Crohn Disease
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of a treat to target strategy coupled with early endoscopic assessment versus a clinically driven (routine care) approach in achieving endoscopic response.
Detailed description
Study investigates benefit of treat to target maintenance treatment strategy versus routine care to test hypothesis that 'treat to target' ustekinumab (UST) maintenance treatment strategy coupled with early endoscopic assessment will result in higher endoscopic response rate after 48 weeks of treatment, compared to pragmatic maintenance treatment strategy. It consists of screening (5 weeks); treatment period (Week 0 to 48); extension period (Weeks 48 to 104) and safety follow up visit (16 weeks after last dose). Participants will be given an option to enter ultrasound sub-study to assess intestinal ultrasound (IUS) parameters indicating transmural changes in response to treatment with UST in participants with Crohn's disease. Study treatment will be unaffected by participation in sub-study which is optional for participants of main study.
Interventions
DRUGUstekinumab
Participants will receive IV induction treatment with ustekinumab on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg) IV. At Week 8, all participants will receive a 90 mg SC injection of ustekinumab. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.
Sponsors
Janssen-Cilag Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Study: * Have active, moderate to severe, ileal and/or colonic Crohn's disease, demonstrated by: baseline CDAI score of greater than or equal to (\>=) 220 and less than equal to (\<=) 450, and endoscopy with evidence of active Crohn's disease (defined as simple endoscopic score for Crohn's disease \[SES-CD\] score \>=3 excluding the contribution of the narrowing component score) obtained within the 5 week screening period. A prior endoscopy may be used only if obtained within 3 months prior to baseline (Week 0), in which case the prior endoscopy must be centrally read again and SES-CD calculated based on this second, centralized read-out * Has had an inadequate response with, lost response to, was intolerant to, or had medical contraindications to either conventional therapy, or one previous biologic therapy approved for the treatment of Crohn's disease in the countries in which the study is conducted * Are eligible according to tuberculosis (TB) infection screening criteria * Must sign an informed consent form (ICF) or their legally acceptable representative if applicable must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. Sub-study: * Be enrolled into the main study at a participating site * Sign a separate ICF indicating that they understand the purpose of and procedures required for this sub-study and are willing to participate in the sub-study * Satisfy all inclusion criteria and none of the
Exclusion criteria
specified in the main study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Endoscopic Response at Week 48 | Week 48 | Endoscopic response defined as showing a reduction from baseline in simple endoscopic score for Crohn's disease (SES-CD) of greater than or equal to (\>=) 50 percent (%). SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. Randomized participants who stopped treatment before reaching Week 48 due to any reason, or participants without endoscopic data at Week 48 were analyzed as nonresponders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF]) | Week 48 (LOCF) | Endoscopic response defined as a reduction from baseline in SES-CD score of \>= 50%. SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments. Scores range from 0 to 60, with higher scores indicating more severe disease. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. |
| Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Clinical response defined as a \>=100-point reduction from the baseline in Crohn's Disease Activity Index (CDAI) score, or a CDAI score of \<150. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. Participants with missing data were considered as non-responder. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Clinical Remission defined as a CDAI score of \<150 points. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. Participants with missing data were considered as non-remitter. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Percentage of participants with Endoscopic remission defined as SES-CD score \<=2 at Weeks 16, 48, and Endpoint (Week 48 \[LOCF\]) were reported. SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Mucosal healing is defined as the complete absence of mucosal ulcerations in any ileocolonic segment. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study). |
| Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 [LOCF]) | Week 48 and Endpoint (Week 48 [LOCF]) | Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 \[LOCF\]) is defined as a CDAI score \<150 and not taking any corticosteroids for at least 30 days prior to Week 48 and Endpoint assessment. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. Participants with missing data were analyzed as non-remitter. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Corticosteroid-free endoscopic response defined as a reduction from baseline in SES-CD score of \>=50% and not taking any corticosteroids for at least 30 days prior to Weeks 16, 48 and endpoint (Week 48 \[LOCF\]). SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total score is sum of 4 variables. Scores range 0-60. Higher scores means severe disease. Participants with missing data were analyzed as No SES-CD Improvement. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e., first 48 weeks). |
| Change From Baseline in Serum C-reactive Protein (CRP) | Baseline, Weeks 16, 48 and Endpoint (Week 48 [LOCF] | Change from baseline in serum CRP were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Change From Baseline in Fecal Calprotectin (FC) | Baseline, Weeks 16, 48 and Endpoint (Week 48 [LOCF]) | Change from baseline in FC were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response | Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | IBDQ response was defined as \>= 16-point improvement in IBDQ total score from baseline. The IBDQ is 32-item questionnaire for participants with IBD used to evaluate disease-specific health-related quality of life. Each item score ranged from 1 (worst possible response) to 7 (best possible response). Each items were grouped into 4 domains: bowel function, emotional status, systemic symptoms and social function. The 4 domains were scored as: 10 to 70 (bowel symptoms); 5 to 35 (systemic symptoms); 12 to 84 (emotional function); 5 to 35 (social function). For each domain, higher score indicated better quality of life. Total score is sum of each item score and ranges from 32 to 224 with higher score indicating better quality of life. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e, first 48 weeks). |
| Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Percentage of participants with 7-point change from baseline in WPAI scores for each domain were reported. WPAI is 6-item (7-day recall period) well-validated questionnaire to measure impairments in work and activities that produces 4 types of domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), activity impairment. Participants who answered first question of the questionnaire 'Are you currently employed' as 'Yes' were included in absenteeism, presenteeism, and work productivity. In activity impairment all participants were included. Each score range: 0-100, higher scores=greater impairment and less productivity. LOCF: Participants who had missing value at Week 48 or stopped treatment before reaching Week 48 had last non-missing value carried forward. Endpoint: last available postbaseline result in main analysis period (first 48 weeks). |
| Percentage of Participants With Endoscopic Response at Week 48 (Premature Drop-outs Excluded) | Week 48 | Endoscopic response defined as showing a reduction from baseline in SES-CD (a validated instrument reflecting an endoscopist's global appraisal of mucosal lesions) score of \>=50%. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is calculated as sum of 4 variables for 5 bowel segments. Scores ranges 0-60. Higher scores indicates more severe disease. Randomized participants who stopped treatment before reaching Week 48 due to reasons other than lack/loss of efficacy were excluded from analysis. |
| Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | EQ-5D-5L, validated quality-of-life instrument completed by participants. It consists of EQ-5D-5L descriptive system and EQ-VAS. EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) describes participants current health state. Each dimension scores where 1 indicates no problems and 5 indicates extreme problems. EQ-5D-5L VAS records the respondent's self-rated, visual analogue scale score on a scale of 0-100, where 0 labelled as 'the worst health you can imagine and 100 labelled 'the best health you can imagine.' LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e., first 48 weeks). |
| Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | The FACIT-F scale is a 13-item fatigue scale with a 7-day recall period. It measures the level of fatigue during the usual daily activities. The level of fatigue is measured on a 4-point Likert scale (0=very much fatigue to 4=not at all fatigue). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | The HADS Score is a validated 14-item scale with 7 of the items relating to anxiety and 7 relating to depression. Each item is scored from 0 to 3, with higher scores indicating greater likelihood of depression or anxiety. Cases of anxiety or depression are each defined by subscale scores of 8 or greater and categorized as normal (score of 0 to 7), mild (score of 8 to 10), moderate (score of 11 to 14), and severe (score of 15 to 21). LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Change From Baseline in WPAI Score | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | The WPAI questionnaire is a well-validated instrument to measure impairments in work and activities. It is a 6-item questionnaire with a 7-day recall period. The WPAI questionnaire produces 4 types of scores: absenteeism (work time missed), presenteesism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Change From Baseline in Time Lost From Work | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Time lost from work was collected by asking the participants a single question, How many days did you miss from work due to your Crohn's disease in the last 4 weeks? LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Number of Participants With Adverse Events (AEs) That Occurred in Participants Administered With Ustekinumab up to Week 48 | Up to Week 48 | An adverse event is any untoward medical event that occurs in participants administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. |
| Change From Baseline in Body Weight | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Change from baseline in body weight were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Change From Baseline in Body Mass Index (BMI) | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Change from baseline in BMI were reported. BMI is a person's weight (in kilograms) divided by the square of height (in meters).LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). |
| Change From Baseline in Blood Pressure | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Change from baseline in Blood Pressure (Systolic Blood Pressure \[SPB\] and Diastolic Blood Pressure \[DBP\]) were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study). |
| Change From Baseline in Pulse Rate | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Change from baseline in pulse rate were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study). |
| Change From Baseline in IBDQ Score | Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | The IBDQ is 32-item questionnaire used to evaluate disease-specific health-related quality of life. Each item score ranged from 1 (worst possible response) to 7 (best possible response). Items were grouped into 4 domains: bowel function, emotional status, systemic symptoms and social function with scored as follows: 10 to 70 (bowel symptoms); 5 to 35 (systemic symptoms); 12 to 84 (emotional function); and 5 to 35 (social function). Higher score, better quality of life. Total score is sum of each item score and ranges from 32 to 224. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (that is, first 48 weeks of the study). Only participants with non-missing baseline value and at least one non-missing post-baseline value during main treatment period were included in analysis. |
Countries
Belgium, Czechia, Denmark, France, Germany, Italy, Netherlands, Portugal, Slovakia, Spain, Sweden, United Kingdom
Participant flow
Pre-assignment details
Out of 500 enrolled participants who received at least 1 dose of study medication, 498 participants were included in the analysis because study team decided to exclude one site due to compliance issue. Hence, number of participants who received at least one dose of study medication reduced from 500 to 498 participants.
Participants by arm
| Arm | Count |
|---|---|
| Induction Period: Ustekinumab (6 Milligrams [mg]/Kilogram [kg]) Participants were administered with approximately 6 mg/kg intravenous (IV) injection of ustekinumab at Week 0 and 90 mg subcutaneous (SC) injection of ustekinumab at Week 8. At Week 16, participants who did not achieve a Crohn's Disease Activity Index (CDAI) improvement (non-responders) of greater than or equal to (\>=) 70 points versus Week 0 (CDAI-70), left the study. Participants who achieved CDAI improvement (responders) of at least 70 points versus Week 0 were randomized in open-label maintenance period either in treat to target arm or routine care arm. | 498 |
| Total | 498 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Extension Period (Week 48- Week 104) | Adverse Event | 0 | 0 | 0 | 10 | 3 |
| Extension Period (Week 48- Week 104) | Death | 0 | 0 | 0 | 0 | 1 |
| Extension Period (Week 48- Week 104) | Did not re-consent to protocol amendment 3 | 0 | 0 | 0 | 0 | 1 |
| Extension Period (Week 48- Week 104) | Disease relapse | 0 | 0 | 0 | 0 | 3 |
| Extension Period (Week 48- Week 104) | Lack of Efficacy | 0 | 0 | 0 | 8 | 9 |
| Extension Period (Week 48- Week 104) | Lost to Follow-up | 0 | 0 | 0 | 1 | 2 |
| Extension Period (Week 48- Week 104) | Non-compliance with study drug | 0 | 0 | 0 | 1 | 0 |
| Extension Period (Week 48- Week 104) | Other | 0 | 0 | 0 | 1 | 3 |
| Extension Period (Week 48- Week 104) | Physician Decision | 0 | 0 | 0 | 0 | 2 |
| Extension Period (Week 48- Week 104) | Pregnancy | 0 | 0 | 0 | 2 | 4 |
| Extension Period (Week 48- Week 104) | Withdrawal by Subject | 0 | 0 | 0 | 5 | 9 |
| Induction Period (16 Weeks) | Adverse Event | 5 | 0 | 0 | 0 | 0 |
| Induction Period (16 Weeks) | Physician Decision | 1 | 0 | 0 | 0 | 0 |
| Induction Period (16 Weeks) | Progressive disease | 1 | 0 | 0 | 0 | 0 |
| Induction Period (16 Weeks) | Withdrawal by Subject | 3 | 0 | 0 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Adverse Event | 0 | 6 | 10 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Death | 0 | 2 | 0 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Disease relapse | 0 | 2 | 1 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Lack of Efficacy | 0 | 21 | 8 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Physician Decision | 0 | 1 | 2 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Pregnancy | 0 | 1 | 1 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Progressive disease | 0 | 0 | 1 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Received a disallowed concomitant treatment | 0 | 0 | 1 | 0 | 0 |
| Maintenance Period (Week 16-Week 48) | Withdrawal by Subject | 0 | 12 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Induction Period: Ustekinumab (6 Milligrams [mg]/Kilogram [kg]) | — |
|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 12.96 | — |
| Age, Customized 18-25 years | 112 Participants | — |
| Age, Customized 26-50 years | 302 Participants | — |
| Age, Customized 51-64 years | 71 Participants | — |
| Age, Customized >=65 years | 13 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Belgium | 29 Participants | — |
| Region of Enrollment Czech Republic | 24 Participants | — |
| Region of Enrollment Denmark | 15 Participants | — |
| Region of Enrollment France | 51 Participants | — |
| Region of Enrollment Germany | 26 Participants | — |
| Region of Enrollment Italy | 166 Participants | — |
| Region of Enrollment Netherlands | 19 Participants | — |
| Region of Enrollment Portugal | 37 Participants | — |
| Region of Enrollment Slovakia | 30 Participants | — |
| Region of Enrollment Spain | 47 Participants | — |
| Region of Enrollment Sweden | 15 Participants | — |
| Region of Enrollment United Kingdom | 39 Participants | — |
| Sex: Female, Male Female | 257 Participants | — |
| Sex: Female, Male Male | 241 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 498 | 2 / 219 | 0 / 221 | 0 / 147 | 1 / 176 |
| other Total, other adverse events | 238 / 498 | 158 / 219 | 150 / 221 | 125 / 147 | 135 / 176 |
| serious Total, serious adverse events | 28 / 498 | 26 / 219 | 29 / 221 | 21 / 147 | 23 / 176 |
Outcome results
Primary
Percentage of Participants With Endoscopic Response at Week 48
Endoscopic response defined as showing a reduction from baseline in simple endoscopic score for Crohn's disease (SES-CD) of greater than or equal to (\>=) 50 percent (%). SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. Randomized participants who stopped treatment before reaching Week 48 due to any reason, or participants without endoscopic data at Week 48 were analyzed as nonresponders.
Time frame: Week 48
Population: Full randomized analysis set (FRAS) included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Endoscopic Response at Week 48 | 37.9 Percentage of Participants | 95% Confidence Interval 31.4 |
| Maintenance Period: Routine Care | Percentage of Participants With Endoscopic Response at Week 48 | 29.9 Percentage of Participants | 95% Confidence Interval 23.9 |
p-value: =0.0871Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Blood Pressure
Change from baseline in Blood Pressure (Systolic Blood Pressure \[SPB\] and Diastolic Blood Pressure \[DBP\]) were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Blood Pressure | SBP: Change at Endpoint (Week 48 [LOCF]) | 1.9 Millimeter of mercury (mmHg) | Standard Deviation 13.21 |
| Maintenance Period: Treat to Target | Change From Baseline in Blood Pressure | SBP: Change at Week 16 | 2.3 Millimeter of mercury (mmHg) | Standard Deviation 13.16 |
| Maintenance Period: Treat to Target | Change From Baseline in Blood Pressure | DBP: Change at Week 16 | 1.1 Millimeter of mercury (mmHg) | Standard Deviation 9.46 |
| Maintenance Period: Treat to Target | Change From Baseline in Blood Pressure | SBP: Change at Week 48 | 1.9 Millimeter of mercury (mmHg) | Standard Deviation 13.21 |
| Maintenance Period: Treat to Target | Change From Baseline in Blood Pressure | DBP: Change at Week 48 | 1.2 Millimeter of mercury (mmHg) | Standard Deviation 10.02 |
| Maintenance Period: Treat to Target | Change From Baseline in Blood Pressure | DBP: Change at Endpoint (Week 48 [LOCF]) | 1.2 Millimeter of mercury (mmHg) | Standard Deviation 10.02 |
| Maintenance Period: Routine Care | Change From Baseline in Blood Pressure | DBP: Change at Week 48 | 0.6 Millimeter of mercury (mmHg) | Standard Deviation 9.85 |
| Maintenance Period: Routine Care | Change From Baseline in Blood Pressure | SBP: Change at Week 48 | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 12.47 |
| Maintenance Period: Routine Care | Change From Baseline in Blood Pressure | SBP: Change at Endpoint (Week 48 [LOCF]) | 0.5 Millimeter of mercury (mmHg) | Standard Deviation 12.47 |
| Maintenance Period: Routine Care | Change From Baseline in Blood Pressure | DBP: Change at Endpoint (Week 48 [LOCF]) | 0.6 Millimeter of mercury (mmHg) | Standard Deviation 9.85 |
| Maintenance Period: Routine Care | Change From Baseline in Blood Pressure | DBP: Change at Week 16 | 0.8 Millimeter of mercury (mmHg) | Standard Deviation 9.81 |
| Maintenance Period: Routine Care | Change From Baseline in Blood Pressure | SBP: Change at Week 16 | 0.3 Millimeter of mercury (mmHg) | Standard Deviation 12.59 |
Secondary
Change From Baseline in Body Mass Index (BMI)
Change from baseline in BMI were reported. BMI is a person's weight (in kilograms) divided by the square of height (in meters).LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Body Mass Index (BMI) | Change at Week 48 | 0.82 Kilograms per meter square (Kg/m^2) | Standard Deviation 1.622 |
| Maintenance Period: Treat to Target | Change From Baseline in Body Mass Index (BMI) | Change at Week 16 | 0.54 Kilograms per meter square (Kg/m^2) | Standard Deviation 1.052 |
| Maintenance Period: Treat to Target | Change From Baseline in Body Mass Index (BMI) | Change at Endpoint (Week 48 [LOCF]) | 0.82 Kilograms per meter square (Kg/m^2) | Standard Deviation 1.622 |
| Maintenance Period: Routine Care | Change From Baseline in Body Mass Index (BMI) | Change at Week 16 | 0.37 Kilograms per meter square (Kg/m^2) | Standard Deviation 1.236 |
| Maintenance Period: Routine Care | Change From Baseline in Body Mass Index (BMI) | Change at Week 48 | 0.46 Kilograms per meter square (Kg/m^2) | Standard Deviation 1.665 |
| Maintenance Period: Routine Care | Change From Baseline in Body Mass Index (BMI) | Change at Endpoint (Week 48 [LOCF]) | 0.46 Kilograms per meter square (Kg/m^2) | Standard Deviation 1.665 |
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Body Weight | Change at Week 48 | 2.38 Kilograms (Kg) | Standard Deviation 4.682 |
| Maintenance Period: Treat to Target | Change From Baseline in Body Weight | Change at Week 16 | 1.56 Kilograms (Kg) | Standard Deviation 2.996 |
| Maintenance Period: Treat to Target | Change From Baseline in Body Weight | Change at Endpoint (Week 48 [LOCF]) | 2.38 Kilograms (Kg) | Standard Deviation 4.682 |
| Maintenance Period: Routine Care | Change From Baseline in Body Weight | Change at Week 48 | 1.39 Kilograms (Kg) | Standard Deviation 4.877 |
| Maintenance Period: Routine Care | Change From Baseline in Body Weight | Change at Week 16 | 1.16 Kilograms (Kg) | Standard Deviation 3.586 |
| Maintenance Period: Routine Care | Change From Baseline in Body Weight | Change at Endpoint (Week 48 [LOCF]) | 1.39 Kilograms (Kg) | Standard Deviation 4.877 |
Secondary
Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score
EQ-5D-5L, validated quality-of-life instrument completed by participants. It consists of EQ-5D-5L descriptive system and EQ-VAS. EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) describes participants current health state. Each dimension scores where 1 indicates no problems and 5 indicates extreme problems. EQ-5D-5L VAS records the respondent's self-rated, visual analogue scale score on a scale of 0-100, where 0 labelled as 'the worst health you can imagine and 100 labelled 'the best health you can imagine.' LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e., first 48 weeks).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score | Change at Endpoint (Week 48 [LOCF]) | 16.5 Units on a scale | Standard Deviation 22.77 |
| Maintenance Period: Treat to Target | Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score | Change at Week 16 | 16.7 Units on a scale | Standard Deviation 20.19 |
| Maintenance Period: Treat to Target | Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score | Change at Week 48 | 16.5 Units on a scale | Standard Deviation 22.77 |
| Maintenance Period: Routine Care | Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score | Change at Week 16 | 18.7 Units on a scale | Standard Deviation 20.16 |
| Maintenance Period: Routine Care | Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score | Change at Week 48 | 16.1 Units on a scale | Standard Deviation 21.71 |
| Maintenance Period: Routine Care | Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score | Change at Endpoint (Week 48 [LOCF]) | 16.1 Units on a scale | Standard Deviation 21.71 |
Secondary
Change From Baseline in Fecal Calprotectin (FC)
Change from baseline in FC were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48 and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Fecal Calprotectin (FC) | Change at Week 16 | -988.8 Micrograms per gram (mcg/g) | Standard Deviation 3243.61 |
| Maintenance Period: Treat to Target | Change From Baseline in Fecal Calprotectin (FC) | Change at Week 48 | -1191.6 Micrograms per gram (mcg/g) | Standard Deviation 3441.64 |
| Maintenance Period: Treat to Target | Change From Baseline in Fecal Calprotectin (FC) | Change at Endpoint (Week 48 [LOCF]) | -1191.6 Micrograms per gram (mcg/g) | Standard Deviation 3441.64 |
| Maintenance Period: Routine Care | Change From Baseline in Fecal Calprotectin (FC) | Change at Week 16 | -728.2 Micrograms per gram (mcg/g) | Standard Deviation 2238.6 |
| Maintenance Period: Routine Care | Change From Baseline in Fecal Calprotectin (FC) | Change at Week 48 | -744.4 Micrograms per gram (mcg/g) | Standard Deviation 2589.3 |
| Maintenance Period: Routine Care | Change From Baseline in Fecal Calprotectin (FC) | Change at Endpoint (Week 48 [LOCF]) | -744.4 Micrograms per gram (mcg/g) | Standard Deviation 2589.3 |
Secondary
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score
The HADS Score is a validated 14-item scale with 7 of the items relating to anxiety and 7 relating to depression. Each item is scored from 0 to 3, with higher scores indicating greater likelihood of depression or anxiety. Cases of anxiety or depression are each defined by subscale scores of 8 or greater and categorized as normal (score of 0 to 7), mild (score of 8 to 10), moderate (score of 11 to 14), and severe (score of 15 to 21). LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 16: Anxiety | -2.5 Units on a scale | Standard Deviation 3.43 |
| Maintenance Period: Treat to Target | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 48: Depression | -2.4 Units on a scale | Standard Deviation 4 |
| Maintenance Period: Treat to Target | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 48: Anxiety | -2.5 Units on a scale | Standard Deviation 3.64 |
| Maintenance Period: Treat to Target | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Endpoint (Week 48 [LOCF]): Anxiety | -2.5 Units on a scale | Standard Deviation 3.64 |
| Maintenance Period: Treat to Target | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Endpoint (Week 48 [LOCF]): Depression | -2.4 Units on a scale | Standard Deviation 4 |
| Maintenance Period: Treat to Target | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 16: Depression | -2.5 Units on a scale | Standard Deviation 3.59 |
| Maintenance Period: Routine Care | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Endpoint (Week 48 [LOCF]): Depression | -2.2 Units on a scale | Standard Deviation 3.97 |
| Maintenance Period: Routine Care | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Endpoint (Week 48 [LOCF]): Anxiety | -2.7 Units on a scale | Standard Deviation 4.05 |
| Maintenance Period: Routine Care | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 16: Anxiety | -2.5 Units on a scale | Standard Deviation 3.88 |
| Maintenance Period: Routine Care | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 16: Depression | -2.4 Units on a scale | Standard Deviation 3.41 |
| Maintenance Period: Routine Care | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 48: Anxiety | -2.7 Units on a scale | Standard Deviation 4.05 |
| Maintenance Period: Routine Care | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Week 48: Depression | -2.2 Units on a scale | Standard Deviation 3.97 |
Secondary
Change From Baseline in IBDQ Score
The IBDQ is 32-item questionnaire used to evaluate disease-specific health-related quality of life. Each item score ranged from 1 (worst possible response) to 7 (best possible response). Items were grouped into 4 domains: bowel function, emotional status, systemic symptoms and social function with scored as follows: 10 to 70 (bowel symptoms); 5 to 35 (systemic symptoms); 12 to 84 (emotional function); and 5 to 35 (social function). Higher score, better quality of life. Total score is sum of each item score and ranges from 32 to 224. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (that is, first 48 weeks of the study). Only participants with non-missing baseline value and at least one non-missing post-baseline value during main treatment period were included in analysis.
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in IBDQ Score | Change at Week 16 | 41.3 Units on a scale | Standard Deviation 34.24 |
| Maintenance Period: Treat to Target | Change From Baseline in IBDQ Score | Change at Week 48 | 43.7 Units on a scale | Standard Deviation 35.16 |
| Maintenance Period: Treat to Target | Change From Baseline in IBDQ Score | Change at Endpoint (Week 48 [LOCF]) | 43.7 Units on a scale | Standard Deviation 35.16 |
| Maintenance Period: Routine Care | Change From Baseline in IBDQ Score | Change at Week 16 | 44.7 Units on a scale | Standard Deviation 33.2 |
| Maintenance Period: Routine Care | Change From Baseline in IBDQ Score | Change at Week 48 | 44.3 Units on a scale | Standard Deviation 36.94 |
| Maintenance Period: Routine Care | Change From Baseline in IBDQ Score | Change at Endpoint (Week 48 [LOCF]) | 44.3 Units on a scale | Standard Deviation 36.94 |
Secondary
Change From Baseline in Pulse Rate
Change from baseline in pulse rate were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Pulse Rate | Change at Week 16 | -1.5 Beats/minute | Standard Deviation 11.98 |
| Maintenance Period: Treat to Target | Change From Baseline in Pulse Rate | Change at Endpoint (Week 48 [LOCF]) | -0.2 Beats/minute | Standard Deviation 13.39 |
| Maintenance Period: Treat to Target | Change From Baseline in Pulse Rate | Change at Week 48 | -0.2 Beats/minute | Standard Deviation 13.39 |
| Maintenance Period: Routine Care | Change From Baseline in Pulse Rate | Change at Endpoint (Week 48 [LOCF]) | -1.7 Beats/minute | Standard Deviation 12.16 |
| Maintenance Period: Routine Care | Change From Baseline in Pulse Rate | Change at Week 16 | -2.0 Beats/minute | Standard Deviation 11.51 |
| Maintenance Period: Routine Care | Change From Baseline in Pulse Rate | Change at Week 48 | -1.7 Beats/minute | Standard Deviation 12.16 |
Secondary
Change From Baseline in Serum C-reactive Protein (CRP)
Change from baseline in serum CRP were reported. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48 and Endpoint (Week 48 [LOCF]
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Serum C-reactive Protein (CRP) | Change at Week 16 | -7.717 Milligrams per liter (mg/L) | Standard Deviation 22.0246 |
| Maintenance Period: Treat to Target | Change From Baseline in Serum C-reactive Protein (CRP) | Change at Week 48 | -7.839 Milligrams per liter (mg/L) | Standard Deviation 22.6777 |
| Maintenance Period: Treat to Target | Change From Baseline in Serum C-reactive Protein (CRP) | Change at Endpoint (Week 48 [LOCF]) | -7.839 Milligrams per liter (mg/L) | Standard Deviation 22.6777 |
| Maintenance Period: Routine Care | Change From Baseline in Serum C-reactive Protein (CRP) | Change at Week 16 | -7.345 Milligrams per liter (mg/L) | Standard Deviation 17.5658 |
| Maintenance Period: Routine Care | Change From Baseline in Serum C-reactive Protein (CRP) | Change at Week 48 | -7.909 Milligrams per liter (mg/L) | Standard Deviation 22.2139 |
| Maintenance Period: Routine Care | Change From Baseline in Serum C-reactive Protein (CRP) | Change at Endpoint (Week 48 [LOCF]) | -7.909 Milligrams per liter (mg/L) | Standard Deviation 22.2139 |
Secondary
Change From Baseline in Time Lost From Work
Time lost from work was collected by asking the participants a single question, How many days did you miss from work due to your Crohn's disease in the last 4 weeks? LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in Time Lost From Work | Change at Week 16 | -1.7 Days | Standard Deviation 4.32 |
| Maintenance Period: Treat to Target | Change From Baseline in Time Lost From Work | Change at Week 48 | -1.8 Days | Standard Deviation 4.58 |
| Maintenance Period: Treat to Target | Change From Baseline in Time Lost From Work | Change at Endpoint (Week 48 [LOCF]) | -1.8 Days | Standard Deviation 4.58 |
| Maintenance Period: Routine Care | Change From Baseline in Time Lost From Work | Change at Week 16 | -1.8 Days | Standard Deviation 6.03 |
| Maintenance Period: Routine Care | Change From Baseline in Time Lost From Work | Change at Week 48 | -2.2 Days | Standard Deviation 5.99 |
| Maintenance Period: Routine Care | Change From Baseline in Time Lost From Work | Change at Endpoint (Week 48 [LOCF]) | -2.2 Days | Standard Deviation 5.99 |
Secondary
Change From Baseline in WPAI Score
The WPAI questionnaire is a well-validated instrument to measure impairments in work and activities. It is a 6-item questionnaire with a 7-day recall period. The WPAI questionnaire produces 4 types of scores: absenteeism (work time missed), presenteesism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed for specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Absenteeism: Change at Week 16 | -12.9 Units on a scale | Standard Deviation 31.39 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Absenteeism: Change at Week 48 | -13.9 Units on a scale | Standard Deviation 34.13 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Absenteeism: Change at Endpoint (Week 48 [LOCF]) | -13.0 Units on a scale | Standard Deviation 34.87 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Presenteeism: Change at Week 16 | -23.3 Units on a scale | Standard Deviation 27.76 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Presenteeism: Change at Week 48 | -30.0 Units on a scale | Standard Deviation 31.83 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Presenteeism: Change at Endpoint (Week 48 [LOCF]) | -26.5 Units on a scale | Standard Deviation 30.5 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Work Productivity Loss: Change at Week 16 | -25.2 Units on a scale | Standard Deviation 27.71 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Work Productivity Loss: Change at Week 48 | -33.0 Units on a scale | Standard Deviation 33.98 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Work Productivity Loss: Change at Endpoint (Week 48 [LOCF]) | -29.1 Units on a scale | Standard Deviation 32.91 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Activity Impairment: Change at Week 16 | -24.1 Units on a scale | Standard Deviation 27.23 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Activity Impairment: Change at Week 48 | -29.2 Units on a scale | Standard Deviation 29.65 |
| Maintenance Period: Treat to Target | Change From Baseline in WPAI Score | Activity Impairment: Change at Endpoint (Week 48 [LOCF]) | -25.5 Units on a scale | Standard Deviation 29.13 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Activity Impairment: Change at Week 48 | -24.8 Units on a scale | Standard Deviation 28.96 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Absenteeism: Change at Week 16 | -12.5 Units on a scale | Standard Deviation 30.86 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Work Productivity Loss: Change at Week 16 | -27.2 Units on a scale | Standard Deviation 31.79 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Absenteeism: Change at Week 48 | -14.8 Units on a scale | Standard Deviation 30.22 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Activity Impairment: Change at Week 16 | -27.3 Units on a scale | Standard Deviation 26.77 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Absenteeism: Change at Endpoint (Week 48 [LOCF]) | -12.1 Units on a scale | Standard Deviation 31.92 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Work Productivity Loss: Change at Week 48 | -28.0 Units on a scale | Standard Deviation 31.66 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Presenteeism: Change at Week 16 | -26.2 Units on a scale | Standard Deviation 30.09 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Activity Impairment: Change at Endpoint (Week 48 [LOCF]) | -23.6 Units on a scale | Standard Deviation 29.08 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Presenteeism: Change at Week 48 | -26.0 Units on a scale | Standard Deviation 28.9 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Work Productivity Loss: Change at Endpoint (Week 48 [LOCF]) | -24.1 Units on a scale | Standard Deviation 33.97 |
| Maintenance Period: Routine Care | Change From Baseline in WPAI Score | Presenteeism: Change at Endpoint (Week 48 [LOCF]) | -22.5 Units on a scale | Standard Deviation 30.99 |
Secondary
Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score
The FACIT-F scale is a 13-item fatigue scale with a 7-day recall period. It measures the level of fatigue during the usual daily activities. The level of fatigue is measured on a 4-point Likert scale (0=very much fatigue to 4=not at all fatigue). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Baseline, Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maintenance Period: Treat to Target | Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score | Change at Week 16 | 9.1 Units on a scale | Standard Deviation 10.57 |
| Maintenance Period: Treat to Target | Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score | Change at Week 48 | 9.9 Units on a scale | Standard Deviation 11.35 |
| Maintenance Period: Treat to Target | Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score | Change at Endpoint (Week 48 [LOCF]) | 9.9 Units on a scale | Standard Deviation 11.35 |
| Maintenance Period: Routine Care | Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score | Change at Week 16 | 11.6 Units on a scale | Standard Deviation 10.12 |
| Maintenance Period: Routine Care | Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score | Change at Week 48 | 10.0 Units on a scale | Standard Deviation 11.11 |
| Maintenance Period: Routine Care | Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score | Change at Endpoint (Week 48 [LOCF]) | 10.0 Units on a scale | Standard Deviation 11.11 |
Secondary
Number of Participants With Adverse Events (AEs) That Occurred in Participants Administered With Ustekinumab up to Week 48
An adverse event is any untoward medical event that occurs in participants administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time frame: Up to Week 48
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance Period: Treat to Target | Number of Participants With Adverse Events (AEs) That Occurred in Participants Administered With Ustekinumab up to Week 48 | 188 Participants |
| Maintenance Period: Routine Care | Number of Participants With Adverse Events (AEs) That Occurred in Participants Administered With Ustekinumab up to Week 48 | 179 Participants |
Secondary
Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain
Percentage of participants with 7-point change from baseline in WPAI scores for each domain were reported. WPAI is 6-item (7-day recall period) well-validated questionnaire to measure impairments in work and activities that produces 4 types of domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), activity impairment. Participants who answered first question of the questionnaire 'Are you currently employed' as 'Yes' were included in absenteeism, presenteeism, and work productivity. In activity impairment all participants were included. Each score range: 0-100, higher scores=greater impairment and less productivity. LOCF: Participants who had missing value at Week 48 or stopped treatment before reaching Week 48 had last non-missing value carried forward. Endpoint: last available postbaseline result in main analysis period (first 48 weeks).
Time frame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Absenteeism | 35.0 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Work Productivity Loss | 71.4 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Presenteeism | 70.5 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Work Productivity Loss | 75.0 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Absenteeism | 34.9 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Work Productivity Loss | 72.4 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Activity Impairment | 72.1 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Presenteeism | 73.1 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Activity Impairment | 74.4 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Absenteeism | 34.9 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Activity Impairment | 67.9 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Presenteeism | 69.6 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Activity Impairment | 70.7 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Absenteeism | 39.6 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Absenteeism | 36.4 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Absenteeism | 36.3 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Presenteeism | 76.9 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Presenteeism | 72.8 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Presenteeism | 69.8 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Work Productivity Loss | 70.7 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Work Productivity Loss | 72.1 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 16: Activity Impairment | 78.3 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Week 48: Activity Impairment | 71.9 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With 7-point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain | Endpoint (Week 48 [LOCF]): Work Productivity Loss | 69.6 Percentage of Participants |
Secondary
Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Clinical Remission defined as a CDAI score of \<150 points. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. Participants with missing data were considered as non-remitter. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 16 | 72.1 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 61.6 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 77.2 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 16 | 74.2 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 69.7 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Clinical Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 78.3 Percentage of Participants |
Secondary
Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Clinical response defined as a \>=100-point reduction from the baseline in Crohn's Disease Activity Index (CDAI) score, or a CDAI score of \<150. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. Participants with missing data were considered as non-responder. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 16 | 84.5 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 68.0 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 89.5 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 16 | 89.6 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 77.8 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Clinical Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 89.6 Percentage of Participants |
Secondary
Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 [LOCF])
Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 \[LOCF\]) is defined as a CDAI score \<150 and not taking any corticosteroids for at least 30 days prior to Week 48 and Endpoint assessment. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. Participants with missing data were analyzed as non-remitter. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Week 48 and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 70.8 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 [LOCF]) | Week 48 | 56.6 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 [LOCF]) | Week 48 | 63.3 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 69.7 Percentage of Participants |
Secondary
Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Corticosteroid-free endoscopic response defined as a reduction from baseline in SES-CD score of \>=50% and not taking any corticosteroids for at least 30 days prior to Weeks 16, 48 and endpoint (Week 48 \[LOCF\]). SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total score is sum of 4 variables. Scores range 0-60. Higher scores means severe disease. Participants with missing data were analyzed as No SES-CD Improvement. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e., first 48 weeks).
Time frame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'n' (number analyzed) included participants analyzed at specified timepoints. Data was not collected for routine care arm at Week 16 as per planned analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 16 | 26.5 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 33.8 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 36.1 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 28.5 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Corticosteroid-free Endoscopic Response at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 29.4 Percentage of Participants |
Secondary
Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Percentage of participants with Endoscopic remission defined as SES-CD score \<=2 at Weeks 16, 48, and Endpoint (Week 48 \[LOCF\]) were reported. SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).
Time frame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'n' (number analyzed) refers participants analyzed at specified timepoints. Data was not collected for routine care arm at Week 16 as per planned analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 16 | 11.4 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 11.4 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 11.9 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 14.5 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Endoscopic Remission at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 15.4 Percentage of Participants |
Secondary
Percentage of Participants With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF])
Endoscopic response defined as a reduction from baseline in SES-CD score of \>= 50%. SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments. Scores range from 0 to 60, with higher scores indicating more severe disease. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward.
Time frame: Week 48 (LOCF)
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF]) | 40.2 Percentage of Participants | 95% Confidence Interval 33.6 |
| Maintenance Period: Routine Care | Percentage of Participants With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF]) | 30.8 Percentage of Participants | 95% Confidence Interval 24.8 |
Secondary
Percentage of Participants With Endoscopic Response at Week 48 (Premature Drop-outs Excluded)
Endoscopic response defined as showing a reduction from baseline in SES-CD (a validated instrument reflecting an endoscopist's global appraisal of mucosal lesions) score of \>=50%. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is calculated as sum of 4 variables for 5 bowel segments. Scores ranges 0-60. Higher scores indicates more severe disease. Randomized participants who stopped treatment before reaching Week 48 due to reasons other than lack/loss of efficacy were excluded from analysis.
Time frame: Week 48
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'N' (Number of participants analyzed) included participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Endoscopic Response at Week 48 (Premature Drop-outs Excluded) | 43.0 Percentage of Participants | 95% Confidence Interval 35.9 |
| Maintenance Period: Routine Care | Percentage of Participants With Endoscopic Response at Week 48 (Premature Drop-outs Excluded) | 32.3 Percentage of Participants | 95% Confidence Interval 25.9 |
Secondary
Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response
IBDQ response was defined as \>= 16-point improvement in IBDQ total score from baseline. The IBDQ is 32-item questionnaire for participants with IBD used to evaluate disease-specific health-related quality of life. Each item score ranged from 1 (worst possible response) to 7 (best possible response). Each items were grouped into 4 domains: bowel function, emotional status, systemic symptoms and social function. The 4 domains were scored as: 10 to 70 (bowel symptoms); 5 to 35 (systemic symptoms); 12 to 84 (emotional function); 5 to 35 (social function). For each domain, higher score indicated better quality of life. Total score is sum of each item score and ranges from 32 to 224 with higher score indicating better quality of life. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e, first 48 weeks).
Time frame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response | Week 16 | 71.7 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response | Week 48 | 58.4 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response | Endpoint (Week 48 [LOCF]) | 77.2 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response | Week 16 | 75.1 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response | Week 48 | 67.0 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response | Endpoint (Week 48 [LOCF]) | 77.8 Percentage of Participants |
Secondary
Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Mucosal healing is defined as the complete absence of mucosal ulcerations in any ileocolonic segment. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. Total SES-CD is sum of 4 variables for all 5 bowel segments. Scores range from 0-60 with higher scores indicating more severe disease. LOCF: Participants who had a missing value at Week 48 or who stopped treatment before reaching Week 48 had their last non-missing value carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study).
Time frame: Weeks 16, 48, and Endpoint (Week 48 [LOCF])
Population: FRAS included all participants who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomized. Here, 'n' (number analyzed) is defined as number of participants who were analyzed at specified timepoints. Data was not collected for routine care arm at Week 16 as per planned analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maintenance Period: Treat to Target | Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 16 | 16.0 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 14.2 Percentage of Participants |
| Maintenance Period: Treat to Target | Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 14.6 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Week 48 | 16.7 Percentage of Participants |
| Maintenance Period: Routine Care | Percentage of Participants With Mucosal Healing at Weeks 16, 48, and Endpoint (Week 48 [LOCF]) | Endpoint (Week 48 [LOCF]) | 17.6 Percentage of Participants |