Trial Outcomes & Findings for Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year (NCT NCT03464136)

Last Updated: 2025-04-29

Results Overview

Percentage of participants with clinical remission at Week 52 were assessed. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than (\<) 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

386 participants

Primary outcome timeframe

Week 52

Results posted on

2025-04-29

Participant Flow

Participant milestones

Participant milestones
Measure	Adalimumab Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Overall Study STARTED	195	191
Overall Study COMPLETED	165	166
Overall Study NOT COMPLETED	30	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Adalimumab Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Overall Study Lost to Follow-up	5	8
Overall Study Withdrawal by Subject	16	13
Overall Study Death	1	0
Overall Study Other	8	4

Baseline Characteristics

Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.	Total n=386 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 12.99 • n=5 Participants	37 years STANDARD_DEVIATION 13.23 • n=7 Participants	37.2 years STANDARD_DEVIATION 13.09 • n=5 Participants
Sex: Female, Male Female	100 Participants n=5 Participants	101 Participants n=7 Participants	201 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	90 Participants n=7 Participants	185 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	178 Participants n=5 Participants	173 Participants n=7 Participants	351 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	11 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	181 Participants n=5 Participants	164 Participants n=7 Participants	345 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Australia	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Belgium	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Brazil	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment Bulgaria	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Canada	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Czech Republic	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Region of Enrollment France	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Germany	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Hungary	16 Participants n=5 Participants	13 Participants n=7 Participants	29 Participants n=5 Participants
Region of Enrollment Italy	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Poland	34 Participants n=5 Participants	26 Participants n=7 Participants	60 Participants n=5 Participants
Region of Enrollment Republic of Korea	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Russia	27 Participants n=5 Participants	20 Participants n=7 Participants	47 Participants n=5 Participants
Region of Enrollment Serbia	10 Participants n=5 Participants	2 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Spain	4 Participants n=5 Participants	14 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment United Kingdom	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States of America	31 Participants n=5 Participants	36 Participants n=7 Participants	67 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 52

Population: Full analysis set (FAS) which was defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Clinical Remission at Week 52	61.0 percentage of participants	64.9 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: FAS which was defined as all randomized participants.

Percentage of participants with Corticosteroid-free remission at Week 52 were assessed. Corticosteroid-free remission was defined as CDAI score \<150 points at Week 52 and not taking any corticosteroids for at least 30 days prior to Week 52. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Corticosteroid-free Remission at Week 52	57.4 percentage of participants	60.7 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: FAS which was defined as all randomized participants.

Percentage of participants with clinical response at Week 52 were assessed. Clinical response at Week 52 was defined as a reduction from baseline in the CDAI score of greater than or equal (\>=) 100 points. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Clinical Response at Week 52	66.2 percentage of participants	72.3 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: FAS which was defined as all randomized participants.

PRO2 evaluated 2 patient-reported symptoms: the frequency of liquid or soft stools (total number of soft/liquid stools in the last 7 days) and abdominal pain (on a 4-point scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe). A weekly score was calculated for the liquid or soft stool frequency and a separate weekly score was calculated for abdominal pain, in each case based on daily symptom reporting. PRO-2 symptom remission was defined as an abdominal pain (AP) mean daily score at or below 1 and also stool frequency (SF) mean daily score at or below 3, that is, AP \<=1 and SF \<=3. PRO2 is a composite index consisting of weighted scoring of both variables. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants in Patient Reported Outcome (PRO)-2 Symptom Remission at Week 52	55.4 percentage of participants	56.5 percentage of participants

SECONDARY outcome

Timeframe: Week 16

Population: FAS which was defined as all randomized participants.

Percentage of participants with clinical remission (defined as CDAI \<150 points) at Week 16 were assessed. Clinical remission was defined as a CDAI score of \< 150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Clinical Remission at Week 16	60 percentage of participants	57.1 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: FAS among participants with SES-CD Score \>=3 at Baseline.

Percentage of participants with endoscopic remission at Week 52 were assessed. Endoscopic remission was defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) score less than or equal to (\<=) 3, or SES-CD =0 for participants who entered the study with a SES-CD =3 at Week 52. The SES-CD evaluates 4 endoscopic variables (ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis) each rated from 0 (best) to 3 (worst) in 5 segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable is the sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease.

Outcome measures

Outcome measures
Measure	Adalimumab n=179 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=179 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Endoscopic Remission at Week 52	30.7 percentage of participants	28.5 percentage of participants

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 24, 32, 40, 48, and 52

Population: FAS which was defined as all randomized participants.

Percentage of participants with clinical remission at each postbaseline visit through Week 52 were reported. Clinical remission was defined as a CDAI score of \<150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Clinical Remission Through Week 52 Week 2	28.7 percentage of participants	23.0 percentage of participants
Percentage of Participants With Clinical Remission Through Week 52 Week 8	47.7 percentage of participants	50.3 percentage of participants
Percentage of Participants With Clinical Remission Through Week 52 Week 16	60.0 percentage of participants	57.1 percentage of participants
Percentage of Participants With Clinical Remission Through Week 52 Week 24	66.2 percentage of participants	57.6 percentage of participants
Percentage of Participants With Clinical Remission Through Week 52 Week 32	65.1 percentage of participants	59.7 percentage of participants
Percentage of Participants With Clinical Remission Through Week 52 Week 40	60.5 percentage of participants	64.9 percentage of participants
Percentage of Participants With Clinical Remission Through Week 52 Week 48	59.0 percentage of participants	62.8 percentage of participants
Percentage of Participants With Clinical Remission Through Week 52 Week 52	61.0 percentage of participants	64.9 percentage of participants

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 24, 32, 40, 48, and 52

Population: FAS which was defined as all randomized participants.

Percentage of participants with clinical response at each postbaseline visit through Week 52 were reported. Clinical response through Week 52 was defined as a reduction from baseline in the CDAI score of \>=100 points. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Clinical Response Through Week 52 Week 52	66.2 percentage of participants	72.3 percentage of participants
Percentage of Participants With Clinical Response Through Week 52 Week 2	46.2 percentage of participants	38.2 percentage of participants
Percentage of Participants With Clinical Response Through Week 52 Week 8	66.2 percentage of participants	68.1 percentage of participants
Percentage of Participants With Clinical Response Through Week 52 Week 16	72.3 percentage of participants	73.3 percentage of participants
Percentage of Participants With Clinical Response Through Week 52 Week 24	76.4 percentage of participants	70.7 percentage of participants
Percentage of Participants With Clinical Response Through Week 52 Week 32	74.9 percentage of participants	71.2 percentage of participants
Percentage of Participants With Clinical Response Through Week 52 Week 40	69.2 percentage of participants	74.3 percentage of participants
Percentage of Participants With Clinical Response Through Week 52 Week 48	66.7 percentage of participants	69.1 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: FAS which was defined as all randomized participants.

Percentage of participants with durable clinical response at Week 52 were reported. Durable clinical response was defined as CDAI score decreased at least 100 from baseline or CDAI \<150 at Week 52 and was \>= 80% of all visits between Week 16 and Week 52. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Durable Clinical Response at Week 52	60.5 percentage of participants	65.4 percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: FAS which was defined as all randomized participants.

Percentage of participants with durable clinical remission at Week 52 were reported. Clinical remission was defined as CDAI score \<150 at Week 52 and was \>= 80% of all visits between Week 16 and Week 52. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Durable Clinical Remission at Week 52	51.8 percentage of participants	50.8 percentage of participants

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 24, 32, 40, 48, and 52

Population: FAS among participants with mean daily AP Score \>0 at Baseline.

Percentage of participants with AP improvement through Week 52 were reported. AP improvement was defined as at least 1 point or greater improvement in mean daily CDAI AP score (ranges from 0 to 3 where higher score indicates severity of pain) from baseline, or a mean score of zero among participants with mean AP\>0 at baseline, compared at each visit through Week 52.

Outcome measures

Outcome measures
Measure	Adalimumab n=194 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 2	29.9 percentage of participants	23.0 percentage of participants
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 8	54.1 percentage of participants	53.9 percentage of participants
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 16	62.9 percentage of participants	59.2 percentage of participants
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 24	66.5 percentage of participants	61.8 percentage of participants
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 32	63.9 percentage of participants	63.9 percentage of participants
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 40	60.3 percentage of participants	63.9 percentage of participants
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 48	61.9 percentage of participants	61.8 percentage of participants
Percentage of Participants With Abdominal Pain (AP) Improvement Through Week 52 Week 52	62.4 percentage of participants	64.9 percentage of participants

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 24, 32, 40, 48, and 52

Population: FAS among participants with mean daily stool frequency \>1 at Baseline.

Number of participants with reduction in frequency of diarrhea were reported. Reduction in frequency of diarrhea was defined as a reduction of at least 3 (or a mean number \<1) in SF (that is, mean daily number of liquid or very soft stools from CDAI score \[ranges from 0 to 3 where higher score indicates severity of pain\] in the week prior to the visit) from baseline, among subjects with mean SF \>1 at baseline, compared at each visit through Week 52.

Outcome measures

Outcome measures
Measure	Adalimumab n=186 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=179 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 2	33.3 percentage of participants	30.7 percentage of participants
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 8	52.7 percentage of participants	60.3 percentage of participants
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 16	53.8 percentage of participants	60.9 percentage of participants
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 24	58.1 percentage of participants	60.9 percentage of participants
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 32	58.1 percentage of participants	60.9 percentage of participants
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 40	54.8 percentage of participants	64.2 percentage of participants
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 48	53.8 percentage of participants	57.5 percentage of participants
Percentage of Participants With Reduction in Frequency of Diarrhea Through Week 52 Week 52	52.7 percentage of participants	60.3 percentage of participants

SECONDARY outcome

Timeframe: At Weeks 8, 16 and 52

Population: FAS which was defined as all randomized participants.

Percentage of participants with clinical and biomarker remission was defined as the percentage of participants with CDAI \<150, CRP \<= 3 mg/L, and also fecal calprotectin \<=250 micrograms per gram (mcg/g). The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. A decrease in CDAI over time indicates improvement in disease activity.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Clinical and Biomarker Remission at Weeks 8, 16 and 52 Week 8	19.5 percentage of participants	14.1 percentage of participants
Percentage of Participants With Clinical and Biomarker Remission at Weeks 8, 16 and 52 Week 16	29.7 percentage of participants	18.8 percentage of participants
Percentage of Participants With Clinical and Biomarker Remission at Weeks 8, 16 and 52 Week 52	27.2 percentage of participants	20.9 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52 and up to Week 76

Population: Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.

Percentage of participants with AE were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Adverse Events (AEs) Up to Week 76	80.0 percentage of participants	81.7 percentage of participants
Percentage of Participants With Adverse Events (AEs) Up to Week 52	77.9 percentage of participants	80.1 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52 and up to Week 76

Population: Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.

Percentage of participants with infections were reported.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Infections Up to Week 52	40.5 percentage of participants	34.0 percentage of participants
Percentage of Participants With Infections Up to Week 76	43.1 percentage of participants	37.2 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52 and up to Week 76

Population: Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.

Percentage of participants with serious infections were reported.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Serious Infections Up to Week 52	2.6 percentage of participants	2.1 percentage of participants
Percentage of Participants With Serious Infections Up to Week 76	3.1 percentage of participants	3.7 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52 and up to Week 76

Population: Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.

Percentage of participants with SAEs were reported. A SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Coronavirus disease 2019 (COVID-19) related adverse events are adverse events with any of the following preferred terms "COVID-19", "Asymptomatic COVID-19", "Suspected COVID-19", "COVID-19 pneumonia", "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positive" or with a reported term containing the string "COVI.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Serious Adverse Events (SAEs) Up to Week 52	16.4 percentage of participants	13.1 percentage of participants
Percentage of Participants With Serious Adverse Events (SAEs) Up to Week 52: COVID-19 related SAEs	0 percentage of participants	0 percentage of participants
Percentage of Participants With Serious Adverse Events (SAEs) Up to Week 76	19.5 percentage of participants	15.2 percentage of participants
Percentage of Participants With Serious Adverse Events (SAEs) Up to Week 76: COVID-19 related SAEs	0 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: Immunogenicity analysis set included all participants who had received at least 1 administration of study agent and have at least one valid blood sample drawn for detection of antibodies to study agent.

Percentage of participants with anti-drug antibodies were reported. Serum samples were assessed for anti-drug antibodies. Anti-drug assays were performed for ustekinumab and adalimumab.

Outcome measures

Outcome measures
Measure	Adalimumab n=195 Participants Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=190 Participants Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Percentage of Participants With Anti-drug Antibodies	74.4 percentage of participants	2.1 percentage of participants

Adverse Events

Adalimumab

Serious events: 38 serious events

Other events: 151 other events

Deaths: 1 deaths

Ustekinumab

Serious events: 29 serious events

Other events: 152 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

DIRECTOR MEDICAL AFFAIRS MD

Janssen Scientific Affairs, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Adalimumab n=195 participants at risk Participants received intravenous (IV) infusion of placebo for ustekinumab and 4 subcutaneous (SC) injections of adalimumab (each 40 milligrams \[mg\], total dose 160 mg) at Week 0, followed by 2 SC injections of adalimumab (each 40 mg, total dose 80 mg) at Week 2. From Week 4 to Week 56, participants self-administered 1 SC injection of adalimumab 40 mg every 2 weeks (q2w).	Ustekinumab n=191 participants at risk Participants received IV infusion of ustekinumab (approximately 6 milligram/kilogram \[mg/kg\]) and 4 SC injections of placebo for adalimumab at Week 0, followed by 2 SC injections of placebo at Week 2. From Week 4 to Week 56, participants self-administered one SC injection of ustekinumab 90 mg every 8 weeks (q8w) starting at Week 8 and placebo adalimumab at the other designated q2w dosing intervals.
Blood and lymphatic system disorders Anaemia	1.0% 2/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Blood and lymphatic system disorders Lymphadenopathy	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Cardiac disorders Angina Unstable	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Congenital, familial and genetic disorders Venolymphatic Malformation	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Abdominal Pain	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Anal Fistula	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Crohn's Disease	8.7% 17/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	2.6% 5/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Duodenal Stenosis	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	1.0% 2/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Enterocolitis	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Ileal Stenosis	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	1.0% 2/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	1.0% 2/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Intestinal Perforation	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Intestinal Stenosis	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Intussusception	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Large Intestinal Obstruction	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Large Intestine Perforation	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	1.6% 3/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Gastrointestinal disorders Subileus	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
General disorders Non-Cardiac Chest Pain	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
General disorders Sudden Death	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Hepatobiliary disorders Bile Duct Stone	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Hepatobiliary disorders Cholecystitis Chronic	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Hepatobiliary disorders Jaundice	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Abdominal Abscess	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Anal Abscess	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Appendicitis	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations COVID-19	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Clostridium Difficile Infection	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Diverticulitis	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Epididymitis	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Paracoccidioides Infection	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Pneumonia	1.0% 2/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Pulmonary Tuberculosis	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Rectal Abscess	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Infections and infestations Urinary Tract Infection	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Injury, poisoning and procedural complications Crush Injury	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Injury, poisoning and procedural complications Thoracic Vertebral Fracture	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Metabolism and nutrition disorders Malnutrition	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Musculoskeletal and connective tissue disorders Foot Deformity	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Nervous system disorders Dizziness Postural	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Nervous system disorders Epilepsy	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Nervous system disorders Migraine	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Psychiatric disorders Psychotic Disorder	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Reproductive system and breast disorders Ovarian Cyst	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Skin and subcutaneous tissue disorders Psoriasis	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Vascular disorders Peripheral Vascular Disorder	0.00% 0/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.52% 1/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.
Vascular disorders Thrombophlebitis	0.51% 1/195 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.	0.00% 0/191 • Up to 81 weeks Safety analysis set included all the participants who were randomized and received at least one administration of study agent in the study.