Study of Relationship Between Vedolizumab Therapeutic Drug Monitoring, Biomarkers of Inflammation and Clinical Outcomes

Study Overview
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Brief Summary
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The purpose of this study is to determine if a relationship exists between Week 6 vedolizumab therapeutic drug monitoring (TDM) and Week 30 Faecal calprotectin (FCP).

Detailed Description
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This is a non-interventional, retrospective, and longitudinal study of participants with IBD (UC or CD) receiving vedolizumab between years 2015 and 2020. The study will determine the real-world evidence of vedolizumab, its relationship with TDM, biomarkers of inflammation, and its effect on clinical outcomes in a real-world setting. This study will enroll approximately 5,500 participants. Participants will be enrolled in 2 cohorts: TDM Cohort and Historical Cohort. The study will have a retrospective data collection of the participants from PSP between the years 2015 and 2020. The study will include longitudinal analysis of data collected in a subset of Takeda Canada PSP, specifically for those participants on vedolizumab, some of which received biomarker testing and TDM at pre-specified intervals during their treatment. This multi-center trial will be conducted in Canada. The overall time for data collection in the study will be approximately 5 years.

Official Title
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The Relationship Between Vedolizumab Therapeutic Drug Monitoring, Biomarkers of Inflammation and Clinical Outcomes in the Real World Setting (VEDO TDM RWE)

Conditions
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Inflammatory Bowel Diseases, Colitis, Ulcerative, Crohn Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant or, when applicable, the participant's legally acceptable representative signed and dated a written, informed consent form, which specified secondary use of their data, and any required privacy authorization as part of their enrollment in Takeda Canada's PSP. Received or receiving vedolizumab between the years 2015 and 2020. Exclusion Criteria: No exclusion criteria will be applied.

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 |
| --- | --- |
| TDM Cohort<br>Participants diagnosed with inflammatory bowel disease (IBD) (UC or CD) within Takeda Canada Patient Support Program (PSP) group who received treatment with vedolizumab 300 milligram (mg), infusion, intravenously, at Weeks 0, 2, and 6, and every 8 weeks thereafter as per product Health Canada Product Monograph, or every 4 or 6 weeks thereafter as per standard clinical practice between the year 2015 to 2020 along with the biomarker testing and TDM at pre-specified intervals during their treatment will be observed retrospectively. | |
| Historical Cohort<br>Participants diagnosed with IBD (UC or CD) within Takeda Canada PSP group who received treatment with vedolizumab 300 mg, infusion, intravenously, at Weeks 0, 2, and 6, and every 8 weeks thereafter as per product Health Canada Product Monograph, or every 4 or 6 weeks thereafter as per standard clinical practice between the year 2015 to 2020 but did not undergo biomarker testing or TDM during their treatment will be observed retrospectively. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TDM Cohort: Correlation Between Week 6 Vedolizumab TDM and Week 30 FCP | The relationship between vedolizumab TDM at Week 6 and FCP levels at Week 30 will be studied using univariate and multivariate logistic regression models. Multivariate analyses will be performed to control for possible confounding factors such as age, sex, disease type (CD/UC), duration, prior immunomodulator/biologic therapy, vedolizumab start and end dates, vedolizumab dose, vedolizumab frequency, and albumin. FCP will be used as a surrogate marker for disease severity, and by extension drug efficacy, with higher levels indicating poor drug efficacy, and low to non-detectable levels indicating increased drug efficacy. The FCP level will be detected in participant's stool 30 weeks after the participant's first dose of vedolizumab. | At Week 30 after the first dose of vedolizumab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TDM Cohort: C-reactive Protein (CRP) Level at Week 30 | The CRP level will be detected in participant's blood 30 weeks after the participant's first dose of vedolizumab. CRP will be used as a surrogate marker for disease severity, and by extension drug efficacy, with higher levels indicating poor drug efficacy, and low to non-detectable levels indicating increased drug efficacy. | At Week 30 after the first dose of vedolizumab | 
| TDM Cohort: Disease Score for Crohn's Disease (CD) Participants Based on Harvey-bradshaw Index (HBI) at Week 30 | Disease activity scores of CD participants will be based on HBI. It consists of clinical parameters: general well-being (0 equal to [=] very well to 4 = terrible), abdominal pain (0 = none to 3 = severe), number of liquid or soft stools per day, abdominal mass (0 = none to 3 = definite and tender), and complications (8 items; 1 score per item). The total score is sum of sub scores, where score less than (<) 5 = remission, 5 to 7 = mild disease activity, 8 to 16 = moderate disease activity and greater than (>) 16 = severe disease activity. | At Week 30 after the first dose of vedolizumab | 
| TDM Cohort: Disease Score for Ulcerative Colitis (UC) Participants Based on Partial Mayo Score at Week 30 | Disease activity scores of UC participants will be based on Partial Mayo score. It consists of 3 sub-scores: stool pattern, most severe rectal bleeding of the day, and global assessment by physician, each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher scores indicates more severe disease. | At Week 30 after the first dose of vedolizumab | 
| Number of Participants Categorized Based on Dose Escalation | Dose escalation will be defined as a change from doses every 8 weeks to every 6 or 4 weeks. | Baseline (Week 0) up to Week 30 after first dose of vedolizumab | 
| TDM Cohort: Number of Participants Categorized Based on Treatment Persistence at the end of the TDM Study at Week 30 | Treatment Persistence will be defined whether the participant is still on the treatment at the end of the TDM study. | At Week 30 after the first dose of vedolizumab | 
| Treatment Duration | Treatment duration will be defined as the length of time a participant remains on treatment. | Baseline (Week 0) up to Week 30 after the first dose of vedolizumab | 

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