Non-interventional Study of Moderate to Severe Inflammatory Bowel Disease in Brazil

Study Overview
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Brief Summary
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The purpose of this study is to gather information regarding the population with moderate to severe inflammatory bowel disease (IBD), the burden of the disease, and understand their treatment patterns, particularly on the use of available biologic therapies.

Detailed Description
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This is a non-interventional study to determine the rate of control of disease activity in moderate to severe inflammatory bowel disease (IBD) participants, with two parts: cross-sectional evaluation (Day 1) with retrospective data collection and a prospective 12-month evaluation for patients with active IBD at cross-sectional evaluation (Day 1). The study enrolled 407 patients. This multicenter trial was conducted in Brazil. Retrospective data of previous IBD treatments (drug, dose, treatment duration, drug changes), and use of other health resources related with the management of IBD for previous three years will be collected. Prospective data was collected for a period of 12 months in participants with active disease. UC participants, with no or light disease activity at Day 1 did not continue to 12-month follow up. CD participants, with no or light disease activity at Day 1 but with colonoscopy or calprotectin levels (i.e, calprotectin >200 ug/g) in the previous year suggestive of inadequate control of activity progressed to 12-month follow up.

Official Title
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Real-world Data of Moderate to Severe Inflammatory Bowel Disease in Brazil: a Non-interventional, Multicenter Study to Evaluate Disease Control, Treatment Patterns, Burden of Disease and Quality of Life (RISE BR)

Conditions
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Inflammatory Bowel Disease

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female. 18 years or older (at the time of diagnosis of moderate to severe UC or CD). Diagnosis of moderate to severe CD or UC for at least 6 months prior to Day 1 appointment according the clinical or endoscopic \ criteria. Has provided the written informed consent. For the prospective period, eligible participants should present at least one of the following criteria that will only be applied at Day 1: For CD participants: Harvey Bradshaw Index (HBI) ≥8 or Crohn's Disease Activity Index (CDAI) ≥220 or Considering that for CD participants, the disease activity may not be clearly documented only with clinical data, some objective criteria may be considered as entry criteria for the 12-month prospective period: Colonoscopy in the previous year suggestive of inadequate control of activity or, Calprotectin levels in the previous year suggestive of inadequate control of activity (i.e, calprotectin >200 µg/g). For UC: partial Mayo Score ≥5. Note: Participants with colostomy and prospective period: Although clinical scales defined above are impacted by colostomy these participants will not be excluded from the protocol to ensure the assessment of different clinical presentations of the IBD. In addition, participants with colostomy must follow the same criteria as above to be eligible to the prospective phase. Exclusion Criteria: Indeterminate or not classified colitis. Current or previous participation in interventional clinical trial (within the last 3 years). In addition, for the 12-month prospective period, participants will be excluded if: Presenting mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation. Hospitalized participants at Day 1. Current off label treatment with Vedolizumab. Study Discontinuation Criteria It will be considered a premature termination the situation in which the participant discontinues the participation, i.e. they are withdrawn from the study before completing the 12 months of follow up period (365 days ± 14 days from Day 1), due to any of the reasons listed below: Withdrawal of consent: participants who for any reason withdraw the free and informed consent; Lost to follow-up (no return of the participant on the expected date of visit - drop-out from the protocol); Death; Study termination; Any situation that places the participant within one of the exclusion criteria. Note: Participants who are eligible for the prospective period, it means, with active disease at Day 1 but who during the 12 months period presents disease remission and/or no activity disease condition, are allowed to continue the participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Crohn's Disease<br>Participants with diagnosis of moderate to severe Crohn's disease (CD) for at least 6 months prior to Day 1 were observed to collect the retrospective data including previous inflammatory bowel disease (IBD) treatments (drug dose, treatment duration, drug changes), and use of other health resources related with the management of IBD for previous three years at Day 1. Participants with active IBD and CD at Day 1 were followed up for 12 months in prospective phase. | Other: No Intervention<br> <br> |
| Ulcerative Colitis<br>Participants diagnosed with diagnosis of moderate to severe ulcerative colitis (UC) for at least 6 months prior to Day 1 were observed to collect the retrospective data including previous inflammatory bowel disease (IBD) treatments (drug dose, treatment duration, drug changes), and use of other health resources related with the management of IBD for previous three years at Day 1. Participants with active IBD and UC at Day 1 were followed up for 12 months in prospective phase. | Other: No Intervention<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Active Crohn's Disease (CD) at Day 1 | Participants with Harvey Bradshaw Index (HBI) score of ≥8 or Crohn´s Disease Activity Index (CDAI) ≥220 points at Day 1 were classified as participants with active disease. HBI scale assessed five dimensions (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications). These dimensions were scored from the previous day. The total score ranges from 0 to 25. The CDAI evaluated the severity of signs and symptoms of CD. Collected data included information on the number of liquid stools, intensity of abdominal pain, general well-being, presence of comorbid conditions, use of medications for diarrhea, physical examination, and laboratory findings (abdominal mass, hematocrit, body weight), yielding 8 items that were combined with data from a 7-day diary to obtain the total CDAI score which ranges from 0 to approximately 600 points, where higher score indicates higher disease activity. | Day 1 | 
| Number of Participants With Active Ulcerative Colitis (UC) at Day 1 | Participants with ≥5 points in Partial Mayo Score were classified as active UC disease. The mayo score without endoscopy measured severity of ulcerative colitis. Three sub-scores for stool frequency, rectal bleeding, and physician's global assessment were each graded from 0 to 3 with higher scores indicating more severe disease. Individual sub-scores were then summed to provide the total score ranging from 0 (normal or inactive disease) to 9 (severe disease). | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Moderate to Severe CD or UC Stratified by Age, Gender, Professional Status, Family History, Educational Level and Income at Day 1 |  | Day 1 | 
| Number of Participants With Moderate to Severe CD or UC Stratified by Clinical Variables | Clinical variables included IBD type:CD/UC; anthropometric (Height, Weight and BMI); Family history; Smoking habits; Medical History/Comorbidities; Disease location -L1=ileal, L2=colonic disease, L3=ileocolic, L4=isolated upper GI tract disease location. Behavior as B1/B1+P=Non stenosing/non penetrating or B1+P=Non stenosing/non penetrating+perianal disease, B2/B2+P=Stenosing/B2+P=Stenosing+perianal disease B3/B3+P=Penetrating, B3+P=Penetrating+perianal disease, P=Penetrating disease. Extension of inflammation as E1=distal UC: proctitis or E1=distal UC: proctosigmoiditis extension of inflammation E2/E3=left-sided: mucosa inflammation extending up to splenic flexure or E3=pancolitis: mucosa inflammation up to proximal transverse colon and beyond extension of inflammation and severity of UC as S0=Clinical remission, S1=Mild UC, S2=Moderate UC, S3=Severe UC. Steroid behavior; Colonoscopy, Calprotectin levels >200ug/g, Eligibility for 12-month follow-up. | Day 1 | 
| Percentage of Participants With Moderate to Severe CD or UC Who Used Various Types of Therapies for IBD in Previous 3 Years | Therapies for IBD included aminosalicylates, steroids, immunossupressors, biologics, antibiotics, surgeries and others. One participant could use more than one therapy. | Within the previous 3 years including Day 1 | 
| Percentage of Participants With Moderate to Severe CD or UC Treated With Biologic Therapy Within 3 Previous Years | IBD types included CD and UC. Biologic therapies included treatment with infliximab, adalimumab, vedolizumab, certolizumab, golimumab and ustekimumab. One participant could use more than one biologic therapy. | Within the previous 3 years including Day 1 | 
| Percentage of Participants With Moderate to Severe CD or UC Who Have Not Responded Previously to Biologic Therapies | IBD types included CD and UC. Biologic therapies included treatment with infliximab, adalimumab, vedolizumab, certolizumab, golimumab and ustekimumab. | Day 1 | 
| Percentage of Participants With Moderate to Severe CD or UC Who Were Ongoing IBD Treatment at Day 1 | Participants with moderate to severe CD or UC ongoing IBD treatment at Day 1 were reported. | Day 1 | 
| Number of Participants With Moderate to Severe Activity of CD or With Light or no Activity Stratified by Socio-demographic Variables | Socio-demographic variables included gender and professional status. | Day 1 | 
| Number of Participants With Moderate to Severe Activity of CD or With Light or no Activity Stratified by Clinical Variables | Clinical variables included IBD type:CD/UC; Family history; Smoking habits; Medical History/Comorbidities; Disease location -L1=ileal, L2=colonic disease, L3=ileocolic, L4=isolated upper GI tract disease location. Behavior as B1/B1+P=Non stenosing/non penetrating or B1+P=Non stenosing/non penetrating+perianal disease, B2/B2+P=Stenosing/B2+P=Stenosing+perianal disease B3/B3+P=Penetrating, B3+P=Penetrating+perianal disease, P=Penetrating disease. Steroid behavior; Colonoscopy, Calprotectin levels >200ug/g. | Day 1 | 
| Percentage of Participants With Treatment Beginning or Ongoing at Day 1 by Moderate to Severe Activity of CD or With Light or no Activity Stratified by Treatment Variables | Treatment variables included previous treatments or regimens (aminosalicylates, steroids, immunossupressors, biologics, antibiotics); and previous surgeries for IBD. One participant could use more than one treatment regimens. | Day 1 | 
| Number of Participants With Moderate to Severe Activity of UC or With Light or no Activity Stratified by Socio-demographic Variables | Socio-demographic variables included gender and professional status. | Day 1 | 
| Number of Participants With Moderate to Severe Activity of UC or With Light or no Activity Stratified by Clinical Variables | Clinical variables included IBD type:CD/UC; Family history; Smoking habits; Medical History/Comorbidities; Extension of inflammation as E1=distal UC: proctitis or E1=distal UC: proctosigmoiditis extension of inflammation E2/E3=left-sided: mucosa inflammation extending up to splenic flexure or E3=pancolitis: mucosa inflammation up to proximal transverse colon and beyond extension of inflammation and severity of UC as S0=Clinical remission, S1=Mild UC, S2=Moderate UC, S3=Severe UC. Steroid behavior; Colonoscopy, Calprotectin levels >200ug/g. | Day 1 | 
| Percentage of Participants With Treatment Beginning or Ongoing at Day 1 by Moderate to Severe Activity of UC or With Light or no Activity Stratified by Treatment Variables | Treatment variables include previous treatments or regimens (aminosalicylates, steroids, immunomodulators, immunossupressors, biologics, antibiotics); and previous surgeries for IBD. One participant could use more than one treatment regimens. | Day 1 | 
| Harvey Bradshaw Index (HBI) Total Score in Participants Who Had Moderate to Severe Active CD at Day 1 and Month 12 | HBI scale assessed the severity of CD. HBI scale assessed five dimensions (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications). These dimensions were scored from the previous day. The total score ranges from 0 to 25. Higher score indicates higher disease activity. | Day 1 and Month 12 | 
| Crohn´s Disease Activity Index (CDAI) Total Score in Participants Who Had Moderate to Severe Active CD at Day 1 and Month 12 | CDAI evaluated the severity of signs and symptoms of CD. Collected data included information on the number of liquid stools, intensity of abdominal pain, general well-being, presence of comorbid conditions, use of medications for diarrhea, physical examination, and laboratory findings (abdominal mass, hematocrit, body weight), yielding 8 items that were combined with data from a 7-day diary to obtain the total CDAI score which ranges from 0 to approximately 600 points, where higher score indicates higher disease activity. | Day 1 and Month 12 | 
| Partial Mayo Score in Participants Who Had Moderate to Severe Active UC at Day 1 and Month 12 | The mayo score without endoscopy measured severity of ulcerative colitis. Three sub-scores for stool frequency, rectal bleeding, and physician's global assessment were each graded from 0 to 3 with higher scores indicating more severe disease. Individual sub-scores were then summed to provide the total score ranging from 0 (normal or inactive disease) to 9 (severe disease). | Day 1 and Month 12 | 
| Percentage of Participants With Moderate to Severe Active CD or UC Who Changed IBD Treatment at Month 12, by Reason | One participant could have more than one reason for discontinuation. | Month 12 | 
| Quality of Life as Assessed by European Quality of Life 5-Dimension (EQ-5D) Health States Visual Analog Scale (VAS) Score at Day 1 | EQ-5D questionnaire is an instrument used to measure general HRQOL in participants with IBD. Each dimension has three possible levels: 1 = none, 2 = moderate or 3 = extreme. The EQ-5D VAS score is a self-assigned rating of overall health using a 20-cm visual, vertical scale, with a score of 0 as the worst and 100 as the best possible health. An increase of ≥7 points in the EQ-5D VAS score represents a clinically meaningful improvement in quality of life for participants. | Day 1 | 
| Quality of Life as Assessed by 36-Item Short Form Health Survey (SF-36) Component Score at Day 1 | The Short Form-36 (SF-36) is a questionnaire that evaluates a participant's health related quality of life. SF-36 includes 36 questions related to 8 health dimensions: physical functioning, role-physical (role limitations due to physical health problems), bodily pain, general health, vitality (energy/fatigue), social functioning, role-emotional (role limitations due to emotional problems), and mental health. Based on these 4 scales (physical functioning, role-physical, bodily pain, general health), the physical component summary (PCS) score is generated which ranges between 0 and 100, with higher scores indicating a better quality of life. Based on these 4 scales (vitality, social functioning, role-emotional, and mental health), the mental component summary (MCS) score is generated which ranges between 0 and 100, with higher scores indicating a better quality of life. | Day 1 | 
| Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Day 1 | The Inflammatory Bowel Disease Questionnaire (IBDQ) was a 32-item questionnaire that measures 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. Within dimensions, each question presented seven possible answers/points. Each domain score was the sum of 8 responses each ranging from 1 to 7, where 1 indicated worst function and 7 the best. The total score ranged from 32 to 224, with higher scores representing better quality of life. The IBDQ was not validated for participants with colostomies and therefore was not be applied for these participants. | Day 1 | 
| Inflammatory Bowel Disease Questionnaire (IBDQ) Domain Score at Day 1 | The Inflammatory Bowel Disease Questionnaire (IBDQ) was a 32-item questionnaire that measures 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. Within dimensions, each question presented seven possible answers/points. Each domain score was the average of 8 responses each ranging from 1 to 7, where 1 indicated worst function and 7 the best function. The IBDQ was not validated for participants with colostomies and therefore was not be applied for these participants. | Day 1 | 
| Mean of Percentage of Total Work Impairment Due to CD as Assessed by Work Productivity and Activity Impairment (WPAI) Questionnaire at Day 1 | The Work Productivity and Activity Impairment questionnaire (WPAI) assessed the impact of IBD on work productivity and daily activities during the previous 7 days. The 'impairment while working due to IBD' was calculated based on one question: to what degree did the disease impair the productivity while working in the past seven days from visit and the 'activity impairment' was calculated based on Question: how much did the disease affect ability to perform regular daily activities, other than work at a job? Percentage of overall work impairment due to IBD is calculated as: Absenteeism+(1-Absenteeism)*Presenteeism. The total score ranges from 0 (no impairment) to 100% (total loss of work productivity). | Day 1 | 
| Mean of Percentage of Work Time Missed Due to CD as Assessed by WPAI at Day 1 | Mean total activity impairment due to IBD from WPAI questionnaire was reported. The 'overall work impairment due to IBD' was calculated based on three items: (Q2) the number of hours missed from work due to health problems in the past seven days; (Q4) the number of actual work hours in the past seven days; and (Q5) to what degree did the disease impair the productivity while working past seven days. The data was calculated using the formula Q2/(Q2+Q4)+[(1-(Q2/(Q2+Q4))x(Q5/10)] and converted to percent. Data are presented as impairment percentage, with higher numbers indicating greater impairment and less productivity. | Day 1 | 
| Mean of Percentage of Impairment While Working Due to CD as Assessed by WPAI at Day 1 | Mean impairment while working due to IBD from WPAI questionnaire was reported. The 'impairment while working due to IBD' was calculated based on one item: (Q5) to what degree did the disease impair the productivity while working in the past seven days. The item was measured on a scale from 0 (no effect) to 10 (completely prevented from doing regular activities/ working). The data was calculated using the formula Q5/10 and converted to percent. ata are presented as impairment percentage, with higher numbers indicating greater impairment and less productivity. | Day 1 | 
| Mean of Percentage of Total Activity Impairment Due to CD as Assessed by WPAI | Mean total activity impairment due to IBD from WPAI questionnaire was reported. The 'overall work impairment due to IBD' was calculated based on three items: (Q2) the number of hours missed from work due to health problems in the past seven days; (Q4) the number of actual work hours in the past seven days; and (Q5) to what degree did the disease impair the productivity while working past seven days. The data was calculated using the formula Q2/(Q2+Q4)+[(1-(Q2/(Q2+Q4))x(Q5/10)] and converted to percent. Data are presented as impairment percentage, with higher numbers indicating greater impairment and less productivity. | Day 1 | 
| Percentage of Participants Who Used Healthcare Resources | Healthcare resources used in the previous 3 years included imaging and laboratory testing, surgeries, hospitalizations, and consultations. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy