and Activity Index (WPAI): Presenteeism | 12 months | 21.8 units on a scale | Standard Deviation 19.3 |
Comparison: The null hypothesis was set as no difference.p-value: =0.022Wilcoxon signed-ranked test
Secondary
Change in Extra-intestinal Symptoms
Extra-intestinal manifestations of Crohn's Disease (skeletal system \[bones and muscle\], dermatological \[skin\], hepatobiliary system \[liver, gall bladder, and bile ducts\], ocular \[eyes\] and oral \[mouth\]) were documented by the study investigators at each visit.
Time frame: At baseline and 12 months
Population: Participants with available data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Skeletal symptoms present (Baseline) | 20 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Skeletal symptoms present (12 months) | 8 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Dermatological symptoms present (Baseline) | 7 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Dermatological symptoms present (12 months) | 3 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Hepatobiliary symptoms present (Baseline) | 0 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Hepatobiliary symptoms present (12 months) | 0 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Ocular symptoms present (Baseline) | 1 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Ocular symptoms present (12 months) | 0 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Oral symptoms present (Baseline) | 4 Participants |
| Participants With Moderate to Severe Crohn's Disease | Change in Extra-intestinal Symptoms | Oral symptoms present (12 months) | 0 Participants |
Secondary
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a 32-item self-administered questionnaire to measure health-related quality of life in adults with Crohn's Disease. The 32 items are grouped into subscales: bowel-related symptoms (10 items), systemic symptoms (5 items), social function (5 items), and emotional function (12 items). Responses to each item within each subscale range from 1 (significant impairment) to 7 (no impairment), and mean scores ranging from 1 to 7 are calculated for each subscale. Higher scores indicate a better quality of life.
Time frame: At baseline and 12 months
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Bowel-related Symptoms Score (Baseline) | 4.5 units on a scale | Standard Deviation 1.1 |
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Bowel-related Symptoms Score (12 months) | 5.2 units on a scale | Standard Deviation 1.1 |
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Systemic Symptoms Score (Baseline) | 3.8 units on a scale | Standard Deviation 1.4 |
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Systemic Symptoms Score (12 months) | 4.9 units on a scale | Standard Deviation 1.1 |
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Emotional Function Score (Baseline) | 4.0 units on a scale | Standard Deviation 1.1 |
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Emotional Function Score (12 months) | 4.7 units on a scale | Standard Deviation 1 |
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Social Function Score (Baseline) | 4.3 units on a scale | Standard Deviation 1.5 |
| Participants With Moderate to Severe Crohn's Disease | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Scores | Social Function Score (12 months) | 5.3 units on a scale | Standard Deviation 1.5 |
Comparison: Bowel-related Symptoms Scores: The null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Comparison: Systemic Symptoms Scores:The null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Comparison: Emotional Function Scores: the null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Comparison: Social Function Scores: The null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Secondary
Change in Short Form 36 (SF-36) Health Survey Scores
The Short Form 36 (SF-36) Health Survey was used to determine participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item were summed and averaged (range = 0 worst to 100 best). Increases from baseline indicate improvement.
Time frame: At baseline and 12 months
Population: Participants with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Physical Functioning Score (Baseline) | 62.8 units on a scale | Standard Deviation 30.1 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Physical Functioning Score (12 months) | 81.2 units on a scale | Standard Deviation 21.4 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Role-Physical Score (Baseline) | 29.3 units on a scale | Standard Deviation 39.1 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Role-Physical Score (12 months) | 67.2 units on a scale | Standard Deviation 41.5 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Role-Emotional Score (Baseline) | 35.2 units on a scale | Standard Deviation 39.2 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Role-Emotional Score (12 months) | 62.8 units on a scale | Standard Deviation 43.9 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Vitality Score (Baseline) | 46.9 units on a scale | Standard Deviation 26.9 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Vitality Score (12 months) | 58.6 units on a scale | Standard Deviation 20.8 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Mental Health Score (Baseline) | 53.6 units on a scale | Standard Deviation 23.6 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Mental Health Score (12 months) | 63.0 units on a scale | Standard Deviation 16.6 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Social Functioning Score (Baseline) | 58.6 units on a scale | Standard Deviation 27.4 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Social Functioning Score (12 months) | 70.3 units on a scale | Standard Deviation 22.6 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Bodily Pain Score (Baseline) | 51.9 units on a scale | Standard Deviation 30 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | Bodily Pain Score (12 months) | 73.0 units on a scale | Standard Deviation 23.7 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | General Health Score (Baseline) | 44.8 units on a scale | Standard Deviation 22.2 |
| Participants With Moderate to Severe Crohn's Disease | Change in Short Form 36 (SF-36) Health Survey Scores | General Health Score (12 months) | 54.9 units on a scale | Standard Deviation 19.7 |
Comparison: Physical Functioning Scores: the null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Comparison: Role-Physical Scores: the null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Comparison: Role-Emotional Scores: the null hypothesis was set as no difference.p-value: =0.001Wilcoxon signed-ranked test
Comparison: Vitality Scores: the null hypothesis was set as no difference.p-value: =0.019Wilcoxon signed-ranked test
Comparison: Mental Health Scores: the null hypothesis was set as no difference.p-value: =0.017Wilcoxon signed-ranked test
Comparison: Social Functioning Scores: the null hypothesis was set as no difference.p-value: =0.007Wilcoxon signed-ranked test
Comparison: Bodily Pain Scores: the null hypothesis was set as no difference.p-value: <0.001Wilcoxon signed-ranked test
Comparison: General Health Scores: the null hypothesis was set as no difference.p-value: =0.005Wilcoxon signed-ranked test
Secondary
Number of Participants With Serious Adverse Events
A serious adverse event was defined as any untoward medical occurrence in a clinical investigation participant that met at least 1 of the following criteria: death, life-threatening, hospitalization or prolongation of hospitalization, congenital anomaly, persistent or significant disability/incapacity, important medical event requiring medical or surgical intervention to prevent serious outcome, elective or spontaneous abortion.
Time frame: From the time of informed consent until 30 days or 5 half-lives following the last dose, up to 62 weeks
Population: All enrolled participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Moderate to Severe Crohn's Disease | Number of Participants With Serious Adverse Events | 2 Participants |