Trial Outcomes & Findings for Efficacy and Safety of Two Treatment Algorithms in Adults With Moderate to Severe Crohn's Disease (NCT NCT01235689)

Last Updated: 2018-01-16

Results Overview

Percentage of participants with mucosal healing (defined as Crohn's disease endoscopy Index of severity \[CDEIS\] \< 4) and no deep ulcerations on ileocolonoscopy (defined as the absence of all deep ulcerations in all segments explored in CDEIS) at 48 weeks after randomization (48 weeks after the 1st Key visit). The ileocolonoscopies were evaluated by the site. CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. Participants with missing data 48 weeks after Randomization were counted as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

252 participants

Primary outcome timeframe

48 weeks after Randomization

Results posted on

2018-01-16

Participant Flow

This study was conducted at 59 sites in Canada, European Union, Israel, Japan, Russia, South Africa, Switzerland, Turkey, and the Ukraine. The study included a screening period, up to 8 weeks of prednisone run-in treatment, a 48-week post-randomization treatment period, and a 70 day follow-up phone call or clinic visit.

A total of 252 participants were enrolled and received study treatment, of whom * 165 entered the prednisone run-in * 157 randomized (45 prior to Week 9, 112 at Week 9) * 8 discontinued prior to randomization. * 87 randomized at Baseline. Randomization was stratified by smoking status, weight, and disease duration.

Participant milestones

Participant milestones
Measure	Clinically Driven Management Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine. Participants who randomized at Week 9 meeting success criteria started with no therapy; participants who randomized prior to Week 9 or who randomized at Week 9 but did not meet the success criteria began treatment with adalimumab. Therapy was escalated according to pre-specified failure criteria using less stringent criteria: At Key Visit 1 the criteria for management of disease activity were a CDAI decrease ≥ 70 (CR-70) compared to Baseline or CDAI \< 200 at 1 week prior to the visit. At Key Visits 3, 4, and 5 (every 12 weeks after Key visit 1), the criteria for a change in treatment were a CDAI decrease of ≥ 100 (CR-100) compared to Baseline or CDAI \< 200, and absence of prednisone during the preceding week.	Tight Control Management Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine. Participants who randomized at Week 9 meeting success criteria started with no therapy; participants who randomized prior to Week 9 or who randomized at Week 9 but did not meet the success criteria began treatment with adalimumab. Therapy was escalated according to pre-specified tight control criteria: At Key Visit 1 the success criteria were CDAI \< 150, hs-CRP, \< 5 mg/L, fecal calprotectin \< 250 μg/g, and absence of prednisone use. At Key Visits 3, 4, and 5 (every 12 weeks after Key visit 1), the criteria were CDAI \< 150, hs-CRP \< 5 mg/L, fecal calprotectin \< 250 μg/g, and absence of prednisone during the preceding week.
Overall Study STARTED	122	122
Overall Study Early Randomized (Baseline to Week 9)	63	69
Overall Study Randomized at Week 9	59	53
Overall Study COMPLETED	93	90
Overall Study NOT COMPLETED	29	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Clinically Driven Management Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine. Participants who randomized at Week 9 meeting success criteria started with no therapy; participants who randomized prior to Week 9 or who randomized at Week 9 but did not meet the success criteria began treatment with adalimumab. Therapy was escalated according to pre-specified failure criteria using less stringent criteria: At Key Visit 1 the criteria for management of disease activity were a CDAI decrease ≥ 70 (CR-70) compared to Baseline or CDAI \< 200 at 1 week prior to the visit. At Key Visits 3, 4, and 5 (every 12 weeks after Key visit 1), the criteria for a change in treatment were a CDAI decrease of ≥ 100 (CR-100) compared to Baseline or CDAI \< 200, and absence of prednisone during the preceding week.	Tight Control Management Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine. Participants who randomized at Week 9 meeting success criteria started with no therapy; participants who randomized prior to Week 9 or who randomized at Week 9 but did not meet the success criteria began treatment with adalimumab. Therapy was escalated according to pre-specified tight control criteria: At Key Visit 1 the success criteria were CDAI \< 150, hs-CRP, \< 5 mg/L, fecal calprotectin \< 250 μg/g, and absence of prednisone use. At Key Visits 3, 4, and 5 (every 12 weeks after Key visit 1), the criteria were CDAI \< 150, hs-CRP \< 5 mg/L, fecal calprotectin \< 250 μg/g, and absence of prednisone during the preceding week.
Overall Study Adverse Event	12	16
Overall Study Lack of Efficacy	12	5
Overall Study Withdrawal by Subject	3	4
Overall Study Lost to Follow-up	1	2
Overall Study Miscellaneous	1	5

Baseline Characteristics

Efficacy and Safety of Two Treatment Algorithms in Adults With Moderate to Severe Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Total n=244 Participants Total of all reporting groups
Age, Continuous	31.10 years STANDARD_DEVIATION 11.40 • n=5 Participants	32.10 years STANDARD_DEVIATION 11.97 • n=7 Participants	31.60 years STANDARD_DEVIATION 11.67 • n=5 Participants
Age, Customized < 40 years	97 Participants n=5 Participants	96 Participants n=7 Participants	193 Participants n=5 Participants
Age, Customized 40 to < 65 years	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Age, Customized ≥ 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	72 Participants n=7 Participants	141 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	50 Participants n=7 Participants	103 Participants n=5 Participants
Race/Ethnicity, Customized White	113 Participants n=5 Participants	113 Participants n=7 Participants	226 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Multi-race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Weight < 70 kg	79 Participants n=5 Participants	81 Participants n=7 Participants	160 Participants n=5 Participants
Weight ≥ 70 kg	43 Participants n=5 Participants	41 Participants n=7 Participants	84 Participants n=5 Participants
Current Tobacco Use Yes	33 Participants n=5 Participants	31 Participants n=7 Participants	64 Participants n=5 Participants
Current Tobacco Use No	89 Participants n=5 Participants	91 Participants n=7 Participants	180 Participants n=5 Participants
Disease Duration ≤ 2 years	106 Participants n=5 Participants	106 Participants n=7 Participants	212 Participants n=5 Participants
Disease Duration > 2 years	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Crohn's Disease Endoscopy Index of Severity (CDEIS)	14.26 units on a scale STANDARD_DEVIATION 6.925 • n=5 Participants	13.38 units on a scale STANDARD_DEVIATION 6.049 • n=7 Participants	13.82 units on a scale STANDARD_DEVIATION 6.503 • n=5 Participants
Crohn's Disease Activity Index (CDAI)	267.7 units on a scale STANDARD_DEVIATION 58.35 • n=5 Participants	273.3 units on a scale STANDARD_DEVIATION 59.48 • n=7 Participants	270.5 units on a scale STANDARD_DEVIATION 58.86 • n=5 Participants

PRIMARY outcome

Timeframe: 48 weeks after Randomization

Population: All randomized participants; Participants with missing CDEIS values from endoscopies performed 48 weeks after randomization were imputed as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants With Mucosal Healing and No Deep Ulcerations	30.3 percentage of participants	45.9 percentage of participants

SECONDARY outcome

Timeframe: 48 weeks after Randomization

Population: All randomized participants; non-responder imputation was used.

Deep remission was defined as CDAI \< 150, discontinuation from steroids for at least 8 weeks, absence of draining fistula, CDEIS \< 4 and no deep ulcerations. CDAI is a tool used to quantify the symptoms of patients with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon. The range of the score is from 0 to 44 where higher scores indicate more severe endoscopic activity. Participants with missing data 48 weeks after randomization were counted as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants in Deep Remission 48 Weeks After Randomization	23.0 percentage of participants	36.9 percentage of participants

SECONDARY outcome

Timeframe: 48 weeks after Randomization

Population: All randomized participants; non-responder imputation was used.

Biologic remission was defined as high sensitivity C-reactive protein (hs-CRP) \< 5 mg/L, fecal Calprotectin \< 250 μg/g, and CDEIS \< 4 at 48 weeks after randomization. CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon. The range of the score is from 0 to 44 where higher scores indicate more severe endoscopic activity. Participants with missing values 48 weeks after Randomization were counted as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants in Biologic Remission 48 Weeks After Randomization	15.6 percentage of participants	29.5 percentage of participants

SECONDARY outcome

Timeframe: 48 weeks after Randomization

Population: All randomized participants; non-responder imputation was used.

Percentage of participants with mucosal healing (defined as a CDEIS \< 4) at 48 weeks after randomization (48 weeks after the 1st Key visit). The ileocolonoscopies were evaluated by the site. CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon. The range of the score is from 0 to 44 where higher scores indicate more severe endoscopic activity. Participants with missing values 48 weeks after Randomization were counted as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants With Mucosal Healing 48 Weeks After Randomization	30.3 percentage of participants	45.9 percentage of participants

SECONDARY outcome

Timeframe: 48 weeks after Randomization

Population: All randomized participants; non-responder imputation was used.

Percentage of participants with mucosal healing (defined as CDEIS \< 4) and CDEIS \< 4 in every segment on ileocolonoscopy at 48 weeks after randomization. The ileocolonoscopies were evaluated by the site. CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon. The range of the score is from 0 to 44 where higher scores indicate more severe endoscopic activity. Participants with missing values 48 weeks after randomization were counted as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants With Mucosal Healing and CDEIS < 4 in Every Segment 48 Weeks After Randomization	23.8 percentage of participants	29.5 percentage of participants

SECONDARY outcome

Timeframe: 48 weeks after Randomization

Population: All randomized participants; non-responder imputation was used.

Complete mucosal healing was defined as CDEIS = 0. CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon. The range of the score is from 0 to 44 where higher scores indicate more severe endoscopic activity. Participants with missing values 48 weeks after randomization were counted as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants With Complete Mucosal Healing 48 Weeks After Randomization	16.4 percentage of participants	18.0 percentage of participants

SECONDARY outcome

Timeframe: 48 weeks after Randomization

Population: All randomized participants; non-responder imputation was used.

Endoscopic response was defined as a decrease CDEIS \> 5 points. CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon. The range of the score is from 0 to 44 where higher scores indicate more severe endoscopic activity. Participants with missing values 48 weeks after Randomization were counted as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants With Endoscopic Response 48 Weeks After Randomization	40.2 percentage of participants	50.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 48 weeks after Randomization

Population: Randomized participants with non-missing data at Baseline and 48 weeks after Randomization.

CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=96 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=105 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in CDEIS at 48 Weeks After Randomization	-6.4 units on a scale Standard Deviation 7.69	-7.7 units on a scale Standard Deviation 7.25

SECONDARY outcome

Timeframe: Baseline and 4 and 8 weeks during the prednisone run-in, and 2, 6, 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization.

Population: Randomized participants with non-missing data at each time point. CDAI was only measured at 14, 18, 26, 30, 38 and 42 weeks after randomization if a participant had initiated a change in treatment.

The Crohn's Disease Activity Index (CDAI) is a research tool used to quantify the symptoms of patients with Crohn's disease. Participants were asked to record the frequency of stools, abdominal pain and general well-being on a daily basis. In addition to the diary data, the investigator assessed the following for the calculation of CDAI: presence of complications (arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma gangrenosum/aphthous stomatitis, anal fissure/fistula/abscess, other fistula, and fever), the use of antidiarrheal medicines, presence of an abdominal mass, hematocrit, and body weight. The CDAI is the sum of the products of each item multiplied by a weighting factor and generally ranges from 0 up to 600, where remission of Crohn's disease is defined as CDAI \< 150, and severe disease is defined as CDAI \> 450. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in CDAI Over Time 2 Weeks After Randomization	-80.2 units on a scale Standard Deviation 82.27	-110.1 units on a scale Standard Deviation 85.06
Change From Baseline in CDAI Over Time Week 4 of Prednisone Run-in	-78.3 units on a scale Standard Deviation 80.02	-90.9 units on a scale Standard Deviation 81.53
Change From Baseline in CDAI Over Time Week 8 of Prednisone Run-in	-64.2 units on a scale Standard Deviation 90.48	-105.5 units on a scale Standard Deviation 88.40
Change From Baseline in CDAI Over Time 6 Weeks After Randomization	-93.1 units on a scale Standard Deviation 100.81	-130.8 units on a scale Standard Deviation 89.40
Change From Baseline in CDAI Over Time 11 Weeks After Randomization	-103.5 units on a scale Standard Deviation 98.65	-141.0 units on a scale Standard Deviation 97.82
Change From Baseline in CDAI Over Time 14 Weeks After Randomization	-71.1 units on a scale Standard Deviation 89.18	-101.2 units on a scale Standard Deviation 115.90
Change From Baseline in CDAI Over Time 18 Weeks After Randomization	-69.9 units on a scale Standard Deviation 78.95	-112.0 units on a scale Standard Deviation 115.01
Change From Baseline in CDAI Over Time 23 Weeks After Randomization	-143.3 units on a scale Standard Deviation 97.83	-154.1 units on a scale Standard Deviation 101.63
Change From Baseline in CDAI Over Time 26 Weeks After Randomization	-71.8 units on a scale Standard Deviation 129.09	-135.7 units on a scale Standard Deviation 112.43
Change From Baseline in CDAI Over Time 30 Weeks After Randomization	-47.9 units on a scale Standard Deviation 143.75	-143.8 units on a scale Standard Deviation 103.54
Change From Baseline in CDAI Over Time 35 Weeks After Randomization	-140.4 units on a scale Standard Deviation 104.83	-166.4 units on a scale Standard Deviation 93.12
Change From Baseline in CDAI Over Time 38 Weeks After Randomization	-60.8 units on a scale Standard Deviation 83.51	-132.8 units on a scale Standard Deviation 103.15
Change From Baseline in CDAI Over Time 42 Weeks After Randomization	-76.8 units on a scale Standard Deviation 78.53	-107.4 units on a scale Standard Deviation 99.19
Change From Baseline in CDAI Over Time 48 Weeks After Randomization	-146.2 units on a scale Standard Deviation 102.87	-175.8 units on a scale Standard Deviation 97.69

SECONDARY outcome

Timeframe: From Randomization to 48 weeks after Randomization

Population: Randomized participants

Time to Crohn's disease flare, where flare is defined as an increase in CDAI ≥ 70 points compared to Week 8 or Early Randomization CDAI, and a CDAI \> 220.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Time to Crohn's Disease Flare	NA days Could not be estimated due to the low number of flare events	NA days Could not be estimated due to the low number of flare events

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: Randomized participants

Clinical remission was defined as CDAI \< 150. CDAI is a tool used to quantify the symptoms of patients with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI scores generally range from 0 to 600 where higher scores indicate more severe disease.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Time to Clinical Remission	78 days Interval 28.0 to 163.0	43 days Interval 15.0 to 101.0

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: Randomized participants

Steroid-free remission was defined as CDAI \< 150 and discontinuation from steroids for at least 8 weeks. CDAI is a tool used to quantify the symptoms of patients with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Time to Steroid-free Remission	162 days Interval 80.0 to 255.0	159 days Interval 78.0 to 168.0

SECONDARY outcome

Timeframe: Baseline and 4 and 8 weeks during the prednisone run-in, and 2, 6, 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization.

Population: Randomized participants; non-responder imputation was used. CDAI was only measured at 14, 18, 26, 30, 38 and 42 weeks after randomization if a participant had initiated a change in treatment.

Clinical remission was defined as CDAI \< 150. CDAI is a tool used to quantify the symptoms of patients with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. Participants with missing data at each time point were counted as non-responders.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants in Clinical Remission Over Time Week 4 of Prednisone Run-in	24.6 percentage of participants	30.3 percentage of participants
Percentage of Participants in Clinical Remission Over Time Week 8 of Prednisone Run-in	14.8 percentage of participants	22.1 percentage of participants
Percentage of Participants in Clinical Remission Over Time 2 Weeks After Randomization	23.8 percentage of participants	41.0 percentage of participants
Percentage of Participants in Clinical Remission Over Time 6 Weeks After Randomization	32.8 percentage of participants	47.5 percentage of participants
Percentage of Participants in Clinical Remission Over Time 11 Weeks After Randomization	41.8 percentage of participants	62.3 percentage of participants
Percentage of Participants in Clinical Remission Over Time 14 Weeks After Randomization	8.2 percentage of participants	6.6 percentage of participants
Percentage of Participants in Clinical Remission Over Time 18 Weeks After Randomization	9.0 percentage of participants	8.2 percentage of participants
Percentage of Participants in Clinical Remission Over Time 23 Weeks After Randomization	50.8 percentage of participants	65.6 percentage of participants
Percentage of Participants in Clinical Remission Over Time 26 Weeks After Randomization	4.1 percentage of participants	20.5 percentage of participants
Percentage of Participants in Clinical Remission Over Time 30 Weeks After Randomization	3.3 percentage of participants	23.0 percentage of participants
Percentage of Participants in Clinical Remission Over Time 35 Weeks After Randomization	45.1 percentage of participants	59.8 percentage of participants
Percentage of Participants in Clinical Remission Over Time 38 Weeks After Randomization	4.1 percentage of participants	9.0 percentage of participants
Percentage of Participants in Clinical Remission Over Time 42 Weeks After Randomization	4.1 percentage of participants	7.4 percentage of participants
Percentage of Participants in Clinical Remission Over Time 48 Weeks After Randomization	43.4 percentage of participants	59.8 percentage of participants

SECONDARY outcome

Timeframe: 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Percentage of Participants in Steroid-free Remission Over Time 11 Weeks After Randomization	23.8 percentage of participants	39.3 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 14 Weeks After Randomization	4.1 percentage of participants	4.9 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 18 Weeks After Randomization	3.3 percentage of participants	7.4 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 23 Weeks After Randomization	45.1 percentage of participants	63.1 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 26 Weeks After Randomization	2.5 percentage of participants	18.9 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 30 Weeks After Randomization	0.8 percentage of participants	21.3 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 35 Weeks After Randomization	42.6 percentage of participants	59.0 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 38 Weeks After Randomization	4.1 percentage of participants	9.0 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 42 Weeks After Randomization	4.1 percentage of participants	7.4 percentage of participants
Percentage of Participants in Steroid-free Remission Over Time 48 Weeks After Randomization	39.3 percentage of participants	59.8 percentage of participants

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: Randomized participants

Hospitalization was defined as a visit to hospital/clinic resulting in admission and overnight stay in hospital/clinic.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Time to All-cause Hospitalization	NA days Could not be estimated due to the low number of hospitalization events	NA days Could not be estimated due to the low number of hospitalization events

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: Randomized participants

Crohn's disease-related hospitalization was defined as a visit to hospital/clinic resulting in admission and overnight stay in hospital/clinic for reasons related to Crohn's disease (CD). Hospitalization for adverse events relating to study medication, i.e., prednisone, azathioprine or adalimumab, were according to Investigator's clinical judgment.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Time to Crohn's Disease-related Hospitalization or Hospitalization Due to Adverse Event Relating to Study Medication	NA days Could not be estimated due to the low number of hospitalization events	NA days Could not be estimated due to the low number of hospitalization events

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: All randomized participants

Major Crohn's disease-related intra-abdominal surgery included: * bowel resection * ostomy * by-pass * strictureplasty * drainage of abdominal or pelvic abscess (surgical drainage or percutaneous drainage by interventional radiology). The following were excluded: * debridement * exploration laparotomy * abdominal surgery for other reason * perineal related surgery * abscess drainage * placement of setons * fistulotomy * Total parental nutrition (TPN) use

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Number of Major Crohn's Disease-related Surgeries After Randomization	3 surgeries	6 surgeries

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: All randomized participants

Any hospitalization with an overnight stay in hospital/clinic related to Crohn's disease.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Number of Crohn's Disease-related Hospitalizations After Randomization	29 hospitalizations	14 hospitalizations

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: All randomized participants

Hospitalization was defined as a visit to hospital/clinic resulting in admission and overnight stay in hospital/clinic.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Number of All-cause Hospitalizations After Randomization	37 hospitalizations	25 hospitalizations

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: Randomized participants with all-cause hospitalizations

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=26 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=22 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Total Length of Stay in Hospital for All-cause Hospitalizations	40.2 days Standard Deviation 45.72	50.1 days Standard Deviation 85.69

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: Randomized participants with Crohn's disease-related hospitalizations

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=21 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=13 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Total Length of Stay in Hospital for Crohn's Disease-related Hospitalizations	9.8 days Standard Deviation 7.21	15.8 days Standard Deviation 20.39

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: All randomized participants

The total number of CD-related surgical procedures included major CD-related surgery, debridement, perineal related surgery - abscess drainage, seton placement, fistulotomy, and TPN.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Number of Crohn's Disease-related Surgical Procedures After Randomization	9 surgical procedures	7 surgical procedures

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: Randomized participants

Hospitalization was defined as a visit to hospital/clinic resulting in admission and overnight stay in hospital/clinic. Hospitalization due to emergency was defined as a hospitalization admitted through the emergency department.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Time to Crohn's Disease-related Hospitalization Due to Emergency	NA days Could not be estimated due to the low number of emergency hospitalizations	NA days Could not be estimated due to the low number of emergency hospitalizations

SECONDARY outcome

Timeframe: From Randomization through 48 weeks after Randomization

Population: All randomized participants

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Number of Crohn's Disease-related Hospitalizations Due to Emergency	11 emergency hospitalizations	4 emergency hospitalizations

SECONDARY outcome

Timeframe: From Baseline to 48 weeks after Randomization

Population: All randomized participants; non-responder imputation was used.

Participants' Crohn's Disease was classified according to the Montreal Classification which classifies CD according to its predominant phenotypic elements (age at diagnosis, location, and disease behavior) based on the results of clinical examination and endoscopy. Disease behavior was classified according to the following: B1 = non-stricturing, non-penetrating; B2 = structuring; B3 = penetrating; P = perianal disease modifier. The change in Montreal Classification is presented in three categories: no change, deterioration, and improvement. Deterioration was defined as an increase in behavior index between 1 and 3, or development of perianal disease. Participants with missing data at Week 48 were classified as deterioration.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change in Crohn's Disease Behavior According to Montreal Classification Deterioration	54 Participants	35 Participants
Change in Crohn's Disease Behavior According to Montreal Classification No Change	64 Participants	79 Participants
Change in Crohn's Disease Behavior According to Montreal Classification Improvement	4 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline and 8 weeks during the prednisone run-in, and 11, 23, 35, and 48 weeks after Randomization.

Population: Randomized participants; last observation carried forward imputation was used.

High sensitivity C-reactive protein was analyzed by a central laboratory.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Over Time Week 8 of Prednisone Run-in	-10.3 mg/L Standard Deviation 40.04	-9.2 mg/L Standard Deviation 33.67
Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Over Time 11 Weeks After Randomization	-14.6 mg/L Standard Deviation 31.87	-15.9 mg/L Standard Deviation 26.38
Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Over Time 23 Weeks After Randomization	-15.1 mg/L Standard Deviation 31.59	-14.7 mg/L Standard Deviation 28.94
Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Over Time 35 Weeks After Randomization	-11.0 mg/L Standard Deviation 31.22	-14.0 mg/L Standard Deviation 28.85
Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Over Time 48 Weeks After Randomization	-12.3 mg/L Standard Deviation 28.97	-13.2 mg/L Standard Deviation 28.93

SECONDARY outcome

Timeframe: Baseline and 48 weeks after Randomization

Population: Randomized participants with Baseline data; non-responder imputation was used.

Stool samples were analyzed by a central laboratory for fecal calprotectin qualitative measurement (\< 250 or ≥ 250 μg/g). Results are reported for participants in each category at Baseline and 48 weeks after Randomization. Participants with missing data 48 weeks after Randomization were counted as having fecal calprotectin ≥ 250µg/g.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=122 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=120 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change in Fecal Calprotectin From Baseline to 48 Weeks After Randomization Baseline ≥ 250µg/g and Week 48 ≥ 250µg/g	68 Participants	52 Participants
Change in Fecal Calprotectin From Baseline to 48 Weeks After Randomization Baseline < 250µg/g and Week 48 < 250µg/g	8 Participants	14 Participants
Change in Fecal Calprotectin From Baseline to 48 Weeks After Randomization Baseline < 250µg/g and Week 48 ≥ 250µg/g	9 Participants	10 Participants
Change in Fecal Calprotectin From Baseline to 48 Weeks After Randomization Baseline ≥ 250µg/g and Week 48 < 250µg/g	37 Participants	44 Participants

SECONDARY outcome

Timeframe: From Baseline through 48 weeks after Randomization

Population: Participants who received prednisone

The total dose of prednisone each participant received during both the run-in phase and post-randomization treatment phase.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=102 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=104 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Total Dose of Prednisone	1505.7 mg Standard Deviation 1029.83	1369.8 mg Standard Deviation 1137.65

SECONDARY outcome

Timeframe: Baseline and 48 weeks after Randomization

Population: Randomized participants with baseline and at least one post-baseline value; last observation carried forward imputation was used.

The IBDQ measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease, feeling in general, and mood. Each question is answered on a scale from 1 (all of the time) to 7 ( none of the time); the total score ranges from 7 (worst) to 224 (best). A positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=111 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=111 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in Quality of Life in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score	31.2 units on a scale Standard Deviation 39.33	41.9 units on a scale Standard Deviation 36.90

SECONDARY outcome

Timeframe: Baseline and 48 weeks after Randomization

Population: Randomized participants with baseline and at least one post-baseline value; last observation carried forward imputation was used. The first 3 scores were only calculated for participants who were employed.

The WPAI:CD questionnaire was used to assess impairments in both paid work and unpaid work due to symptoms of Crohn's Disease. The self-administered questionnaire consisted of 6 questions. Work time missed was defined as the percentage of time absent from work due to Crohn's disease in the past week. Impairment while working is the participant's assessment of the degree to which Crohn's disease affected productivity while working in the past 7 days. Total work productivity impairment takes into account both hours missed due to Crohn's disease symptoms and the patient's assessment of the degree to which Crohn's disease affected their productivity while working. Total activity impairment is the percent impairment of non-work related activities due to Crohn's disease. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=119 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=118 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in Work Productivity Activity Index - Crohn's Disease (WPAI:CD) Work time missed	-12.8 percent impairment Standard Deviation 30.17	-17.6 percent impairment Standard Deviation 41.33
Change From Baseline in Work Productivity Activity Index - Crohn's Disease (WPAI:CD) Impairment while working	-17.5 percent impairment Standard Deviation 23.37	-25.8 percent impairment Standard Deviation 34.32
Change From Baseline in Work Productivity Activity Index - Crohn's Disease (WPAI:CD) Overall work impairment	-21.7 percent impairment Standard Deviation 29.68	-29.2 percent impairment Standard Deviation 39.53
Change From Baseline in Work Productivity Activity Index - Crohn's Disease (WPAI:CD) Activity impairment	-19.2 percent impairment Standard Deviation 27.16	-27.7 percent impairment Standard Deviation 33.22

SECONDARY outcome

Timeframe: Baseline and 48 weeks after Randomization

Population: Randomized participants with Baseline and at least one post-baseline value; last observation carried forward imputation was used.

The PHQ-9 is a 9-item questionnaire for assessing the severity of depression. Each question is answered on a scale from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 27, where higher scores indicate more severe depression. A negative change from Baseline score indicates improvement.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=120 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=120 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in Patient Health Questionnaire - 9 (PHQ9)	-3.6 units on a scale Standard Deviation 5.65	-5.6 units on a scale Standard Deviation 5.95

SECONDARY outcome

Timeframe: Baseline and 48 weeks after Randomization

Population: Randomized participants with Baseline and at least 1 post-baseline value; last observation carried forward imputation was used

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, from 0 (not at all) to 4 (very much). The FACIT-Fatigue score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement. .

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=120 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=119 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score	7.6 units on a scale Standard Deviation 10.85	13.0 units on a scale Standard Deviation 13.19

SECONDARY outcome

Timeframe: Baseline and 48 weeks after Randomization

Population: Randomized participants with Baseline and at least one post-baseline value; last observation carried forward imputation was used.

The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2 is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary (PCS) score summarizes the subscales physical functioning, role-physical, bodily pain, and general health. The mental component summary (MCS) score summarizes the subscales vitality, social functioning, role-emotional, and mental health. Each score ranges from 0 to 100 where higher scores indicate a better quality of life. A positive change from Baseline score indicates an improvement.

Outcome measures

Outcome measures
Measure	Clinically Driven Management n=119 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=118 Participants Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Change From Baseline in Short-Form 36 (SF-36) Physical Component Summary and Mental Component Summary Scores Physical Component Summary Score	6.3 units on a scale Standard Deviation 8.34	9.2 units on a scale Standard Deviation 10.22
Change From Baseline in Short-Form 36 (SF-36) Physical Component Summary and Mental Component Summary Scores Mental Component Summary Score	5.8 units on a scale Standard Deviation 12.24	9.3 units on a scale Standard Deviation 12.40

Adverse Events

Clinically Driven Management

Serious events: 25 serious events

Other events: 78 other events

Deaths: 0 deaths

Tight Control Management

Serious events: 22 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Medical Services

AbbVie (prior sponsor Abbott)

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Clinically Driven Management n=122 participants at risk Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.	Tight Control Management n=122 participants at risk Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use. Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.
Blood and lymphatic system disorders ANAEMIA	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	6.6% 8/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Gastrointestinal disorders ABDOMINAL PAIN	12.3% 15/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	10.7% 13/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	3.3% 4/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	6.6% 8/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Gastrointestinal disorders CROHN'S DISEASE	18.9% 23/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	9.0% 11/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Gastrointestinal disorders DIARRHOEA	1.6% 2/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	8.2% 10/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Gastrointestinal disorders NAUSEA	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	17.2% 21/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Gastrointestinal disorders VOMITING	3.3% 4/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	10.7% 13/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
General disorders FATIGUE	9.0% 11/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	9.0% 11/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
General disorders INJECTION SITE ERYTHEMA	0.00% 0/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	6.6% 8/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
General disorders PYREXIA	9.8% 12/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	7.4% 9/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Infections and infestations INFLUENZA	6.6% 8/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Infections and infestations NASOPHARYNGITIS	14.8% 18/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	14.8% 18/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Infections and infestations TONSILLITIS	0.82% 1/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders ARTHRALGIA	15.6% 19/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	13.9% 17/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Nervous system disorders DIZZINESS	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Nervous system disorders HEADACHE	12.3% 15/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	14.8% 18/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders COUGH	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	5.7% 7/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	8.2% 10/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	3.3% 4/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Skin and subcutaneous tissue disorders ALOPECIA	6.6% 8/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	4.1% 5/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.
Skin and subcutaneous tissue disorders RASH	7.4% 9/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.	3.3% 4/122 • Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from randomization until 70 days after the last dose of study drug (up to 58 weeks). TEAEs and TESAEs are defined as any adverse event or serious adverse event that begins or worsens in severity on or after randomization until 70 days after the last dose of study drug.