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Clinical Trial Results:
Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn’s Disease Patients Treated with Ustekinumab

Summary
EudraCT number	2016-002918-43
Trial protocol	GB SE ES BE DE NL FR PT SK DK IT
Global end of trial date	20 Jul 2021

Results information
Results version number	v1(current)
This version publication date	30 Jul 2022
First version publication date	30 Jul 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CNTO1275CRD3005

ISRCTN number

US NCT number

NCT03107793

WHO universal trial number (UTN)

Sponsor organisation name

Janssen-Cilag International N.V.

Sponsor organisation address

Turnhoutseweg 30, Beerse, Belgium, B-2340

Public contact

Clinical Registry Group, Janssen-Cilag International N.V., ClinicalTrialsEU@its.jnj.com

Scientific contact

Clinical Registry Group, Janssen-Cilag International N.V., ClinicalTrialsEU@its.jnj.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

20 Jul 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Jul 2021

Was the trial ended prematurely?

Main objective of the trial

The main objective of the study was to evaluate the efficacy of a Treat to Target (T2T) strategy coupled with early endoscopic assessment versus a clinically driven (routine care [RC]) approach in achieving endoscopic response.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Apr 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 29

Country: Number of subjects enrolled

Czechia: 24

Country: Number of subjects enrolled

Denmark: 15

Country: Number of subjects enrolled

France: 51

Country: Number of subjects enrolled

Germany: 26

Country: Number of subjects enrolled

Italy: 166

Country: Number of subjects enrolled

Netherlands: 19

Country: Number of subjects enrolled

Portugal: 37

Country: Number of subjects enrolled

Slovakia: 30

Country: Number of subjects enrolled

Spain: 47

Country: Number of subjects enrolled

Sweden: 15

Country: Number of subjects enrolled

United Kingdom: 39

Worldwide total number of subjects

498

EEA total number of subjects

459

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

485

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Out of 500 enrolled subjects who received at least 1 dose of study medication, 498 subjects were included in the analysis because study team decided to exclude one site due to compliance issue. Hence, number of subjects who received at least one dose of study medication reduced from 500 to 498 subjects.

Period 1 title

Induction Period (16 Weeks)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Induction Period: Ustekinumab (6 Milligrams [mg]/Kilogram[kg])

Arm description

Subjects 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, subjects 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. Subjects who achieved CDAI improvement (responders) of at least 70 points versus Week 0 were randomised in open-label maintenance period either with treat to target arm or routine care arm.

Arm type

Experimental

Investigational medicinal product name

Ustekinumab 90 mg

Investigational medicinal product code

Other name

STELARA

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Ustekinumab 90 mg was administered through SC injection at Week 8.

Investigational medicinal product name

Ustekinumab 6 mg/kg

Investigational medicinal product code

Other name

STELARA

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Ustekinumab 6 mg/kg was administered through IV injection at Week 0.

Number of subjects in period 1	Induction Period: Ustekinumab (6 Milligrams [mg]/Kilogram[kg])
Started	498
Completed	488
Not completed	10
Consent withdrawn by subject	3
Physician decision	1
Adverse event	5
Progressive disease	1

Period 2 title

Maintenance Period (Week 16-Week 48)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Treat to Target

Arm description

Subjects with less than (<) 25 percent (%) improvement in simple endoscopic score for Crohn’s disease (SES-CD) at Week 16 versus baseline received ustekinumab 90 mg SC dose 8-weekly maintenance treatment while subjects with >= 25% improvement in SES-CD score at Week 16 versus baseline received ustekinumab 90 mg SC dose 12-weekly treatment based on centrally-read ileocolonoscopy findings. From Week 24 for subjects assigned to the 8-weekly regimen or from Week 20 for the 12-weekly regimen group ustekinumab 90 mg SC maintenance treatment was directed by treat to target assessments based on C-reactive protein (CRP) and CDAI assessments. Subjects previously on 12-weekly regimens were adjusted to 8-weekly dosing; those previously on 8-weekly regimens were adjusted to 4-weekly dosing. Subjects subsequently failing to meet treatment targets at the next assessment visit 4 weeks after dosing were not able to optimize dosing further and left the study.

Arm type

Experimental

Investigational medicinal product name

Ustekinumab 90 mg

Investigational medicinal product code

Other name

STELARA

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Ustekinumab 90 mg was administered through SC injection.

Routine Care

Arm description

Subjects received ustekinumab 90 mg SC dose every 8-weeks or every 12-weeks according to clinical judgment. At Week 16, (that is, 8 weeks after the first SC dose), subjects who did not show adequate response based on the investigator’s judgment received a second ustekinumab 90 mg SC dose at that time. Clinical assessments in case of disease flare were performed at investigator’s discretion. Subjects who lost response during 12-weekly could adjust the dosing to 8-weekly maintenance treatment. Subjects previously received 8-weekly ustekinumab treatment were unable to adjust the dose following disease flare and left the study as per investigator’s judgment.

Arm type

Active comparator

Investigational medicinal product name

Ustekinumab 90 mg

Investigational medicinal product code

Other name

STELARA

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Ustekinumab 90 mg was administered through SC injection.

Number of subjects in period 2 ^[1]	Treat to Target	Routine Care
Started	219	221
Completed	173	193
Not completed	46	28
Consent withdrawn by subject	12	4
Physician decision	1	2
Received a disallowed concomitant treatment	-	1
Death	2	-
Disease relapse	2	1
Pregnancy	1	1
Adverse event	6	10
Lost to follow-up	1	-
Progressive disease	-	1
Lack of efficacy	21	8

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Out of 488 subjects who completed the induction period, 48 subjects were not randomized in Maintenance period due to reasons such as, non CDAI-70 responders at Week 16, lack of Efficacy, adverse events, pregnancy, withdrawal by subjects, etc.

Period 3 title

Extension Period (Week 48-Week 104)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Treat to Target

Arm description

From Week 48, subjects continued to receive SC ustekinumab 90 mg in the long-term extension (LTE) period up to Week 104. The frequency of ustekinumab dosing with escalation/de-escalation between once in 12 weeks (q12w)/q8w/q4w was based on the following targets: endoscopic remission (CD [SES-CD] score less than or equal to [<=] 2) and corticosteroid (CS)-free clinical remission (CDAI score of <150 points of >=16 weeks duration) at Week 48; and later, on CS-free clinical remission and biomarker remission (C-reactive protein <=10 miligrams per liter [mg/L] and fecal calprotectin <=250 micrograms per gram [mcg/g]) at 2 consecutive visits 8 weeks apart. Subjects on q4w dosing failing to reach targets were discontinued.

Arm type

Experimental

Investigational medicinal product name

Ustekinumab 90 mg

Investigational medicinal product code

Other name

STELARA

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Ustekinumab 90 mg was administered through SC injection.

Routine Care

Arm description

From Week 48, subjects continued to receive SC ustekinumab 90 mg in the long-term extension (LTE) period up to Week 104. The frequency of ustekinumab dosing with escalation/de-escalation between once in 12 weeks (q12w)/q8w/q4w was based on the following targets: endoscopic remission (CD [SES-CD] score <=2) and corticosteroid (CS)-free clinical remission (CDAI score of <150 points of >=16 weeks duration) at Week 48; and later, on CS-free clinical remission and biomarker remission (C-reactive protein <=10 mg/L and fecal calprotectin <=250 mcg/g) at 2 consecutive visits 8 weeks apart. Subjects on q4w dosing failing to reach targets were discontinued.

Arm type

Active comparator

Investigational medicinal product name

Ustekinumab 90 mg

Investigational medicinal product code

Other name

STELARA

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Ustekinumab 90 mg was administered through SC injection.

Number of subjects in period 3 ^[2]	Treat to Target	Routine Care
Started	147	176
Completed	119	139
Not completed	28	37
Consent withdrawn by subject	5	9
Physician decision	-	2
Did not re-consent to protocol amendment 3	-	1
Death	-	1
Pregnancy	2	4
Disease relapse	-	3
Adverse event	10	3
Non-compliance with study drug	1	-
Unspecified	1	3
Lost to follow-up	1	2
Lack of efficacy	8	9

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Out of 366 subjects who completed the maintenance period, 43 subjects were not randomized in Extension period.

Baseline characteristics

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Reporting group title

Induction Period: Ustekinumab (6 Milligrams [mg]/Kilogram[kg])

Reporting group description

Reporting group values	Induction Period: Ustekinumab (6 Milligrams [mg]/Kilogram[kg])	Total
Number of subjects	498	498
Title for AgeCategorical
Units: subjects
children	0	0
adolescents	0	0
adults	485	485
elderly 65 to 84	13	13
elderly over 85	0	0
Title for AgeContinuous
Units: years
arithmetic mean (standard deviation)	37 ( 12.96 )	-
Title for Gender
Units: subjects
Female	257	257
Male	241	241

End points

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Reporting group title

Induction Period: Ustekinumab (6 Milligrams [mg]/Kilogram[kg])

Reporting group description

Reporting group title

Treat to Target

Reporting group description

Reporting group title

Routine Care

Reporting group description

Reporting group title

Treat to Target

Reporting group description

Reporting group title

Routine Care

Reporting group description

From Week 48, subjects continued to receive SC ustekinumab 90 mg in the long-term extension (LTE) period up to Week 104. The frequency of ustekinumab dosing with escalation/de-escalation between once in 12 weeks (q12w)/q8w/q4w was based on the following targets: endoscopic remission (CD [SES-CD] score <=2) and corticosteroid (CS)-free clinical remission (CDAI score of <150 points of >=16 weeks duration) at Week 48; and later, on CS-free clinical remission and biomarker remission (C-reactive protein <=10 mg/L and fecal calprotectin <=250 mcg/g) at 2 consecutive visits 8 weeks apart. Subjects on q4w dosing failing to reach targets were discontinued.

Primary: Percentage of Subjects With Endoscopic Response at Week 48

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End point title

Percentage of Subjects With Endoscopic Response at Week 48

End point description

Endoscopic response defined as showing a reduction from baseline in simple endoscopic score for Crohn's disease (SES-CD) 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. 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. Randomised subjects who stopped treatment before reaching Week 48 due to any reason, or subjects without endoscopic data at Week 48 were considered as nonresponders. Full randomised analysis set (FRAS) included all subjects who received at least 1 dose of study agent and were randomised at Week 16, regardless of study treatment being administered once randomised.

End point type

Primary

End point timeframe

Week 48

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)	37.9 (31.4 to 44.7)	29.9 (23.9 to 36.4)

Statistical Analysis 1

Comparison groups

Treat to Target v Routine Care

Number of subjects included in analysis

440

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0871

Method

Cochran-Mantel-Haenszel

Confidence interval

Secondary: Percentage of Subjects With Endoscopic Response at Week 48 (Premature Drop-outs Excluded)

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End point title

Percentage of Subjects With Endoscopic Response at Week 48 (Premature Drop-outs Excluded)

End point description

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. Randomised subjects who stopped treatment before reaching Week 48 due to reasons other than lack/loss of efficacy were excluded from analysis. FRAS included all subjects who received at least 1 dose of study agent and were randomised at Week 16, regardless of study treatment being administered once randomised. Here, 'N' (Number analysed) included subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 48

End point values	Treat to Target	Routine Care
Number of subjects analysed	193	198
Units: Percentage of Subjects
number (confidence interval 95%)	43.0 (35.9 to 50.3)	32.3 (25.9 to 39.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF])

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End point title

Percentage of Subjects With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF])

End point description

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. Last observation carried forward: subjects who had a missing SES-CD score at Week 48 or who stopped treatment before reaching Week 48 had their last SES-CD score carried forward. FRAS included subjects who received at least 1 dose of study agent and were randomised at Week 16, regardless of study treatment being administered once randomised.

End point type

Secondary

End point timeframe

Week 48

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)	40.2 (33.6 to 47.0)	30.8 (24.8 to 37.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Clinical Response at Weeks 16, 48, and Endpoint (LOCF)

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End point title

Percentage of Subjects With Clinical Response at Weeks 16, 48, and Endpoint (LOCF)

End point description

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 subjects 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. Subjects with missing data were analyzed as non-responder. FRAS included all subjects who received at least 1 dose of study agent and were randomised at Week 16, regardless of study treatment being administered once randomised. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).

End point type

Secondary

End point timeframe

Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)
Week 16	85.4 (80.0 to 89.8)	89.6 (84.8 to 93.3)
Week 48	68.0 (61.4 to 74.2)	77.8 (71.8 to 83.1)
Endpoint (LOCF)	89.5 (84.7 to 93.2)	89.6 (84.8 to 93.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Clinical Remission at Weeks 16, 48, and Endpoint (LOCF)

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End point title

Percentage of Subjects With Clinical Remission at Weeks 16, 48, and Endpoint (LOCF)

End point description

Clinical Remission defined as a CDAI score of <150 points. The CDAI score is used to quantify the symptoms of subjects 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. Subjects with missing data were analysed as non-remitter. FRAS included all subjects who received at least 1 dose of study agent and were randomised at Week 16, regardless of study treatment being administered once randomised. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study).

End point type

Secondary

End point timeframe

Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)
Week 16	72.1 (65.7 to 78.0)	74.2 (67.9 to 79.8)
Week 48	61.6 (54.9 to 68.1)	69.7 (63.2 to 75.7)
Endpoint (LOCF)	77.2 (71.0 to 82.6)	78.3 (72.3 to 83.5)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Endoscopic Remission at Weeks 16, 48, and Endpoint (LOCF)

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End point title

Percentage of Subjects With Endoscopic Remission at Weeks 16, 48, and Endpoint (LOCF)

End point description

Endoscopic remission defined as SES-CD <=2. SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. It 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. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e, first 48 weeks). FRAS was used. Here, 'n' (number analysed) refers subjects analysed at specified timepoints. '99999' refers to data not collected for routine care arm at Week 16 as per planned analysis.

End point type

Secondary

End point timeframe

Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)
Week 16 (n=219, 0)	11.4 (7.5 to 16.4)	99999 (99999 to 99999)
Week 48 (n=219, 221)	11.4 (7.5 to 16.4)	14.5 (10.1 to 19.8)
Endpoint (LOCF) (n=219, 221)	11.9 (7.9 to 16.9)	15.4 (10.9 to 20.8)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Mucosal Healing at Weeks 16, 48, and Endpoint (LOCF)

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End point title

Percentage of Subjects With Mucosal Healing at Weeks 16, 48, and Endpoint (LOCF)

End point description

Mucosal healing defined as complete absence of mucosal ulcerations in any ileocolonic segment. SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. It 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. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. FRAS was used. Endpoint defined as last available postbaseline result within main analysis period (i.e, first 48 weeks). Here, 'n' (number analysed) included subjects analysed at specified timepoints. '99999' refers to data was not collected for routine care arm at Week 16 as per planned analysis.

End point type

Secondary

End point timeframe

Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)
Week 16 (n=219, 0)	16.0 (11.4 to 21.5)	99999 (99999 to 99999)
Week 48 (n=219,221)	14.2 (9.8 to 19.5)	16.7 (12.1 to 22.3)
Endpoint (LOCF) (n=219, 221)	14.6 (10.2 to 20.0)	17.6 (12.9 to 23.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (LOCF)

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End point title

Percentage of Subjects With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (LOCF)

End point description

Corticosteroid-free Clinical Remission at Week 48 and Endpoint (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 subjects 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. Subjects with missing data were analysed as non-remitter. LOCF: subjects who had a missing SES-CD score at Week 48 or who stopped treatment before reaching Week 48 had their last SES-CD score carried forward. FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study).

End point type

Secondary

End point timeframe

Week 48 and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)
Week 48	56.6 (49.8 to 63.3)	63.3 (56.6 to 69.7)
Endpoint (LOCF)	70.8 (64.3 to 76.7)	69.7 (63.2 to 75.7)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Corticosteroid-free Endoscopic Response at Week 16, 48, and Endpoint (LOCF)

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End point title

Percentage of Subjects With Corticosteroid-free Endoscopic Response at Week 16, 48, and Endpoint (LOCF)

End point description

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. SES-CD is validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. It 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. LOCF:subjects who had missing score or stopped treatment before Week 48 had last score carried forward. FRAS was used. Endpoint defined as last available postbaseline result within main analysis period (i.e, first 48 weeks).Here 'n' (number analysed) refers subjects analysed at specified timepoints. '99999' refers to data not collected as per planned analysis.

End point type

Secondary

End point timeframe

Week 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)
Week 16 (n=219, 0)	26.5 (20.8 to 32.9)	99999 (99999 to 99999)
Week 48 (n=219, 221)	33.8 (27.6 to 40.5)	28.5 (22.7 to 34.9)
Endpoint (LOCF) (n=219, 221)	36.1 (29.7 to 42.8)	29.4 (23.5 to 35.9)

No statistical analyses for this end point

Secondary: Change from Baseline in Serum C-reactive Protein (CRP)

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End point title

Change from Baseline in Serum C-reactive Protein (CRP)

End point description

Change from baseline in serum CRP were reported. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised. Here, 'N' (Number analysed) included subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	218	219
Units: Milligrams per litre (mg/L)
arithmetic mean (standard deviation)
Change at Week 16	-7.717 ( 22.0246 )	-7.345 ( 17.5658 )
Change at Week 48	-7.839 ( 22.6777 )	-7.909 ( 22.2139 )
Change at Endpoint (LOCF)	-7.839 ( 22.6777 )	-7.909 ( 22.2139 )

No statistical analyses for this end point

Secondary: Change from Baseline in Fecal Calprotectin (FC)

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End point title

Change from Baseline in Fecal Calprotectin (FC)

End point description

Change from baseline in FC were reported. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks of the study). FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised. Here, 'N' (Number analysed) included subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	196	189
Units: Micrograms per gram (mcg/g)
arithmetic mean (standard deviation)
Change at Week 16	-988.8 ( 3243.61 )	-728.2 ( 2238.60 )
Change at Week 48	-1191.6 ( 3441.64 )	-744.4 ( 2589.30 )
Change at Endpoint (LOCF)	-1191.6 ( 3441.64 )	-744.4 ( 2589.30 )

No statistical analyses for this end point

Secondary: Percentage of Subjects with Inflammatory Bowel Disease Questionnaire (IBDQ) Response

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End point title

Percentage of Subjects with Inflammatory Bowel Disease Questionnaire (IBDQ) Response

End point description

The IBDQ is 32-item questionnaire for subjects with Inflammatory Bowel Disease (IBD) used to evaluate disease-specific health-related quality of life. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). The 32 items were grouped into 4 domains: bowel function, emotional status, systemic symptoms and social function. The 4 domains were scored as follows: 10 to 70 (bowel symptoms); 5 to 35 (systemic symptoms); 12 to 84 (emotional function); and 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. Higher score means better quality of life. FRAS was used. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (that is, first 48 weeks).

End point type

Secondary

End point timeframe

Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Percentage of Subjects
number (confidence interval 95%)
Week 16	71.7 (65.2 to 77.6)	75.1 (68.9 to 80.7)
Week 48	58.4 (51.6 to 65.0)	67.0 (60.3 to 73.1)
Endpoint (LOCF)	77.2 (71.0 to 82.6)	77.8 (71.8 to 83.1)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Work Productivity and Activity Impairment (WPAI) Scores for Each Domain

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End point title

Percentage of Subjects With Work Productivity and Activity Impairment (WPAI) Scores for Each Domain

End point description

The WPAI questionnaire is a well-validated instrument of 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. The WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, worse outcomes. FRAS was used. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e, first 48 weeks). Here 'N' (Number analysed) refers subjects evaluable for this endpoint and 'n' (number analysed) refers to subjects analysed for specified categories. Subjects with missing data were analysed as no improvement.

End point type

Secondary

End point timeframe

Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	212	215
Units: Percentage of Subjects
number (confidence interval 95%)
Week 16: Absenteeism (n=86,96)	34.9 (24.9 to 45.9)	39.6 (29.7 to 50.1)
Week 48: Absenteeism (n=60,77)	35.0 (23.1 to 48.4)	36.4 (25.7 to 48.1)
Endpoint: Absenteeism (n=83,91)	34.9 (24.8 to 46.2)	36.3 (26.4 to 47.0)
Week 16: Presenteeism (n=105,104)	70.5 (60.8 to 79.0)	76.9 (67.6 to 84.6)
Week 48: Presenteeism (n=78,92)	73.1 (61.8 to 82.5)	72.8 (62.6 to 81.6)
Endpoint: Presenteeism (n=102,106)	69.6 (59.7 to 78.3)	69.8 (60.1 to 78.3)
Week 16: Work Productivity Loss (n=77,82)	71.4 (60.0 to 81.2)	70.7 (59.6 to 80.3)
Week 48: Work Productivity Loss (n=56,68)	75.0 (61.6 to 85.6)	72.1 (59.9 to 82.3)
Endpoint: Work Productivity Loss (n=76,79)	72.4 (60.9 to 82.0)	69.6 (58.2 to 79.5)
Week 16: Activity Impairment (n=204,207)	72.1 (65.4 to 78.1)	78.3 (72.0 to 83.7)
Week 48: Activity Impairment (n=156,178)	74.4 (66.8 to 81.0)	71.9 (64.7 to 78.4)
Endpoint: Activity Impairment (n=212,215)	67.9 (61.2 to 74.2)	70.7 (64.1 to 76.7)

No statistical analyses for this end point

Secondary: Change From Baseline in IBDQ Score

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End point title

Change From Baseline in IBDQ Score

End point description

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. FRAS was used. LOCF:subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint defined as last available postbaseline result within main analysis period (i.e first 48 weeks). Here, N (Number analysed) refers subjects evaluable for this endpoint. Only subjects with non-missing baseline value and at least one non-missing post-baseline value during main treatment period were included in analysis.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	214	217
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 16	41.3 ( 34.24 )	44.7 ( 33.20 )
Change at Week 48	43.7 ( 35.16 )	44.3 ( 36.94 )
Change at Endpoint (LOCF)	43.7 ( 35.16 )	44.3 ( 36.94 )

No statistical analyses for this end point

Secondary: Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Score

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End point title

Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Score

End point description

The EQ-5D-5L is a validated quality-of-life instrument which consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). A descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the subject current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. Higher scores representing a better health state. EQ-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (worst health) to 100 (best health). FRAS was used. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks). Here, N (Number analysed) refers subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	218	218
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 16	16.7 ( 20.19 )	18.7 ( 20.16 )
Change at Week 48	16.5 ( 22.77 )	16.1 ( 21.71 )
Change at Endpoint (LOCF)	16.5 ( 22.77 )	16.1 ( 21.71 )

No statistical analyses for this end point

Secondary: Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score

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End point title

Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score

End point description

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 fatigued to 4=not at all fatigued). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study). Here, 'N' (Number analysed) included subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	220
Units: Units on a scale
arithmetic mean (standard deviation)
Change at Week 16	9.1 ( 10.57 )	11.6 ( 10.12 )
Change at Week 48	9.9 ( 11.35 )	10.0 ( 11.11 )
Change at Endpoint (LOCF)	9.9 ( 11.35 )	10.0 ( 11.11 )

No statistical analyses for this end point

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS)

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End point title

Change From Baseline in Hospital Anxiety and Depression Scale (HADS)

End point description

The HADS 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). FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study). Here, 'N' (Number analysed) included subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	216	217
Units: Units on a scale
arithmetic mean (standard deviation)
Anxiety: Change at Week 16	-2.5 ( 3.43 )	-2.5 ( 3.88 )
Depression: Change at Week 16	-2.5 ( 3.59 )	-2.4 ( 3.41 )
Anxiety: Change at Week 48	-2.5 ( 3.64 )	-2.7 ( 4.05 )
Depression: Change at Week 48	-2.4 ( 4.00 )	-2.2 ( 3.97 )
Anxiety: Change at Endpoint (LOCF)	-2.5 ( 3.64 )	-2.7 ( 4.05 )
Depression: Change at Endpoint (LOCF)	-2.4 ( 4.00 )	-2.2 ( 3.97 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI Score

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End point title

Change From Baseline in WPAI Score

End point description

The WPAI questionnaire is a well-validated instrument with 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. FRAS population was used. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks). Here, 'N' (Number analysed) refers subjects evaluable for this endpoint and 'n' (number analysed) refers subjects analysed for specified categories.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	212	215
Units: Units on a scale
arithmetic mean (standard deviation)
Absenteeism: Change at Week 16 (n=86,96)	-12.9 ( 31.39 )	-12.5 ( 30.86 )
Absenteeism: Change at Week 48 (n=60,77)	-13.9 ( 34.13 )	-14.8 ( 30.22 )
Absenteeism: Change at Endpoint (n=83, 91)	-13.0 ( 34.87 )	-12.1 ( 31.92 )
Presenteeism: Change at Week 16: (n=105,104)	-23.3 ( 27.76 )	-26.2 ( 30.09 )
Presenteeism: Change at Week 48: (n=78,92)	-30.0 ( 31.83 )	-26.0 ( 28.90 )
Presenteeism: Change at Endpoint: (n=102,106)	-26.5 ( 30.50 )	-22.5 ( 30.99 )
Work Productivity Loss: Change at Week 16(n=77,82)	-25.2 ( 27.71 )	-27.2 ( 31.79 )
Work Productivity Loss: Change at Week 48(n=56,68)	-33.0 ( 33.98 )	-28.0 ( 31.66 )
Work Productivity Loss:Change at Endpoint(n=76,79)	-29.1 ( 32.91 )	-24.1 ( 33.97 )
Activity Impairment: Change at Week 16(n=204,207)	-24.1 ( 27.23 )	-27.3 ( 26.77 )
Activity Impairment: Change at Week 48(n=156,178)	-29.2 ( 29.65 )	-24.8 ( 28.96 )
Activity Impairment:Change at Endpoint(n=212, 215)	-25.5 ( 29.13 )	-23.6 ( 29.08 )

No statistical analyses for this end point

Secondary: Change From Baseline in Time Lost From Work

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End point title

Change From Baseline in Time Lost From Work

End point description

Time lost from work was collected by asking the subjects a single question, “How many days did you miss from work due to your Crohn’s disease in the last 4 weeks?” FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks of the study). Here, 'N' (Number analysed) included subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	133	139
Units: Days
arithmetic mean (standard deviation)
Change at Week 16	-1.7 ( 4.32 )	-1.8 ( 6.03 )
Change at Week 48	-1.8 ( 4.58 )	-2.2 ( 5.99 )
Change at Endpoint (LOCF)	-1.8 ( 4.58 )	-2.2 ( 5.99 )

No statistical analyses for this end point

Secondary: Number of Subjects With Adverse Events (AEs) That Occurred in Subjects Administered with Ustekinumab up to Week 48

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End point title

Number of Subjects With Adverse Events (AEs) That Occurred in Subjects Administered with Ustekinumab up to Week 48

End point description

An adverse event is any untoward medical event that occurs in subjects administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Subjects	188	179

No statistical analyses for this end point

Secondary: Change from Baseline in Body Weight

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End point title

Change from Baseline in Body Weight

End point description

Change from baseline in body weight were reported. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks). FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Kilograms (Kg)
arithmetic mean (standard deviation)
Change at Week 16	1.56 ( 2.996 )	1.16 ( 3.586 )
Change at Week 48	2.38 ( 4.682 )	1.39 ( 4.877 )
Change at Endpoint (LOCF)	2.38 ( 4.682 )	1.39 ( 4.877 )

No statistical analyses for this end point

Secondary: Change from Baseline in Body Mass index (BMI)

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End point title

Change from Baseline in Body Mass index (BMI)

End point description

Change from baseline in BMI were reported. BMI is a person’s weight (in kilograms) divided by the square of height (in meters). FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks).

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 48, Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Kilogram per meter square (Kg/m^2)
arithmetic mean (standard deviation)
Change at Week 16	0.54 ( 1.052 )	0.37 ( 1.236 )
Change at Week 48	0.82 ( 1.622 )	0.46 ( 1.665 )
Change at Endpoint (LOCF)	0.82 ( 1.622 )	0.46 ( 1.665 )

No statistical analyses for this end point

Secondary: Change from Baseline in Blood Pressure

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End point title

Change from Baseline in Blood Pressure

End point description

Change from baseline in Blood Pressure (Systolic Blood Pressure [SPB] and Diastolic Blood Pressure [DBP]) were reported. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks). FRAS included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Millimeter of mercury (mmHg)
arithmetic mean (standard deviation)
SBP: Change at Week 16	2.3 ( 13.16 )	0.3 ( 12.59 )
SBP: Change at Week 48	1.9 ( 13.21 )	0.5 ( 12.47 )
SBP: Change at Endpoint (LOCF)	1.9 ( 13.21 )	0.5 ( 12.47 )
DBP: Change at Week 16	1.1 ( 9.46 )	0.8 ( 9.81 )
DBP: Change at Week 48	1.2 ( 10.02 )	0.6 ( 9.85 )
DBP: Change at Endpoint (LOCF)	1.2 ( 10.02 )	0.6 ( 9.85 )

No statistical analyses for this end point

Secondary: Change from Baseline in Pulse Rate

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End point title

Change from Baseline in Pulse Rate

End point description

Change from baseline in pulse rate were reported. LOCF: subjects who had missing SES-CD score or stopped treatment before Week 48 had last SES-CD score carried forward. Endpoint is defined as the last available postbaseline result within the main analysis period (i.e. first 48 weeks). FRAS set included all subjects who received at least 1 dose of study agent and were randomized at Week 16, regardless of study treatment being administered once randomised.

End point type

Secondary

End point timeframe

Baseline, Weeks 16, 48, and Endpoint (LOCF)

End point values	Treat to Target	Routine Care
Number of subjects analysed	219	221
Units: Beats/minutes
arithmetic mean (standard deviation)
Change at Week 16	-1.5 ( 11.98 )	-2.0 ( 11.51 )
Change at Week 48	-0.2 ( 13.39 )	-1.7 ( 12.16 )
Change at Endpoint (LOCF)	-0.2 ( 13.39 )	-1.7 ( 12.16 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Induction Period= Baseline up to Week 16; Maintenance Period= Baseline up to Week 48; Extension Period/End of Study= Baseline up to Week 104

Adverse event reporting additional description

Induction period: Safety analysis set included subjects from FAS. Maintenance period: FRAS included subjects who got at least 1 dose of drug and randomised at Week 16, regardless of study treatment received once randomized. Extension period: Modified FAS included subjects randomised at Week 16 that completed Week 48 and entered extension period.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Maintenance Period: Treat to Target

Reporting group description

Reporting group title

Induction Period

Reporting group description

Reporting group title

Extension Period: Treat to Target

Reporting group description

From Week 48, subjects continued to received SC ustekinumab 90 mg in the long-term extension (LTE) period up to Week 104. The frequency of ustekinumab dosing with escalation/de-escalation between once in 12 weeks (q12w)/q8w/q4w was based on the following targets: endoscopic remission (CD [SES-CD] score less than or equal to [<=] 2) and corticosteroid (CS)-free clinical remission (CDAI score of <150 points of >=16 weeks duration) at Week 48; and later, on CS-free clinical remission and biomarker remission (C-reactive protein <=10 miligrams per liter [mg/L] and fecal calprotectin <=250 micrograms per gram [mcg/g]) at 2 consecutive visits 8 weeks apart. Subjects on q4w dosing failing to reach targets were discontinued.

Reporting group title

Extension Period: Routine Care

Reporting group description

From Week 48, subjects continued to received SC ustekinumab 90 mg in the long-term extension (LTE) period up to Week 104. The frequency of ustekinumab dosing with escalation/de-escalation between once in 12 weeks (q12w)/q8w/q4w was based on the following targets: endoscopic remission (CD [SES-CD] score <=2) and corticosteroid (CS)-free clinical remission (CDAI score of <150 points of >=16 weeks duration) at Week 48; and later, on CS-free clinical remission and biomarker remission (C-reactive protein <=10 mg/L and fecal calprotectin <=250 mcg/g) at 2 consecutive visits 8 weeks apart. Subjects on q4w dosing failing to reach targets were discontinued.

Reporting group title

Maintenance Period: Routine Care

Reporting group description

Serious adverse events	Maintenance Period: Treat to Target	Induction Period	Extension Period: Treat to Target	Extension Period: Routine Care	Maintenance Period: Routine Care
Total subjects affected by serious adverse events
subjects affected / exposed	26 / 219 (11.87%)	28 / 498 (5.62%)	21 / 147 (14.29%)	23 / 176 (13.07%)	29 / 221 (13.12%)
number of deaths (all causes)	2	0	0	1	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix Neoplasm
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Invasive Ductal Breast Carcinoma
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung Adenocarcinoma
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant Melanoma
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuroendocrine Carcinoma Metastatic
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Plasma Cell Myeloma
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Superficial Spreading Melanoma Stage Unspecified
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac Death
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Malaise
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-Cardiac Chest Pain
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Female Genital Tract Fistula
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metrorrhagia
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oropharyngeal Pain
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary Embolism
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Major Depression
subjects affected / exposed	1 / 219 (0.46%)	2 / 498 (0.40%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide Attempt
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Body Temperature Increased
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Head Injury
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Joint Dislocation
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina Pectoris
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac Failure Acute
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness Exertional
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Temporal Lobe Epilepsy
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	1 / 147 (0.68%)	2 / 176 (1.14%)	2 / 221 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal Fistula
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	1 / 176 (0.57%)	2 / 221 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Crohn's Disease
subjects affected / exposed	4 / 219 (1.83%)	6 / 498 (1.20%)	1 / 147 (0.68%)	4 / 176 (2.27%)	8 / 221 (3.62%)
occurrences causally related to treatment / all	0 / 4	0 / 7	0 / 1	1 / 4	1 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fistula of Small Intestine
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal Haemorrhage
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal Obstruction
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal Perforation
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal Stenosis
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intra-Abdominal Fluid Collection
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large Intestine Perforation
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large Intestine Polyp
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis Acute
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	2 / 176 (1.14%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back Pain
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteitis
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal Abscess
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal Wall Abscess
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abscess Intestinal
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal Abscess
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	1 / 147 (0.68%)	1 / 176 (0.57%)	3 / 221 (1.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bartholinitis
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter Infection
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Covid-19 Pneumonia
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis Infectious
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 219 (0.46%)	2 / 498 (0.40%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infectious Colitis
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large Intestine Infection
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Perirectal Abscess
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	1 / 147 (0.68%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Maintenance Period: Treat to Target	Induction Period	Extension Period: Treat to Target	Extension Period: Routine Care	Maintenance Period: Routine Care
Total subjects affected by non serious adverse events
subjects affected / exposed	158 / 219 (72.15%)	238 / 498 (47.79%)	125 / 147 (85.03%)	135 / 176 (76.70%)	150 / 221 (67.87%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 219 (0.46%)	3 / 498 (0.60%)	2 / 147 (1.36%)	5 / 176 (2.84%)	4 / 221 (1.81%)
occurrences all number	1	3	2	5	4
General disorders and administration site conditions
Asthenia
subjects affected / exposed	8 / 219 (3.65%)	10 / 498 (2.01%)	10 / 147 (6.80%)	8 / 176 (4.55%)	6 / 221 (2.71%)
occurrences all number	8	10	12	8	6
Fatigue
subjects affected / exposed	2 / 219 (0.91%)	3 / 498 (0.60%)	1 / 147 (0.68%)	5 / 176 (2.84%)	7 / 221 (3.17%)
occurrences all number	2	3	1	6	8
Influenza Like Illness
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	4 / 147 (2.72%)	2 / 176 (1.14%)	0 / 221 (0.00%)
occurrences all number	1	1	7	2	0
Pyrexia
subjects affected / exposed	25 / 219 (11.42%)	25 / 498 (5.02%)	15 / 147 (10.20%)	26 / 176 (14.77%)	19 / 221 (8.60%)
occurrences all number	37	33	25	35	21
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	3 / 219 (1.37%)	4 / 498 (0.80%)	3 / 147 (2.04%)	1 / 176 (0.57%)	2 / 221 (0.90%)
occurrences all number	3	4	3	1	2
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	8 / 219 (3.65%)	6 / 498 (1.20%)	6 / 147 (4.08%)	12 / 176 (6.82%)	7 / 221 (3.17%)
occurrences all number	9	6	8	15	8
Oropharyngeal Pain
subjects affected / exposed	5 / 219 (2.28%)	2 / 498 (0.40%)	8 / 147 (5.44%)	9 / 176 (5.11%)	5 / 221 (2.26%)
occurrences all number	8	2	11	9	5
Productive Cough
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	1 / 147 (0.68%)	4 / 176 (2.27%)	1 / 221 (0.45%)
occurrences all number	1	1	1	4	1
Psychiatric disorders
Anxiety
subjects affected / exposed	4 / 219 (1.83%)	2 / 498 (0.40%)	2 / 147 (1.36%)	6 / 176 (3.41%)	3 / 221 (1.36%)
occurrences all number	4	2	2	6	3
Depression
subjects affected / exposed	0 / 219 (0.00%)	3 / 498 (0.60%)	1 / 147 (0.68%)	4 / 176 (2.27%)	5 / 221 (2.26%)
occurrences all number	0	3	1	4	5
Insomnia
subjects affected / exposed	4 / 219 (1.83%)	1 / 498 (0.20%)	4 / 147 (2.72%)	5 / 176 (2.84%)	3 / 221 (1.36%)
occurrences all number	4	1	6	5	3
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	0 / 147 (0.00%)	4 / 176 (2.27%)	3 / 221 (1.36%)
occurrences all number	0	0	0	4	3
C-Reactive Protein Increased
subjects affected / exposed	4 / 219 (1.83%)	6 / 498 (1.20%)	3 / 147 (2.04%)	1 / 176 (0.57%)	2 / 221 (0.90%)
occurrences all number	4	6	3	2	2
Serum Ferritin Decreased
subjects affected / exposed	2 / 219 (0.91%)	0 / 498 (0.00%)	5 / 147 (3.40%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences all number	2	0	6	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	2 / 219 (0.91%)	2 / 498 (0.40%)	3 / 147 (2.04%)	2 / 176 (1.14%)	2 / 221 (0.90%)
occurrences all number	2	2	3	2	2
Ligament Sprain
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	2 / 147 (1.36%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	1	1	2	4	2
Procedural Pain
subjects affected / exposed	2 / 219 (0.91%)	0 / 498 (0.00%)	3 / 147 (2.04%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences all number	2	0	3	0	0
Nervous system disorders
Headache
subjects affected / exposed	24 / 219 (10.96%)	36 / 498 (7.23%)	20 / 147 (13.61%)	28 / 176 (15.91%)	21 / 221 (9.50%)
occurrences all number	42	47	62	92	51
Migraine
subjects affected / exposed	0 / 219 (0.00%)	3 / 498 (0.60%)	0 / 147 (0.00%)	6 / 176 (3.41%)	2 / 221 (0.90%)
occurrences all number	0	3	0	6	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	8 / 219 (3.65%)	14 / 498 (2.81%)	8 / 147 (5.44%)	8 / 176 (4.55%)	11 / 221 (4.98%)
occurrences all number	10	14	10	10	13
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	3 / 219 (1.37%)	3 / 498 (0.60%)	3 / 147 (2.04%)	0 / 176 (0.00%)	2 / 221 (0.90%)
occurrences all number	3	3	3	0	2
Eye disorders
Cataract
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	3 / 147 (2.04%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences all number	1	0	3	0	1
Dry Eye
subjects affected / exposed	1 / 219 (0.46%)	2 / 498 (0.40%)	1 / 147 (0.68%)	4 / 176 (2.27%)	3 / 221 (1.36%)
occurrences all number	1	2	1	5	3
Gastrointestinal disorders
Abdominal Distension
subjects affected / exposed	3 / 219 (1.37%)	5 / 498 (1.00%)	3 / 147 (2.04%)	6 / 176 (3.41%)	6 / 221 (2.71%)
occurrences all number	4	5	5	8	7
Abdominal Pain
subjects affected / exposed	23 / 219 (10.50%)	18 / 498 (3.61%)	23 / 147 (15.65%)	22 / 176 (12.50%)	17 / 221 (7.69%)
occurrences all number	31	26	36	34	22
Abdominal Pain Upper
subjects affected / exposed	7 / 219 (3.20%)	6 / 498 (1.20%)	7 / 147 (4.76%)	4 / 176 (2.27%)	4 / 221 (1.81%)
occurrences all number	7	7	8	8	6
Anal Fissure
subjects affected / exposed	1 / 219 (0.46%)	3 / 498 (0.60%)	1 / 147 (0.68%)	4 / 176 (2.27%)	6 / 221 (2.71%)
occurrences all number	1	3	1	5	6
Anal Fistula
subjects affected / exposed	2 / 219 (0.91%)	2 / 498 (0.40%)	3 / 147 (2.04%)	3 / 176 (1.70%)	4 / 221 (1.81%)
occurrences all number	2	2	4	4	5
Constipation
subjects affected / exposed	4 / 219 (1.83%)	7 / 498 (1.41%)	4 / 147 (2.72%)	6 / 176 (3.41%)	6 / 221 (2.71%)
occurrences all number	5	8	5	7	7
Crohn's Disease
subjects affected / exposed	16 / 219 (7.31%)	9 / 498 (1.81%)	18 / 147 (12.24%)	20 / 176 (11.36%)	21 / 221 (9.50%)
occurrences all number	17	10	19	22	24
Diarrhoea
subjects affected / exposed	11 / 219 (5.02%)	9 / 498 (1.81%)	17 / 147 (11.56%)	17 / 176 (9.66%)	13 / 221 (5.88%)
occurrences all number	13	10	21	24	15
Dyspepsia
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	1 / 147 (0.68%)	5 / 176 (2.84%)	3 / 221 (1.36%)
occurrences all number	1	0	1	9	7
Flatulence
subjects affected / exposed	4 / 219 (1.83%)	0 / 498 (0.00%)	4 / 147 (2.72%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	5	0	6	4	2
Frequent Bowel Movements
subjects affected / exposed	2 / 219 (0.91%)	3 / 498 (0.60%)	1 / 147 (0.68%)	5 / 176 (2.84%)	3 / 221 (1.36%)
occurrences all number	2	3	1	5	3
Gastrooesophageal Reflux Disease
subjects affected / exposed	4 / 219 (1.83%)	2 / 498 (0.40%)	3 / 147 (2.04%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	4	2	3	4	2
Haematochezia
subjects affected / exposed	2 / 219 (0.91%)	0 / 498 (0.00%)	2 / 147 (1.36%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	2	0	3	4	2
Haemorrhoids
subjects affected / exposed	2 / 219 (0.91%)	1 / 498 (0.20%)	1 / 147 (0.68%)	6 / 176 (3.41%)	3 / 221 (1.36%)
occurrences all number	2	1	1	8	3
Nausea
subjects affected / exposed	12 / 219 (5.48%)	12 / 498 (2.41%)	11 / 147 (7.48%)	16 / 176 (9.09%)	12 / 221 (5.43%)
occurrences all number	18	16	13	21	15
Toothache
subjects affected / exposed	5 / 219 (2.28%)	3 / 498 (0.60%)	6 / 147 (4.08%)	4 / 176 (2.27%)	4 / 221 (1.81%)
occurrences all number	6	3	7	4	5
Vomiting
subjects affected / exposed	9 / 219 (4.11%)	7 / 498 (1.41%)	5 / 147 (3.40%)	11 / 176 (6.25%)	9 / 221 (4.07%)
occurrences all number	10	10	6	12	12
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	5 / 219 (2.28%)	6 / 498 (1.20%)	4 / 147 (2.72%)	4 / 176 (2.27%)	4 / 221 (1.81%)
occurrences all number	5	6	4	4	4
Eczema
subjects affected / exposed	4 / 219 (1.83%)	3 / 498 (0.60%)	4 / 147 (2.72%)	2 / 176 (1.14%)	1 / 221 (0.45%)
occurrences all number	4	3	5	2	1
Erythema
subjects affected / exposed	4 / 219 (1.83%)	4 / 498 (0.80%)	4 / 147 (2.72%)	4 / 176 (2.27%)	3 / 221 (1.36%)
occurrences all number	4	5	6	5	4
Pruritus
subjects affected / exposed	4 / 219 (1.83%)	4 / 498 (0.80%)	5 / 147 (3.40%)	2 / 176 (1.14%)	2 / 221 (0.90%)
occurrences all number	4	4	5	3	3
Rash
subjects affected / exposed	5 / 219 (2.28%)	3 / 498 (0.60%)	9 / 147 (6.12%)	7 / 176 (3.98%)	7 / 221 (3.17%)
occurrences all number	6	3	10	9	8
Skin Lesion
subjects affected / exposed	1 / 219 (0.46%)	1 / 498 (0.20%)	3 / 147 (2.04%)	0 / 176 (0.00%)	1 / 221 (0.45%)
occurrences all number	1	1	3	0	1
Renal and urinary disorders
Renal Colic
subjects affected / exposed	2 / 219 (0.91%)	0 / 498 (0.00%)	3 / 147 (2.04%)	1 / 176 (0.57%)	2 / 221 (0.90%)
occurrences all number	2	0	4	1	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	24 / 219 (10.96%)	29 / 498 (5.82%)	24 / 147 (16.33%)	26 / 176 (14.77%)	19 / 221 (8.60%)
occurrences all number	30	31	29	35	22
Arthritis
subjects affected / exposed	4 / 219 (1.83%)	2 / 498 (0.40%)	3 / 147 (2.04%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences all number	4	2	3	1	0
Back Pain
subjects affected / exposed	7 / 219 (3.20%)	11 / 498 (2.21%)	15 / 147 (10.20%)	18 / 176 (10.23%)	12 / 221 (5.43%)
occurrences all number	8	11	17	25	12
Myalgia
subjects affected / exposed	5 / 219 (2.28%)	6 / 498 (1.20%)	6 / 147 (4.08%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	7	7	8	5	2
Neck Pain
subjects affected / exposed	1 / 219 (0.46%)	3 / 498 (0.60%)	2 / 147 (1.36%)	7 / 176 (3.98%)	4 / 221 (1.81%)
occurrences all number	1	3	2	13	4
Pain in Extremity
subjects affected / exposed	2 / 219 (0.91%)	1 / 498 (0.20%)	3 / 147 (2.04%)	1 / 176 (0.57%)	0 / 221 (0.00%)
occurrences all number	2	1	3	1	0
Infections and infestations
Anal Abscess
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	0 / 147 (0.00%)	5 / 176 (2.84%)	3 / 221 (1.36%)
occurrences all number	1	0	0	5	3
Bronchitis
subjects affected / exposed	4 / 219 (1.83%)	5 / 498 (1.00%)	4 / 147 (2.72%)	11 / 176 (6.25%)	8 / 221 (3.62%)
occurrences all number	7	5	7	15	10
Gastroenteritis
subjects affected / exposed	7 / 219 (3.20%)	5 / 498 (1.00%)	12 / 147 (8.16%)	9 / 176 (5.11%)	5 / 221 (2.26%)
occurrences all number	7	5	12	9	5
Covid-19
subjects affected / exposed	0 / 219 (0.00%)	0 / 498 (0.00%)	5 / 147 (3.40%)	3 / 176 (1.70%)	0 / 221 (0.00%)
occurrences all number	0	0	5	3	0
Gastroenteritis Viral
subjects affected / exposed	4 / 219 (1.83%)	1 / 498 (0.20%)	3 / 147 (2.04%)	5 / 176 (2.84%)	3 / 221 (1.36%)
occurrences all number	4	1	3	5	3
Gastrointestinal Infection
subjects affected / exposed	1 / 219 (0.46%)	0 / 498 (0.00%)	3 / 147 (2.04%)	2 / 176 (1.14%)	0 / 221 (0.00%)
occurrences all number	1	0	3	2	0
Influenza
subjects affected / exposed	12 / 219 (5.48%)	13 / 498 (2.61%)	14 / 147 (9.52%)	14 / 176 (7.95%)	11 / 221 (4.98%)
occurrences all number	13	13	15	16	12
Nasopharyngitis
subjects affected / exposed	29 / 219 (13.24%)	44 / 498 (8.84%)	23 / 147 (15.65%)	35 / 176 (19.89%)	29 / 221 (13.12%)
occurrences all number	48	48	46	58	39
Oral Herpes
subjects affected / exposed	5 / 219 (2.28%)	6 / 498 (1.20%)	4 / 147 (2.72%)	2 / 176 (1.14%)	2 / 221 (0.90%)
occurrences all number	5	6	6	5	3
Pharyngitis
subjects affected / exposed	9 / 219 (4.11%)	3 / 498 (0.60%)	7 / 147 (4.76%)	10 / 176 (5.68%)	7 / 221 (3.17%)
occurrences all number	11	3	9	10	7
Sinusitis
subjects affected / exposed	3 / 219 (1.37%)	5 / 498 (1.00%)	1 / 147 (0.68%)	5 / 176 (2.84%)	2 / 221 (0.90%)
occurrences all number	4	5	1	8	2
Rhinitis
subjects affected / exposed	3 / 219 (1.37%)	2 / 498 (0.40%)	1 / 147 (0.68%)	6 / 176 (3.41%)	4 / 221 (1.81%)
occurrences all number	3	2	1	7	5
Tonsillitis
subjects affected / exposed	3 / 219 (1.37%)	2 / 498 (0.40%)	5 / 147 (3.40%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	3	2	7	5	2
Tooth Abscess
subjects affected / exposed	3 / 219 (1.37%)	1 / 498 (0.20%)	6 / 147 (4.08%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	4	1	7	7	3
Upper Respiratory Tract Infection
subjects affected / exposed	4 / 219 (1.83%)	6 / 498 (1.20%)	4 / 147 (2.72%)	8 / 176 (4.55%)	4 / 221 (1.81%)
occurrences all number	6	7	6	8	4
Urinary Tract Infection
subjects affected / exposed	3 / 219 (1.37%)	5 / 498 (1.00%)	5 / 147 (3.40%)	5 / 176 (2.84%)	4 / 221 (1.81%)
occurrences all number	3	5	5	12	7
Vaginal Infection
subjects affected / exposed	2 / 219 (0.91%)	0 / 498 (0.00%)	3 / 147 (2.04%)	0 / 176 (0.00%)	0 / 221 (0.00%)
occurrences all number	2	0	3	0	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	4 / 219 (1.83%)	4 / 498 (0.80%)	2 / 147 (1.36%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	4	4	2	4	2
Folate Deficiency
subjects affected / exposed	2 / 219 (0.91%)	1 / 498 (0.20%)	4 / 147 (2.72%)	5 / 176 (2.84%)	5 / 221 (2.26%)
occurrences all number	2	1	4	5	5
Hypokalaemia
subjects affected / exposed	0 / 219 (0.00%)	1 / 498 (0.20%)	0 / 147 (0.00%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	0	1	0	4	2
Hypophosphataemia
subjects affected / exposed	3 / 219 (1.37%)	2 / 498 (0.40%)	3 / 147 (2.04%)	1 / 176 (0.57%)	1 / 221 (0.45%)
occurrences all number	3	2	4	1	1
Iron Deficiency
subjects affected / exposed	3 / 219 (1.37%)	2 / 498 (0.40%)	3 / 147 (2.04%)	2 / 176 (1.14%)	3 / 221 (1.36%)
occurrences all number	3	2	3	2	3
Vitamin B12 Deficiency
subjects affected / exposed	3 / 219 (1.37%)	1 / 498 (0.20%)	6 / 147 (4.08%)	4 / 176 (2.27%)	2 / 221 (0.90%)
occurrences all number	3	1	6	4	2
Vitamin D Deficiency
subjects affected / exposed	3 / 219 (1.37%)	2 / 498 (0.40%)	6 / 147 (4.08%)	7 / 176 (3.98%)	6 / 221 (2.71%)
occurrences all number	5	2	9	7	6

More information

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Were there any global substantial amendments to the protocol? Yes

22 Mar 2017

To redefine the treatment target according to more stringent Crohn’s Disease Activity Index (CDAI) and biomarker criteria as recommended by the study steering committee and considered scientifically more valid in the context of a treat to target strategy.

13 Sep 2017

To redefine the treatment target for subjects who did not have elevated C-reactive protein (CRP) at baseline.

23 Nov 2017

To extend study treatment to Week 104, to explore the effectiveness of longer-term ustekinumab treatment, and to explore de-escalation of ustekinumab dosing.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Study was limited by open-label design and randomisation of CDAI-70 responders at Week 16 only, that partly explain high Week 48 response rates.

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Clinical trials

Clinical Trial Results: Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn’s Disease Patients Treated with Ustekinumab

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Endoscopic Response at Week 48

Primary: Percentage of Subjects With Endoscopic Response at Week 48

Secondary: Percentage of Subjects With Endoscopic Response at Week 48 (Premature Drop-outs Excluded)

Secondary: Percentage of Subjects With Endoscopic Response at Week 48 (Premature Drop-outs Excluded)

Secondary: Percentage of Subjects With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF])

Secondary: Percentage of Subjects With Endoscopic Response at Week 48 (Last Observation Carried Forward [LOCF])

Secondary: Percentage of Subjects With Clinical Response at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Clinical Response at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Clinical Remission at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Clinical Remission at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Endoscopic Remission at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Endoscopic Remission at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Mucosal Healing at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Mucosal Healing at Weeks 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (LOCF)

Secondary: Percentage of Subjects With Corticosteroid-free Clinical Remission at Week 48 and Endpoint (LOCF)

Secondary: Percentage of Subjects With Corticosteroid-free Endoscopic Response at Week 16, 48, and Endpoint (LOCF)

Secondary: Percentage of Subjects With Corticosteroid-free Endoscopic Response at Week 16, 48, and Endpoint (LOCF)

Secondary: Change from Baseline in Serum C-reactive Protein (CRP)

Secondary: Change from Baseline in Serum C-reactive Protein (CRP)

Secondary: Change from Baseline in Fecal Calprotectin (FC)

Secondary: Change from Baseline in Fecal Calprotectin (FC)

Secondary: Percentage of Subjects with Inflammatory Bowel Disease Questionnaire (IBDQ) Response

Secondary: Percentage of Subjects with Inflammatory Bowel Disease Questionnaire (IBDQ) Response

Secondary: Percentage of Subjects With Work Productivity and Activity Impairment (WPAI) Scores for Each Domain

Secondary: Percentage of Subjects With Work Productivity and Activity Impairment (WPAI) Scores for Each Domain

Secondary: Change From Baseline in IBDQ Score

Secondary: Change From Baseline in IBDQ Score

Secondary: Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Score

Secondary: Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Score

Secondary: Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score

Secondary: Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale Score

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS)

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS)

Secondary: Change From Baseline in WPAI Score

Secondary: Change From Baseline in WPAI Score

Secondary: Change From Baseline in Time Lost From Work

Secondary: Change From Baseline in Time Lost From Work

Secondary: Number of Subjects With Adverse Events (AEs) That Occurred in Subjects Administered with Ustekinumab up to Week 48

Secondary: Number of Subjects With Adverse Events (AEs) That Occurred in Subjects Administered with Ustekinumab up to Week 48

Secondary: Change from Baseline in Body Weight

Secondary: Change from Baseline in Body Weight

Secondary: Change from Baseline in Body Mass index (BMI)

Secondary: Change from Baseline in Body Mass index (BMI)

Secondary: Change from Baseline in Blood Pressure

Secondary: Change from Baseline in Blood Pressure

Secondary: Change from Baseline in Pulse Rate

Secondary: Change from Baseline in Pulse Rate

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn’s Disease Patients Treated with Ustekinumab