A Prospective Non-interventional Multicenter Study to Evaluate the Effectiveness of Adalimumab in Korean Patients With Ulcerative Colitis (UC) and Identify Potential Predictors of Clinical Response in Routine Clinical Practice

Study Overview
=================
Brief Summary
-----------------
This is a prospective, single country, multi-center study in participants with ulcerative colitis (UC) treated with adalimumab. Up to 147 participants are enrolled at approximately 20 sites. The baseline assessment is performed prior to the first dose of adalimumab (Visit 1). Study visits are conducted at weeks 8, 16, 24, 32, 40, 48 and 56 after baseline in accordance with clinical practice. All participants will have one Follow-up for safety approximately 70 days after the last dose of adalimumab.

Detailed Description
-----------------
This is a prospective, single-country, multi-center study in UC patients treated with adalimumab. The prescription of adalimumab is at the discretion of the physician in accordance with clinical practice and label, is made independently from this study, and preceded the decision to offer the patient the opportunity to participate in this study. Up to 147 subjects are planned to be enrolled at approximately 20 sites. The baseline assessment is performed prior to the first dose of adalimumab (Visit 1). Participants are administered adalimumab 160 mg at Week 0, 80 mg at Week 2, and then 40 mg every other week per the Korean label. Study visits are conducted at Weeks 8, 16, 24, 32, 40, 48 and 56 after baseline in accordance with clinical practice. All participants had one Follow-up for safety approximately 70 days after the last dose of adalimumab. Clinical response is assessed at Week 8, and participants with clinical response at Week 8 can continue on adalimumab treatment as per Korean reimbursement guidelines. Clinical response is defined as a decrease from baseline in the total Mayo score by at least 3 points and at least 30% with an accompanying decrease in rectal bleeding subscore of at least 1 point or absolute rectal bleeding sub-score of 0 or 1.

Official Title
-----------------
A Prospective Multicenter Study to Observe the Effectiveness on Ulcerative Colitis and Predictive Factors of Clinical Response in Korean Patients Treated With Adalimumab (EUREKA Study)

Conditions
-----------------
Ulcerative Colitis

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be an adult ≥19 years Participant with active moderate to severe ulcerative colitis with Mayo score of ≥ 6 points and endoscopic sub-score of ≥ 2 points despite treatment with corticosteroids and/or immunosuppressants. Participant must have tuberculosis (TB) Screening Assessment in accordance Korean reimbursement guidelines. Participants who had started on adalimumab treatment in normal clinical practice setting by their physician. Participant must provide written authorization form to use personal and/or health data prior to the entry into the study. Exclusion Criteria: Female participants who are pregnant or breast feeding Participant with any contraindication to adalimumab Participant that is participating in other clinical trials

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Ulcerative Colitis (UC)<br>Adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every other week per the Korean label in participants with active moderate-to-severe UC. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Week 8 Responders With Durable Clinical Response at Week 56 | Durable clinical response was defined as reduction in complete Full Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at both Week 8 and 56. Clinical response was defined as reduction in complete full Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment [PGA]), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 
| Percentage of Participants With Clinical Response at Week 8 | Clinical response was defined as reduction in complete full Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 8 | 
| Percentage of Participants With Clinical Response at Week 24 | Clinical response was defined as reduction in complete full Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at Week 24. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 24 | 
| Percentage of Participants With Clinical Response at Week 56 | Clinical response was defined as reduction in complete full Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at Week 56. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Remission at Week 8 | Clinical remission was defined as the full Mayo score ≤2 points, with no individual sub-score exceeding 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 8 | 
| Percentage of Participants With Clinical Remission at Week 56 | Clinical remission was defined as the full Mayo score ≤2 points, with no individual sub-score exceeding 1 point at Week 56. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 
| Percentage of Participants Who Were Week 8 Responders With Clinical Remission at Week 8 | Clinical remission was defined as the full Mayo score ≤2 points, with no individual sub-score exceeding 1 point at Week 8. Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 8 | 
| Percentage of Participants Who Were Week 8 Responders With Clinical Remission at Week 56 | Clinical remission was defined as the full Mayo score ≤2 points, with no individual sub-score exceeding 1 point at Week 56. Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 
| Percentage of Participants With Steroid-free Remission at Week 8 | Steroid free remission was defined as participants who were in remission without the use of systemic steroids from Visit 1 (Baseline) prior to assessment. | Week 8 | 
| Percentage of Participants With Steroid-free Remission at Week 56 | Steroid free remission was defined as participants who were in remission without the use of systemic steroids within the past 12 weeks prior to assessment. | Week 56 | 
| Percentage of Participants Who Were Week 8 Responders With Steroid-free Remission at Week 8 | Steroid-free remission was defined as participants who were in remission without the use of systemic steroids within the past 12 weeks prior to assessment. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 8 | 
| Percentage of Participants Who Were Week 8 Responders With Steroid-free Remission at Week 56 | Steroid free remission was defined as participants who were in remission without the use of systemic steroids within the past 12 weeks prior to assessment. Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 
| Percentage of Participants With Steroid-free Response at Week 8 | Steroid-free response was defined as participants who were in clinical response without the use of systemic steroids within the past 8 weeks prior to assessment. Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 8 | 
| Percentage of Participants With Steroid-free Response at Week 56 | Steroid-free response was defined as participants who were in clinical response without the use of systemic steroids within the past 8 weeks prior to assessment. Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 
| Percentage of Participants Who Were Week 8 Responders With Steroid-free Response at Week 8 | Steroid free response was defined as participants who were in clinical response without the use of systemic steroids within the past 8 weeks prior to assessment (in Week 8 clinical responders).Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 8 | 
| Percentage of Participants Who Were Week 8 Responders With Steroid-free Response at Week 56 | Steroid free response was defined as participants who were in clinical response without the use of systemic steroids within the past 12 weeks prior to assessment (in Week 8 clinical responders). A participant was a Week 8 responder if they had a clinical response at Week 8. Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 
| Percentage of Participants With Mucosal Healing at Week 8 | Mucosal healing was defined as an endoscopy sub-score of 0 or 1 at week 8. Endoscopic findings were scored on a scale from 0 to 3 as follows: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern, mild friability); 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). The higher the score, the more severe the disease. | Week 8 | 
| Percentage of Participants With Mucosal Healing at Week 56 | Mucosal healing was defined as an endoscopy sub-score of 0 or 1 at Week 56. Endoscopic findings were scored on a scale from 0 to 3 as follows: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern, mild friability); 2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). The higher the score, the more severe the disease. | Week 56 | 
| Percentage of Participants Who Were Week 8 Responders With Mucosal Healing at Week 8 | Mucosal healing was defined as an endoscopy sub-score of 0 or 1 at Week 8. Endoscopic findings were scored on a scale from 0 to 3 (higher score, worse disease): 0=Normal or inactive disease; 1=Mild disease (erythema, decreased vascular pattern, mild friability); 2=Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3=Severe disease (spontaneous bleeding, ulceration). Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. Mayo score measures disease activity for ulcerative colitis from 0 (normal or inactive disease) to 12 (severe disease), calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each ranging from 0 (normal) to 3 (severe disease). Negative change in Mayo score indicates improvement. | Week 8 | 
| Percentage of Participants Who Were Week 8 Responders With Mucosal Healing at Week 56 | Mucosal healing was defined as an endoscopy sub-score of 0 or 1 at Week 56. Endoscopic findings were scored on a scale from 0 to 3 (higher score, worse disease): 0=Normal or inactive disease; 1=Mild disease (erythema, decreased vascular pattern, mild friability); 2=Moderate disease (marked erythema, lack of vascular pattern, friability, erosions); 3=Severe disease (spontaneous bleeding, ulceration). Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. Mayo score measures disease activity for ulcerative colitis from 0 (normal or inactive disease) to 12 (severe disease), calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each ranging from 0 (normal) to 3 (severe disease). Negative change in Mayo score indicates improvement. | Week 56 | 
| Change in Partial Mayo Score From Baseline to Week 8 in Participants Who Were Clinical Responders at Week 56 | The partial Mayo score is based on the Mayo score, which is a tool designed to measure disease activity for ulcerative colitis. The partial Mayo score (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in partial Mayo score indicates improvement. | Baseline, Week 8 | 
| Change in Full Mayo Score From Baseline to Week 8 in Participants Who Were Clinical Responders at Week 56 | Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment [PGA]), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Baseline, Week 8 | 
| Change in Full Mayo Score From Baseline to Week 56 in Participants Who Were Clinical Responders at Week 56 | Clinical response was defined as reduction in complete full Mayo score of ≥ 3 points and ≥ 30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment [PGA]), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Baseline, Week 56 | 
| Fecal Calprotectin Level at Week 8 | Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. | Week 8 | 
| Fecal Calprotectin Level at Week 56 | Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. | Week 56 | 
| Fecal Calprotectin Level at Week 8 in Participants Who Were Clinical Responders at Week 8 | Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. | Week 8 | 
| Fecal Calprotectin Level at Week 56 in Participants Who Were Clinical Responders at Week 8 | Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. | Week 56 | 
| Fecal Calprotectin Level at Week 8 in Participants Who Were Clinical Responders at Week 56 | Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Clinical response was defined as reduction in complete full Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and PGA), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 8 | 
| Fecal Calprotectin Level at Week 56 in Participants Who Were Clinical Responders at Week 56 | Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Clinical response was defined as reduction in complete full Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point at Week 8. The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The Mayo score ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment [PGA]), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in Mayo score indicates improvement. | Week 56 | 
| Change in the Composition of Fecal Microbiota From Baseline to Week 8 and Week 56 | Composition of fecal microbiota (16S ribosomal ribonucleic acid (rRNA) gene sequencing) was measured at Week 0, Week 8, and Week 56. Fecal bacterial composition was determined using 16S sequencing. The obtained sequences were analyzed using the Ezbiocloud database and 16S microbiome pipeline to assess composition and diversity. | Week 0, Week 8, Week 56 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fecal microbiota, Adalimumab trough level, Fecal Calprotectin