Trial Outcomes & Findings for Loss of RESponse to Ustekinumab Treated by Dose Escalation (NCT NCT04245215)

Last Updated: 2026-04-13

Results Overview

Proportion of patients with steroid free clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) and fecal calprotectin\<250µg/g at week 48. \[stool frequency (ST): average number of liquid stools for 1 week abdominal pain (AP): average scoring for abdominal pain for 1 week (0=none; 1=mild, 2=moderate; 3= severe)\]

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

108 participants

Primary outcome timeframe

week 48

Results posted on

2026-04-13

Participant Flow

Between February 2020 and October 2023 a total of 132 patients were screened and 108 patients were randomized. First Patient In (FPI) was on 11Mar2020. Last Patient In (LPI) was on 17Oct2023. Last Patient Out (LPO) was on 25Sep2024.

Eligible Crohn's Disease patients were treated with ustekinumab at a standard maintenance dose of 90 mg every 8 weeks SC. Patients needed to have a documented primary response to standard IV induction with ustekinumab and a documented secondary loss of response based on Patient-Reported Outcomes and objective documentation of disease activity.

Participant milestones

Participant milestones
Measure	Ustekinumab q4w Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Overall Study STARTED	54	54
Overall Study COMPLETED	37	35
Overall Study NOT COMPLETED	17	19

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Loss of RESponse to Ustekinumab Treated by Dose Escalation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ustekinumab q4w n=54 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=54 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).	Total n=108 Participants Total of all reporting groups
Age, Continuous	41 years n=193 Participants	40 years n=193 Participants	41 years n=386 Participants
Sex: Female, Male Female	35 Participants n=193 Participants	32 Participants n=193 Participants	67 Participants n=386 Participants
Sex: Female, Male Male	19 Participants n=193 Participants	22 Participants n=193 Participants	41 Participants n=386 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=193 Participants	54 Participants n=193 Participants	108 Participants n=386 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=193 Participants	0 Participants n=193 Participants	0 Participants n=386 Participants

PRIMARY outcome

Timeframe: week 48

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=54 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=54 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Steroid Free Clinical Remission and Fecal Calprotectin<250µg/g at Week 48	8 Participants	10 Participants

SECONDARY outcome

Timeframe: week 48

Proportion of patients with complete endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD )\<3) at week 48

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=51 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=50 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Complete Endoscopic Remission at Week 48	4 Participants	3 Participants

SECONDARY outcome

Timeframe: week 48

Proportion of patients with endoscopic remission (simple endoscopic score for Crohn's disease (SES-CD) \<5) at week 48

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=51 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=50 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Endoscopic Remission at Week 48	15 Participants	8 Participants

SECONDARY outcome

Timeframe: week 48

Proportion of patients with endoscopic response (≥50% decrease in simple endoscopic score for Crohn's disease (SES-CD)) at week 48

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=51 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=50 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Endoscopic Response at Week 48	12 Participants	8 Participants

SECONDARY outcome

Timeframe: week 8

Proportion of patients with clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) at week 8

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=53 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=54 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Clinical Remission at Week 8	19 Participants	21 Participants

SECONDARY outcome

Timeframe: week 48

Proportion of patients with clinical remission (patient reported outcome-2 remission: abdominal pain ≤ 1 AND stool frequency ≤ 3) at week 48

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=52 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=50 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Clinical Remission at Week 48	16 Participants	18 Participants

SECONDARY outcome

Timeframe: week 48

Proportion of patients with biomarker remission (C-reactive protein \<5 mg/L and fecal calprotectin \<250 µg/g) at week 48

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=50 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=50 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Biomarker Remission at Week 48	18 Participants	13 Participants

SECONDARY outcome

Timeframe: Week 48

Proportion of patients with serious adverse events at week 48

Outcome measures

Outcome measures
Measure	Ustekinumab q4w n=54 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=54 Participants Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Proportion of Patients With Serious Adverse Events at Week 48	9 Participants	7 Participants

Adverse Events

Ustekinumab q4w

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Ustekinumab q8w

Serious events: 7 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ustekinumab q4w n=54 participants at risk Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=54 participants at risk Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Nervous system disorders headache	9.3% 5/54 • Number of events 8 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.0% 7/54 • Number of events 8 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders fatigue	14.8% 8/54 • Number of events 8 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	9.3% 5/54 • Number of events 5 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders gastro-enteritis	7.4% 4/54 • Number of events 4 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.4% 4/54 • Number of events 5 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Worsening of Crohn's Disease	11.1% 6/54 • Number of events 6 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	7.4% 4/54 • Number of events 5 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	18.5% 10/54 • Number of events 11 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	24.1% 13/54 • Number of events 14 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Skin abnormalities	11.1% 6/54 • Number of events 6 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	16.7% 9/54 • Number of events 11 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders psychiatric symptoms	9.3% 5/54 • Number of events 7 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.6% 3/54 • Number of events 5 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders musculoskeletal and connective tissue disorders	33.3% 18/54 • Number of events 24 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	40.7% 22/54 • Number of events 42 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations respiratory infection	38.9% 21/54 • Number of events 35 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	46.3% 25/54 • Number of events 32 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations flu	13.0% 7/54 • Number of events 9 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.8% 8/54 • Number of events 9 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders lab abnormalities/deficiencies	18.5% 10/54 • Number of events 12 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	27.8% 15/54 • Number of events 22 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Ingrid Arijs

Belgian IBD Research and Development (BIRD)

Phone: 0499317005

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee According to the clinical study agreement, the sponsor owns the study data and prepares the study report. Investigators must comply with confidentiality and publication provisions, which remain in effect after completion of the study.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ustekinumab q4w n=54 participants at risk Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q4w arm received the first blinded 90 mg SC injection of ustekinumab. Subsequently, subjects in the q4w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded active ustekinumab (at week 12, 20, 28, 36, 44).	Ustekinumab q8w n=54 participants at risk Subjects received a re-induction at baseline, with intravenous ustekinumab, in line with the EU SmPC, on a weight-tiered basis at a dose of approximately 6 mg/kg. At week 4, the subjects in the q8w arm received the first blinded placebo injection. Subsequently, subjects in the q8w arm received commercial available q8w ustekinumab (90 mg SC syringe at week 8, 16, 24, 32, 40, 48) alternated with q8w double blinded placebo (at week 12, 20, 28, 36, 44).
Gastrointestinal disorders Small bowel ileus	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders (sub)obstruction	5.6% 3/54 • Number of events 3 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations E. Coli urosepsis	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications abdominal pain after right hemicolectomy	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Surgical and medical procedures Cardiac Ablation	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Surgical and medical procedures Laparoscopic right hemicolectomy	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Extensive colitis	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders gastro-enteritis	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.7% 2/54 • Number of events 2 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Bowel obstruction terminal ileitis	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Flare of Crohn's Disease	3.7% 2/54 • Number of events 2 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Presacral abscess	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 2 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Stricturing Crohn's Disease	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholangitis	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 2 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Stenosis Hepaticojejunostomia	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Infection Giardia Lamblia	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders electrolyte abnormalities	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Stress fracture femoral neck left	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia due to infliximab	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Recurrent abdominal wall hernia	0.00% 0/54 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.9% 1/54 • Number of events 1 • From signature of informed consent form up to week 48 in the study. For SAE's up to 60 days after the last study treatment. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.