Trial Outcomes & Findings for Study of Relationship Between Vedolizumab Therapeutic Drug Monitoring, Biomarkers of Inflammation and Clinical Outcomes (NCT NCT04567628)
NCT ID: NCT04567628
Last Updated: 2024-03-15
Results Overview
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.
COMPLETED
7873 participants
After the first dose of vedolizumab (at Week 30)
2024-03-15
Participant Flow
Participants took part in the study at 1 investigative site in Canada from 05 October 2020 to 22 September 2021.
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
436
|
4758
|
|
Overall Study
COMPLETED
|
436
|
4758
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
TDM Cohort
n=436 Participants
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.
|
Historical Cohort
n=4758 Participants
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.
|
Total
n=5194 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Less Than 18 Years
|
0 Participants
n=436 Participants
|
0 Participants
n=4758 Participants
|
0 Participants
n=5194 Participants
|
|
Age, Customized
18 Years and Above
|
436 Participants
n=436 Participants
|
4758 Participants
n=4758 Participants
|
5194 Participants
n=5194 Participants
|
|
Sex: Female, Male
Female
|
221 Participants
n=436 Participants
|
2370 Participants
n=4758 Participants
|
2591 Participants
n=5194 Participants
|
|
Sex: Female, Male
Male
|
215 Participants
n=436 Participants
|
2388 Participants
n=4758 Participants
|
2603 Participants
n=5194 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Canada
|
436 Participants
n=436 Participants
|
4758 Participants
n=4758 Participants
|
5194 Participants
n=5194 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
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.
|
TDM Cohort: Crohn's Disease
n=436 Participants
Participants diagnosed with IBD (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 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.
|
|---|---|---|
|
TDM Cohort: Correlation Between Week 6 Vedolizumab TDM and Week 30 Faecal Calprotectin (FCP)
|
—
|
-0.23 correlation coefficient
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Historical Cohort
n=119 Participants
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.
|
TDM Cohort: Crohn's Disease
n=91 Participants
Participants diagnosed with IBD (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 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.
|
|---|---|---|
|
TDM Cohort: C-reactive Protein (CRP) Level at Week 30
|
3 mg/L
Interval 1.0 to 6.0
|
2 mg/L
Interval 1.0 to 5.0
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
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.
|
TDM Cohort: Crohn's Disease
n=67 Participants
Participants diagnosed with IBD (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 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.
|
|---|---|---|
|
TDM Cohort: Disease Score for Crohn's Disease (CD) Participants Based on Harvey-Bradshaw Index (HBI) at Week 30
|
—
|
3 score on a scale
Interval 1.0 to 6.0
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
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.
|
TDM Cohort: Crohn's Disease
n=46 Participants
Participants diagnosed with IBD (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 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.
|
|---|---|---|
|
TDM Cohort: Disease Score for Ulcerative Colitis (UC) Participants Based on Partial Mayo Score at Week 30
|
—
|
1 score on a scale
Interval 0.0 to 3.0
|
SECONDARY outcome
Timeframe: 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.
Dose escalation was defined as a change from doses every 8 weeks to every 4 weeks.
Outcome measures
| Measure |
Historical Cohort
n=4758 Participants
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.
|
TDM Cohort: Crohn's Disease
n=436 Participants
Participants diagnosed with IBD (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 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.
|
|---|---|---|
|
Number of Participants Categorized Based on Dose Escalation
|
852 Participants
|
173 Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
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.
|
TDM Cohort: Crohn's Disease
n=436 Participants
Participants diagnosed with IBD (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 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.
|
|---|---|---|
|
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: Number of Participants Categorized Based on Treatment Persistence at the End of the TDM Study at Week 30
Treatment Persistence
|
—
|
360 Participants
|
SECONDARY outcome
Timeframe: 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.
Treatment duration was defined as the length of time a participant remains on treatment (i.e., from the year 2015 to 2020).
Outcome measures
| Measure |
Historical Cohort
n=4758 Participants
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.
|
TDM Cohort: Crohn's Disease
n=436 Participants
Participants diagnosed with IBD (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 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.
|
|---|---|---|
|
Treatment Duration
|
242.0 days
Interval 116.0 to 437.5
|
378.0 days
Interval 238.0 to 553.5
|
Adverse Events
TDM Cohort
Historical Cohort
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER