A Study to Observe Vedolizumab and Anti-tumour Necrosis Factors (Anti-TNFs) Outcomes in Real-world Biologic Ulcerative Colitis (UC) and Crohn's Disease (CD) Participants
- Conditions
- Crohn DiseaseColitis, Ulcerative
- Registration Number
- NCT03710486
- Lead Sponsor
- Takeda
- Brief Summary
The purpose of this study is to describe treatment patterns associated with first-line and second line biologic use (vedolizumab or other biologic) and to describe the real-world clinical effectiveness of the use (first-line and second line) vedolizumab versus other biologics at least 6 months post-treatment initiation.
- Detailed Description
This is a retrospective, non-interventional study of participants with CD or UC. The study will review the medical charts of participants who have initiated the first or second line treatment with vedolizumab or another biologic agent (infliximab, adalimumab, or golimumab \[UC only\]) (index event) during the eligibility period to evaluate the treatment effectiveness, treatment patterns, health care utilization and safety of vedolizumab, and to provide the real-world treatment landscape with anti-TNF alpha therapies.
The study will enroll approximately 400 participants, with 200 participants in each treatment cohort. All participants will be enrolled into two observational groups:
* Cohort 1: Vedolizumab
* Cohort 2: Other Biologics
The data for participants will be collected in two main periods:
* Pre-index Event Period: From the data of diagnosis of UC/CD until one day prior to the date when vedolizumab or other biologic treatment was initiated during the eligibility period.
* Post-index Event Period: From the date when vedolizumab or other biologic treatment was initiated during the eligibility period until the earliest of 6 months (post-index treatment discontinuation, death of participants, lost-to-follow up, or date of chart abstraction initiation.
This multi-center trial will be conducted in Spain and Portugal. The overall time for data collection in the study will be approximately 12 months and the overall duration of the study is approximately 24 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 409
- Has a diagnosis of moderate to severe UC or CD documented in the medical chart.
- Received at least one dose of vedolizumab or other biologic (infliximab, adalimumab, or golimumab [UC only]) during the eligibility period.
- Received the biologic treatment as first-line or second line biologic for UC or CD.
- Has a minimum of six months of follow-up between date of starting biologic therapy (index event) and the date of completion of the participant pre-selection registry.
- Received vedolizumab or another biologic as part of an interventional clinical trial ever in their lifetime (includes index treatment).
- Index treatment was another biologic therapy other than vedolizumab, infliximab, adalimumab, or golimumab (UC only).
- Initiated index treatment as combination therapy with two biologic agents.
- The biologic was prescribed for treatment of perianal disease.
- Received biologic therapy before the index period for a disease other than inflammatory bowel disease.
- Medical chart is unavailable.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Discontinued Index Therapy for UC Participants From the date of diagnosis of UC (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Index treatment is defined as the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Number of Participants Who Discontinue Index Treatment in Vedolizumab Cohort and Initiated Second-line Biologic Within 6 Months Post-index Treatment Discontinuation From the date of diagnosis of CD or UC (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Index treatment is defined as the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With Biochemical Remission Based on CRP at 14 Weeks for UC Participants At 14 weeks post-index (assessment time window >0 to 38 weeks) Biochemical remission based on CRP was defined as CRP level \<5 mg/L. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside \>0 to 38 weeks time window was considered for 14 weeks assessment and were reported in this outcome measure.
Time to Switching for Vedolizumab Participants From the date of diagnosis of CD or UC (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Time to switching was defined as time from index treatment initiation until a participant initiated another biologic treatment (Vedolizumab, infliximab, adalimumab, or golimumab \[UC only\], tofacitinib, certolizumab and ustekinumab). Index treatment is defined as the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With Clinical Response at 52 Weeks for UC Participants At 52 weeks post-index (assessment time window 46 to 58 weeks) Clinical response in UC participants was evaluated using partial mayo score. Partial mayo score consisted of 3 sub-scores: stool pattern, most severe rectal bleeding of the day, and global assessment by physician, each graded from 0 to 3. These scores were summed to give a total score range of 0 to 9. Where, higher scores indicate more severe disease. The clinical response was defined as partial mayo score of \<4 or reduction of \>= 2 points in scores from index date or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 46 to 58 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Number of Participants With Reasons for Treatment Modifications in UC Participants From the date of diagnosis of UC (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With Clinical Response at 52 Weeks for CD Participants At 52 weeks post-index (assessment time window 46 to 58 weeks) Clinical response in CD participants was evaluated using HBI scale. HBI scale consisted of clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools per day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. Clinical response was defined as HBI score of \<=4 or reduction of \>=3 points in scores from index date or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With One or More Treatment Intensifications for CD Participants From the date of diagnosis of CD (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Index treatment is the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. Dose intensification was performed by shortening the interval between doses in most cases in all the subgroups.
Number of Participants With Reasons for Treatment Modifications in CD Participants From the date of diagnosis of CD (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With One or More Treatment Intensifications for UC Participants From the date of diagnosis of UC (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Index treatment is the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. Dose intensification was performed by shortening the interval between doses in most cases in all the subgroups.
Percentage of Participants Who Discontinued Index Therapy for CD Participants From the date of diagnosis of CD (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Index treatment is defined as the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Time to Discontinuation for CD Participants From the date of diagnosis of CD (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Time to discontinuation was defined as time from index treatment initiation until participant discontinued index treatment without switching to another biologic therapy. Time to discontinuation was estimated with Kaplan-Meier method adjusted by PS-IPTW. Index treatment is defined as the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Time to Discontinuation for UC Participants From the date of diagnosis of UC (within previous 2 years) including index date until post-index treatment discontinuation, death, loss to follow up, or date of chart abstraction initiation (approximately 6 months post index date) Time to discontinuation was defined as time from index treatment initiation until participant discontinued index treatment without switching to another biologic therapy. Time to discontinuation was estimated with Kaplan-Meier method adjusted by PS-IPTW. Index treatment is defined as the first or second line treatment with vedolizumab or other biologics. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With Biochemical Remission Based on CRP at 52 Weeks for UC Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Biochemical remission based on CRP was defined as CRP level of \<5 mg/L. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 28 to 76 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Biochemical Remission Based on FCP at 14 Weeks for UC Participants At 14 weeks post-index (assessment time window >0 to 38 weeks) Biochemical remission based on FCP was defined as FCP level of \<250 mcg/g. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside \>0 to 38 weeks time window was considered for 14 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Clinical Response at 14 Weeks for CD Participants At 14 weeks post-index (assessment time window 10 to 18 weeks) Clinical response in CD participants was evaluated using Harvey-Bradshaw index (HBI) scale. HBI scale consisted of clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools per day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. Clinical response was defined as HBI score less than or equal to (\<=) 4 or reduction of greater than or equal to (\>=) 3 points in scores from index date or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With Clinical Remission at 52 Weeks for UC Participants At 52 weeks post-index (assessment time window 46 to 58 weeks) Clinical remission in UC participants was evaluated using partial mayo score. Partial mayo score consisted of 3 sub-scores: stool pattern, most severe rectal bleeding of the day, and global assessment by physician, each graded from 0 to 3. These scores were summed to give a total score range of 0 to 9. Where, higher scores indicate more severe disease. Clinical remission was defined as partial mayo score of \<2 or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 46 to 58 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Biochemical Remission Based on FCP at 52 Weeks for CD Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Biochemical remission based on FCP was defined as FCP level of \<250 mcg/g. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 28 to 76 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Clinical Response at 14 Weeks for UC Participants At 14 weeks post-index (assessment time window 10 to 18 weeks) Clinical response in UC participants was evaluated using partial mayo score. Partial mayo score consisted of 3 sub-scores: stool pattern, most severe rectal bleeding of the day, and global assessment by physician, each graded from 0 to 3. These scores were summed to give a total score range of 0 to 9. Where, higher scores indicate more severe disease. Clinical response was defined as partial mayo score of less than (\<) 4 or reduction of \>= 2 points in scores from index date or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 10 to 18 weeks time window was considered for 14 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Biochemical Remission Based on CRP at 52 Weeks for CD Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Biochemical remission based on CRP was defined as CRP level of \<5 mg/L. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 28 to 76 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Clinical Remission at 14 Weeks for CD Participants At 14 weeks post-index (assessment time window 10 to 18 weeks) Clinical remission in CD participants was evaluated using HBI scale. HBI scale consisted of clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools per day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. Clinical remission was defined as HBI score of \<=4 or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 10 to 18 weeks time window was considered for 14 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Clinical Remission at 52 Weeks for CD Participants At 52 weeks post-index (assessment time window 46 to 58 weeks) Clinical remission in CD participants was evaluated using HBI scale. HBI scale consisted of clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools per day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. Clinical remission was defined as HBI score of \<=4 or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 46 to 58 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Clinical Remission at 14 Weeks for UC Participants At 14 weeks post-index (assessment time window 10 to 18 weeks) Clinical remission in UC participants was evaluated using partial mayo score. Partial mayo score consisted of 3 sub-scores: stool pattern, most severe rectal bleeding of the day, and global assessment by physician, each graded from 0 to 3. These scores were summed to give a total score range of 0 to 9. Where, higher scores indicate more severe disease. Clinical remission was defined as partial mayo score of \<2 or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 10 to 18 weeks time window was considered for 14 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Biochemical Remission Based on C-reactive Protein (CRP) at 14 Weeks for CD Participants At 14 weeks post-index (assessment time window >0 to 38 weeks) Biochemical remission based on CRP was defined as CRP level of \<5 milligram per liter (mg/L). Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside greater than (\>) 0 to 38 weeks time window was considered for 14 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Biochemical Remission Based on Fecal Calprotectin (FCP) at 14 Weeks for CD Participants At 14 weeks post-index (assessment time window >0 to 38 weeks) Biochemical remission based on FCP was defined as FCP level of \<250 microgram per gram (mcg/g). Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside \>0 to 38 weeks time window was considered for 14 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Biochemical Remission Based on FCP at 52 Weeks for UC Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Biochemical remission based on FCP was defined as FCP level of \<250 mcg/g. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 28 to 76 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Endoscopic Remission at 52 Weeks for CD Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Endoscopic remission for CD participants was evaluated using SES-CD score. The SES-CD evaluated 4 endoscopic variables (ulcer size, percentage of the surface area that was ulcerated, percentage of the surface area affected, and stenosis in 5 segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD score \<=2 or based on physician assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 28 to 76 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Endoscopic Remission at 52 Weeks for UC Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Endoscopic remission in UC participants is based on investigator assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 28 to 76 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
Percentage of Participants With Endoscopic Response at 52 Weeks for CD Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Endoscopic response for CD participants was evaluated using simple endoscopic index for Crohn's disease (SES-CD) score. SES-CD evaluated 4 endoscopic variables (ulcer size, percentage of the surface area that was ulcerated, percentage of the surface area affected, and stenosis in 5 segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD score \<=2 or based on physician assessment (for UC and CD both). SES-CD score at index date \>0 relative difference was calculated (100\*\[Index date-52 weeks assessment\]/Index date) and relative difference of \>= 50% was considered response. Index date was defined as the date when vedolizumab or other biologic treatment was initiated.
Percentage of Participants With Endoscopic Response at 52 Weeks for UC Participants At 52 weeks post-index (assessment time window 28 to 76 weeks) Endoscopic response in UC participants is based on investigator assessment. Index date was defined as the date when vedolizumab or other biologic treatment was initiated. As pre-specified in the SAP, the data inside 28 to 76 weeks time window was considered for 52 weeks assessment and were reported in this outcome measure.
- Secondary Outcome Measures
Name Time Method Incidence Rate of Adverse Events and Serious Adverse Events Index event period up to 6 months post-index treatment discontinuation Incidence rate was based on per 100 participants-year. Index event period was defined as the period of time within which participants with UC or CD initiated first or second line treatment with vedolizumab or other biologic.
Percentage of Participants With Related Treatment Adverse Events and Related Treatment Serious Adverse Events Index event period up to 6 months post-index treatment discontinuation Index event period was defined as the period of time within which participants with UC or CD initiated first or second line treatment with vedolizumab or other biologic. Percentage of participants with treatment related adverse events and related treatment serious adverse events were reported.
Incidence Rate of Related Treatment Adverse Events and Related Treatment Serious Adverse Events Index event period up to 6 months post-index treatment discontinuation Incidence rate was based on per 100 participant-year. Index event period was defined as the period of time within which participants with UC or CD initiated first or second line treatment with vedolizumab or other biologic.
Percentage of Participants With Adverse Events and Serious Adverse Events Index event period up to 6 months post-index treatment discontinuation Index event period was defined as the period of time within which participants with UC or CD initiated first or second line treatment with vedolizumab or other biologic. The PS-IPTW method was used for balancing the cohorts. Percentage of participants determined after applying this method are reported in 'Adverse events' and 'Serious adverse events' categories in this outcome measure.
Incidence Rate of Infections, Serious Infections and Malignancies Index event period up to 6 months post-index treatment discontinuation Incidence rate was based on per 100 participant-year. Index event period was defined as the period of time within which participants with UC or CD initiated first or second line treatment with vedolizumab or other biologic.
Percentage of Participants With Infections, Serious Infections and Malignancies Index event period up to 6 months post-index treatment discontinuation Index event period was defined as the period of time within which participants with UC or CD initiated first or second line treatment with vedolizumab or other biologic. Percentage of participants with infections, serious infections and malignancies were reported.
Trial Locations
- Locations (26)
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Comunidad Valenciana, Spain
Centro Hospitalar Universitario Lisboa Norte - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Hospital Beatriz Angelo
🇵🇹Loures, Lisboa, Portugal
Hospital do Espirito Santo de Evora
🇵🇹Evora, Portugal
Centro Hospitalar de Entre Douro e Vouga
🇵🇹Santa Maria da Feira, Aveiro, Portugal
Hospital Universitario Central de Asturias (HUCA)
🇪🇸Oviedo, Asturias, Spain
Hospital Universitari Son Espases
🇪🇸Palma, Islas Baleares, Spain
Hospital Distrital de Santarem
🇵🇹Santarem, Portugal
Hospital Universitario de Leon
🇪🇸Leon, Castilla Y Leon, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Castilla Y Leon, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Cataluna, Spain
Hospital de Sant Joan Despi - Moises Broggi
🇪🇸Barcelona, Cataluna, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitari Parc Tauli
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitari de Girona Doctor Josep Trueta
🇪🇸Girona, Cataluna, Spain
Hospital de La Princesa
🇪🇸Madrid, Comunidad De Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Comunidad De Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Comunidad De Madrid, Spain
Hospital Universitario de La Paz
🇪🇸Madrid, Comunidad De Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Comunidad De Madrid, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Comunidad Valenciana, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Comunidad De Madrid, Spain
Hospital de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Comunidad Valenciana, Spain
Hospital de Manises
🇪🇸Valencia, Comunidad Valenciana, Spain
Hospital Universitario de Canarias
🇪🇸Santa Cruz de Tenerife, Islas Canarias, Spain