Colitis, Ulcerative, Crohn Disease, Inflammatory Bowel Diseases
Conditions
Keywords
Drug Therapy
Brief summary
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
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.
Interventions
OTHERNo Intervention
As this was an observational study, no intervention was administered.
Sponsors
Takeda
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Received or receiving vedolizumab between the years 2015 and 2020.
Exclusion criteria
No
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TDM Cohort: Correlation Between Week 6 Vedolizumab TDM and Week 30 Faecal Calprotectin (FCP) | After the first dose of vedolizumab (at Week 30) | The relationship between vedolizumab TDM at Week 6 and FCP levels at Week 30 were studied using univariate and multivariate logistic regression models. Multivariate analyses were 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 was used as a surrogate marker for disease severity, and by extension drug efficacy. The FCP level was detected in participant's stool 30 weeks after the participant's first dose of vedolizumab. FCP was treated as a continuous variable for correlation analysis to determine Spearman's correlation coefficient. This outcome measure was planned to be analyzed only in participants enrolled in the TDM Cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TDM Cohort: C-reactive Protein (CRP) Level at Week 30 | After the first dose of vedolizumab (at Week 30) | The CRP level were detected in participant's blood 30 weeks after the participant's first dose of vedolizumab. CRP was used as a surrogate marker for disease severity, and by extension drug efficacy. This outcome measure was planned to be analyzed separately in participants with UC and CD who were collectively a part of the TDM Cohort. |
| TDM Cohort: Disease Score for Crohn's Disease (CD) Participants Based on Harvey-Bradshaw Index (HBI) at Week 30 | After the first dose of vedolizumab (at Week 30) | Disease activity scores of CD participants were based on HBI. It consists of clinical parameters: general well-being (0 = 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 \<5 = remission, 5 to 7 = mild disease activity, 8 to 16 = moderate disease activity and \>16 = severe disease activity. This outcome measure was planned to be analyzed only in participants with CD. |
| TDM Cohort: Disease Score for Ulcerative Colitis (UC) Participants Based on Partial Mayo Score at Week 30 | After the first dose of vedolizumab (at Week 30) | Disease activity scores of UC participants were 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 indicate more severe disease. This outcome measure was planned to be analyzed only in participants with UC. |
| Number of Participants Categorized Based on Dose Escalation | Baseline (Week 0) up to Week 30 (after first dose of vedolizumab) | Dose escalation was defined as a change from doses every 8 weeks to every 4 weeks. |
| TDM Cohort: Number of Participants Categorized Based on Treatment Persistence at the End of the TDM Study at Week 30 | After the first dose of vedolizumab (at Week 30) | Treatment persistence was defined as whether the participant was still on the treatment at the end of the TDM study. This outcome measure was planned to be analyzed only in participants enrolled in the TDM Cohort. |
| Treatment Duration | From treatment initiation up to discontinuation of treatment or up to data extraction date Oct 2020), whichever occurs first (maximum up to approximately 5 years) | Treatment duration was defined as the length of time a participant remains on treatment (i.e., from the year 2015 to 2020). |
Countries
Canada
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Canada from 05 October 2020 to 22 September 2021.
Pre-assignment details
Data of participants diagnosed with moderate to severe inflammatory bowel disease (IBD)- Crohn's disease (CD) or ulcerative colitis (UC) was analyzed retrospectively in this observational study. Total of 7873 participants entered the patient support program, out of which 5194 participants met study criteria, had non-missing therapeutic drug monitoring (TDM) Week 6 values, and were analyzed.
Participants by arm
| Arm | Count |
|---|---|
| TDM Cohort Participants diagnosed with IBD (UC or CD) within Takeda Canada Patient Support Program (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 along with the biomarker testing and therapeutic drug monitoring (TDM) at pre-specified intervals during their treatment were observed retrospectively. | 436 |
| Historical Cohort 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 were observed retrospectively. | 4,758 |
| Total | 5,194 |
Baseline characteristics
| Characteristic | TDM Cohort | Historical Cohort | Total |
|---|---|---|---|
| Age, Customized 18 Years and Above | 436 Participants | 4758 Participants | 5194 Participants |
| Age, Customized Less Than 18 Years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Canada | 436 Participants | 4758 Participants | 5194 Participants |
| Sex: Female, Male Female | 221 Participants | 2370 Participants | 2591 Participants |
| Sex: Female, Male Male | 215 Participants | 2388 Participants | 2603 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 436 | 0 / 4,758 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
TDM Cohort: Correlation Between Week 6 Vedolizumab TDM and Week 30 Faecal Calprotectin (FCP)
The relationship between vedolizumab TDM at Week 6 and FCP levels at Week 30 were studied using univariate and multivariate logistic regression models. Multivariate analyses were 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 was used as a surrogate marker for disease severity, and by extension drug efficacy. The FCP level was detected in participant's stool 30 weeks after the participant's first dose of vedolizumab. FCP was treated as a continuous variable for correlation analysis to determine Spearman's correlation coefficient. This outcome measure was planned to be analyzed only in participants enrolled in the TDM Cohort.
Time frame: After the first dose of vedolizumab (at Week 30)
Population: Analyzed participants included all participants who were not screen failures, met all the inclusion criteria and had enough information about response to the biological treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TDM Cohort | TDM Cohort: Correlation Between Week 6 Vedolizumab TDM and Week 30 Faecal Calprotectin (FCP) | -0.23 correlation coefficient |
p-value: =0.003Spearman's Rank Correlation
Secondary
Number of Participants Categorized Based on Dose Escalation
Dose escalation was defined as a change from doses every 8 weeks to every 4 weeks.
Time frame: Baseline (Week 0) up to Week 30 (after first dose of vedolizumab)
Population: Analyzed participants included all participants who were not screen failures, met all the inclusion criteria and had enough information about response to the biological treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TDM Cohort | Number of Participants Categorized Based on Dose Escalation | 173 Participants |
| TDM Cohort: Crohn's Disease | Number of Participants Categorized Based on Dose Escalation | 852 Participants |
p-value: <0.001Log Rank
Secondary
TDM Cohort: C-reactive Protein (CRP) Level at Week 30
The CRP level were detected in participant's blood 30 weeks after the participant's first dose of vedolizumab. CRP was used as a surrogate marker for disease severity, and by extension drug efficacy. This outcome measure was planned to be analyzed separately in participants with UC and CD who were collectively a part of the TDM Cohort.
Time frame: After the first dose of vedolizumab (at Week 30)
Population: Analyzed participants included all participants who were not screen failures, met all the inclusion criteria and had enough information about response to the biological treatment. Overall number analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDM Cohort | TDM Cohort: C-reactive Protein (CRP) Level at Week 30 | 2 mg/L |
| TDM Cohort: Crohn's Disease | TDM Cohort: C-reactive Protein (CRP) Level at Week 30 | 3 mg/L |
p-value: =0.25Log Rank
Secondary
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 were based on HBI. It consists of clinical parameters: general well-being (0 = 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 \<5 = remission, 5 to 7 = mild disease activity, 8 to 16 = moderate disease activity and \>16 = severe disease activity. This outcome measure was planned to be analyzed only in participants with CD.
Time frame: After the first dose of vedolizumab (at Week 30)
Population: Analyzed participants included all participants who were not screen failures, met all the inclusion criteria and had enough information about response to the biological treatment. Overall number analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDM Cohort | TDM Cohort: Disease Score for Crohn's Disease (CD) Participants Based on Harvey-Bradshaw Index (HBI) at Week 30 | 3 score on a scale |
Secondary
TDM Cohort: Disease Score for Ulcerative Colitis (UC) Participants Based on Partial Mayo Score at Week 30
Disease activity scores of UC participants were 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 indicate more severe disease. This outcome measure was planned to be analyzed only in participants with UC.
Time frame: After the first dose of vedolizumab (at Week 30)
Population: Analyzed participants included all participants who were not screen failures, met all the inclusion criteria and had enough information about response to the biological treatment. Overall number analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDM Cohort | TDM Cohort: Disease Score for Ulcerative Colitis (UC) Participants Based on Partial Mayo Score at Week 30 | 1 score on a scale |
Secondary
TDM Cohort: Number of Participants Categorized Based on Treatment Persistence at the End of the TDM Study at Week 30
Treatment persistence was defined as whether the participant was still on the treatment at the end of the TDM study. This outcome measure was planned to be analyzed only in participants enrolled in the TDM Cohort.
Time frame: After the first dose of vedolizumab (at Week 30)
Population: Analyzed participants included all participants who were not screen failures, met all the inclusion criteria and had enough information about response to the biological treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TDM Cohort | TDM Cohort: Number of Participants Categorized Based on Treatment Persistence at the End of the TDM Study at Week 30 | Did not Persist on Treatment | 76 Participants |
| TDM Cohort | TDM Cohort: Number of Participants Categorized Based on Treatment Persistence at the End of the TDM Study at Week 30 | Treatment Persistence | 360 Participants |
Secondary
Treatment Duration
Treatment duration was defined as the length of time a participant remains on treatment (i.e., from the year 2015 to 2020).
Time frame: From treatment initiation up to discontinuation of treatment or up to data extraction date Oct 2020), whichever occurs first (maximum up to approximately 5 years)
Population: Analyzed participants included all participants who were not screen failures, met all the inclusion criteria and had enough information about response to the biological treatment. Overall number analyzed are the number of participants with data available for analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TDM Cohort | Treatment Duration | 378.0 days |
| TDM Cohort: Crohn's Disease | Treatment Duration | 242.0 days |
p-value: <0.0001Log Rank