Trial Outcomes & Findings for A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF) Inhibitors (NCT NCT02171429)

Last Updated: 2021-07-23

Results Overview

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

358 participants

Primary outcome timeframe

Week 10

Results posted on

2021-07-23

Participant Flow

Participants who were on concomitant background therapy were allowed to continue receiving stable baseline doses of the following non-investigational medicinal products during the study: oral 5-aminosalicylic acid; azathioprine; 6-mercaptopurine; methotrexate; corticosteroids up to 30 mg/day of prednisone (or equivalent); and/or budesonide up to 9 mg/day.

Participant milestones

Participant milestones
Measure	Placebo The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Adalimumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive adalimumab subcutaneously (SC) Q2W up to Week 8 (160 mg at Week 0 \[Day 1\], 80 mg at Week 2, 40 mg at Weeks 4, 6, and 8) and placebo matching to etrolizumab SC Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Overall Study STARTED	72	143	143
Overall Study Completed Week 10 Visit	70	141	141
Overall Study COMPLETED	71	140	138
Overall Study NOT COMPLETED	1	3	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Adalimumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive adalimumab subcutaneously (SC) Q2W up to Week 8 (160 mg at Week 0 \[Day 1\], 80 mg at Week 2, 40 mg at Weeks 4, 6, and 8) and placebo matching to etrolizumab SC Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Overall Study Other	0	1	1
Overall Study Non-Compliance	0	0	1
Overall Study Physician Decision	0	0	1
Overall Study Withdrawal by Subject	1	1	1
Overall Study Lost to Follow-up	0	1	0
Overall Study Death	0	0	1

Baseline Characteristics

Baseline characteristics are presented for two populations: all 358 participants enrolled in this study, GA28949 (NCT02171429); and a total pooled population of 716 participants, which consists of all 358 participants from this study (GA28949) plus all 358 participants enrolled in a second study of identical design, GA28948 (NCT02163759).

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Week 10

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Placebo, as Determined by the Mayo Clinic Score (MCS), GA28949 Population	11.1 Percentage of participants Interval 5.74 to 20.42	18.2 Percentage of participants Interval 12.72 to 25.31	—

SECONDARY outcome

Timeframe: Week 10

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10). The Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.

Outcome measures

Outcome measures
Measure	Placebo n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants in Remission at Week 10 With Etrolizumab Compared With Adalimumab, as Determined by the MCS, GA28949 Population	24.5 Percentage of participants Interval 18.16 to 32.13	18.2 Percentage of participants Interval 12.72 to 25.31	—

SECONDARY outcome

Timeframe: Week 10

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10). The Cochran-Mantel-Haenszel test adjusted the difference in remission rates and associated 95% confidence interval for the stratification factors.

Outcome measures

Outcome measures
Measure	Placebo n=285 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=287 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants in Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population	23.5 Percentage of participants Interval 18.96 to 28.76	18.8 Percentage of participants Interval 14.72 to 23.74	—

SECONDARY outcome

Timeframe: Week 10

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Clinical Response was defined as: MCS ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Non-responders also included participants with missing Week 10 assessments or those who had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9 or ≥10); the CMH test adjusted the differences in response rates and associated 95% CIs for the stratification factors.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants With Clinical Response at Week 10, as Determined by the MCS, GA28949 Population	38.9 Percentage of participants Interval 28.47 to 50.44	54.5 Percentage of participants Interval 46.37 to 62.48	52.4 Percentage of participants Interval 44.31 to 60.46

SECONDARY outcome

Timeframe: Week 10

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Clinical Response was defined as: MCS ≥3-point decrease and 30% reduction from baseline as well as ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1. Non-responders also included participants with missing Week 10 assessments or those who had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9 or ≥10); the CMH test adjusted the differences in response rates and associated 95% CIs for the stratification factors.

Outcome measures

Outcome measures
Measure	Placebo n=285 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=287 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants With Clinical Response at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS, GA28948 & GA28949 Pooled Population	53.3 Percentage of participants Interval 47.54 to 59.04	54.7 Percentage of participants Interval 48.92 to 60.36	—

SECONDARY outcome

Timeframe: Week 10

Improvement in endoscopic appearance of the mucosa was defined as a Mayo Clinic Score (MCS) endoscopy subscore ≤1. Blinded gastroenterologists experienced in inflammatory bowel disease performed central reading of endoscopies at an independent review facility. The rectum, sigmoid, and descending colon segments were assessed and each segment was assigned a score of 0 to 3, with higher scores indicating more severe disease. At baseline all segments were reviewed and the worst score from the three segments was recorded as the endoscopy subscore. Post-baseline the endoscopy score was the worst score of all segments that had been assessed at baseline, if the baseline endoscopy score had a sigmoid colon score ≤1. If at baseline the sigmoid colon score was ≥2, the post-baseline endoscopy score was the sigmoid colon score value. Non-responders also included participants with missing Week 10 assessments or those who had received permitted/prohibited rescue therapy prior to assessment.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10, as Determined by the Mayo Endoscopy Subscore, GA28949 Population	30.6 Percentage of participants Interval 21.13 to 41.95	42.7 Percentage of participants Interval 34.85 to 50.85	39.9 Percentage of participants Interval 32.2 to 48.05

SECONDARY outcome

Timeframe: Week 10

Outcome measures

Outcome measures
Measure	Placebo n=285 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=287 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants With Improvement in Endoscopic Appearance of the Mucosa at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population	37.9 Percentage of participants Interval 32.46 to 43.65	40.1 Percentage of participants Interval 34.57 to 45.83	—

SECONDARY outcome

Timeframe: Week 10

Endoscopic remission was defined as a Mayo Clinic Score (MCS) endoscopy subscore of 0. Blinded gastroenterologists experienced in inflammatory bowel disease performed central reading of endoscopies at an independent review facility. The rectum, sigmoid, and descending colon segments were assessed and each segment was assigned a score of 0 to 3, with higher scores indicating more severe disease. At baseline all segments were reviewed and the worst score from the three segments was recorded as the endoscopy subscore. Post-baseline the endoscopy score was the worst score of all segments that had been assessed at baseline, if the baseline endoscopy score had a sigmoid colon score ≤1. If at baseline the sigmoid colon score was ≥2, the post-baseline endoscopy score was the sigmoid colon score value. Non-responders also included participants with missing Week 10 assessments or those who had received permitted/prohibited rescue therapy prior to assessment.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants in Endoscopic Remission at Week 10, as Determined by the MCS Endoscopy Subscore, GA28949 Population	8.3 Percentage of participants Interval 3.88 to 17.01	26.6 Percentage of participants Interval 20.02 to 34.36	19.6 Percentage of participants Interval 13.91 to 26.84

SECONDARY outcome

Timeframe: Week 10

Outcome measures

Outcome measures
Measure	Placebo n=285 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=287 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants in Endoscopic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the MCS Endoscopy Subscore, GA28948 & GA28949 Pooled Population	23.5 Percentage of participants Interval 18.96 to 28.76	20.2 Percentage of participants Interval 15.97 to 25.23	—

SECONDARY outcome

Timeframe: Week 10

Population: GA28949 Histology-Evaluable Population: included all randomized participants in study GA28949 who received at least one dose of study drug and had documented neutrophilic inflammation (i.e., NHI \>1) at baseline. This excludes participants who had no baseline histology assessment or had no indication of neutrophilic inflammation at baseline.

Histologic remission is defined by the resolution of neutrophilic inflammation (e.g., absence of neutrophils in the crypts and lamina propria), defined by a Nancy Histological Index (NHI) score of ≤1. The NHI score ranges from 0 to 4, with the following definitions for each grade: 0 is no histologically significant disease; 1 is chronic inflammatory infiltrate with no acute inflammatory infiltrate; and 2, 3, and 4 are mildly, moderately, and severely active disease, respectively. A small pool of central readers who were blinded to both treatment arm and timepoint performed the histologic scoring. The same reader scored all slides for a given participant based on biopsies from the most inflamed region of the sigmoid colon. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received rescue therapy prior to assessment. The Cochran-Mantel-Haenszel test adjusted the difference in remission rates and 95% CI for the stratification factors.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=114 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=108 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants With Histologic Remission at Week 10, as Determined by the Nancy Histological Index, GA28949 Population	21.0 Percentage of participants Interval 12.68 to 32.64	43.9 Percentage of participants Interval 35.1 to 53.02	30.6 Percentage of participants Interval 22.66 to 39.79

SECONDARY outcome

Timeframe: Week 10

Population: GA28948 \& GA28949 Pooled, Histology-Evaluable Population: included all randomized participants in studies GA28948 \& GA28949 who received at least one dose of study drug and had documented neutrophilic inflammation (i.e., NHI \>1) at baseline. This excludes participants who had no baseline histology assessment or had no indication of neutrophilic inflammation at baseline.

Outcome measures

Outcome measures
Measure	Placebo n=230 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=228 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants With Histologic Remission at Week 10 With Etrolizumab as Compared With Adalimumab, as Determined by the Nancy Histological Index, GA28948 & GA28949 Pooled Population	36.5 Percentage of participants Interval 30.57 to 42.92	36.8 Percentage of participants Interval 30.85 to 43.27	—

SECONDARY outcome

Timeframe: Baseline, Week 6

Rectal bleeding data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = no blood in the stool; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; 3 = blood alone passed. The Mayo Clinic Score (MCS) rectal bleeding subscore was calculated as the worst value of three days of daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline rectal bleeding (RB) subscore.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6, GA28949 Population	0.0 Score on a scale Interval -1.0 to 0.0	-1.0 Score on a scale Interval -2.0 to 0.0	-1.0 Score on a scale Interval -2.0 to 0.0

SECONDARY outcome

Timeframe: Baseline, Week 6

Outcome measures

Outcome measures
Measure	Placebo n=285 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=287 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in the MCS Rectal Bleeding Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population	-1.0 Score on a scale Interval -2.0 to 0.0	-1.0 Score on a scale Interval -2.0 to 0.0	—

SECONDARY outcome

Timeframe: Baseline, Week 6

Stool frequency data were collected via the participant's diaries and each day a participant provided a score from 0 to 3 according to the following definitions: 0 = normal number of stools; 1 = 1 to 2 more stools than normal; 2 = 3 to 4 more stools than normal; 3 = 5 or more stools than normal. The Mayo Clinic Score (MCS) stool frequency subscore was calculated as the average of three days daily diary scores closest to anchor dates at baseline and post-baseline. The data was considered non-parametric and was reported using RANK analysis of covariance (ANCOVA). Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10); the model adjusted for these stratification factors along with the baseline stool frequency (SF) subscore.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in the MCS Stool Frequency Subscore at Week 6, GA28949 Population	0.0 Score on a scale Interval -1.0 to 0.0	-1.0 Score on a scale Interval -1.0 to 0.0	-1.0 Score on a scale Interval -1.0 to 0.0

SECONDARY outcome

Timeframe: Baseline, Week 6

Outcome measures

Outcome measures
Measure	Placebo n=285 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=287 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in the MCS Stool Frequency Subscore at Week 6 With Etrolizumab as Compared With Adalimumab, GA28948 & GA28949 Pooled Population	-1.0 Score on a scale Interval -1.0 to 0.0	-1.0 Score on a scale Interval -1.0 to 0.0	—

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: GA28949 Population, Modified Intent-to-Treat: including all randomized participants in study GA28949 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization. The analysis only included participants with non-missing results at baseline and at least one post-baseline timepoint.

The UC-PRO/SS questionnaire was collected in the e-diary and completed by participants for at least 9 to 12 consecutive days prior to a study visit. The bowel movement domain score ranges from 0 to 27, with a higher score indicating a worse disease state. The most recent 7 daily scores available (not including the visit) were selected for the calculation of the visit score. For each item in the questionnaire, a score was calculated for a visit by taking the average of the selected daily scores. The domain score for a visit was calculated as the sum of the averaged items for each question. A Mixed Model for Repeated Measures (MMRM) analysis of the data included the fixed categorical effects of treatment, visit, study stratification factors, and treatment-by-visit interaction, and the continuous covariates of the baseline UC-PRO/SS domain and baseline UC-PRO/SS domain-by-visit interaction. An unstructured covariance matrix was used to model the within-patient errors within the MMRM.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=111 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=108 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in Ulcerative Colitis (UC) Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC Patient-Reported Outcome Signs and Symptoms (UC-PRO/SS), GA28949 Population	-4.7 Score on a scale Standard Error 0.7	-5.9 Score on a scale Standard Error 0.5	-5.8 Score on a scale Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline, Week 10

Population: GA28948 \& GA28949 Pooled Population, Modified Intent-to-Treat: including all randomized participants in studies GA28948 \& GA28949 who received at least one dose of study drug, with participants grouped according to the treatment assigned at randomization. The analysis only included participants with non-missing results at baseline and at least one post-baseline timepoint.

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=217 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=225 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in Ulcerative Colitis Bowel Movement Signs and Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population	-5.0 Score on a scale Standard Error 0.5	-5.8 Score on a scale Standard Error 0.4	-6.0 Score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline, Week 10

The UC-PRO/SS questionnaire was collected in the e-diary and completed by participants for at least 9 to 12 consecutive days prior to a study visit. The functional symptoms domain score ranges from 0 to 12, with a higher score indicating a worse disease state. The most recent 7 daily scores available (not including the visit) were selected for the calculation of the visit score. For each item in the questionnaire, a score was calculated for a visit by taking the average of the selected daily scores. The domain score for a visit was calculated as the sum of the averaged items for each question. A Mixed Model for Repeated Measures (MMRM) analysis of the data included the fixed categorical effects of treatment, visit, study stratification factors, and treatment-by-visit interaction, and the continuous covariates of the baseline UC-PRO/SS domain and baseline UC-PRO/SS domain-by-visit interaction. An unstructured covariance matrix was used to model the within-patient errors in the MMRM.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=111 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=108 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28949 Population	-1.0 Score on a scale Standard Error 0.3	-1.8 Score on a scale Standard Error 0.2	-2.0 Score on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline, Week 10

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=217 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=225 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in Ulcerative Colitis Functional Symptoms at Week 10, as Assessed by the UC-PRO/SS, GA28948 & GA28949 Pooled Population	-1.4 Score on a scale Standard Error 0.2	-1.6 Score on a scale Standard Error 0.2	-1.9 Score on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Week 10

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Clinical remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1. Participants were also classified as non-remitters if Week 10 assessments were missing or if they had received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10). The Cochran-Mantel-Haenszel test adjusted the differences in remission rates and associated 95% confidence intervals for the stratification factors.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants in Clinical Remission at Week 10, as Determined by the MCS, GA28949 Population	11.1 Percentage of participants Interval 5.74 to 20.42	25.9 Percentage of participants Interval 19.39 to 33.62	18.9 Percentage of participants Interval 13.31 to 26.08

SECONDARY outcome

Timeframe: Weeks 10 and 14

The Mayo Clinic Score (MCS) ranges from 0 to 12 and is a composite of the four following assessments of disease activity: stool frequency subscore, rectal bleeding subscore, endoscopy subscore, and physician's global assessment (PGA) subscore. Each of the four assessments was rated with a score from 0 to 3, with higher scores indicating more severe disease. Remission was defined as MCS less than or equal to (≤)2 with individual subscores ≤1 and a rectal bleeding subscore of 0. Participants were also classified as non-remitters if Week 10 or 14 assessments were missing or the participant received permitted/prohibited rescue therapy prior to assessment. Participants were stratified by concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening (MCS ≤9/MCS ≥10). The Cochran-Mantel-Haenszel test adjusted the differences in remission rates and associated 95% confidence intervals for the stratification factors.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Percentage of Participants in Remission at Week 10 and Week 14, as Determined by the MCS, GA28949 Population	6.9 Percentage of participants Interval 3.0 to 15.25	14.7 Percentage of participants Interval 9.81 to 21.41	9.8 Percentage of participants Interval 5.92 to 15.76

SECONDARY outcome

Timeframe: Baseline, Week 10

The IBDQ is a 32-item questionnaire containing four domains: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). An overall total IBDQ score was computed by summing the individual 32-item scores. The range for the IBDQ total score is 32 to 224, with higher scores denoting better health-related quality of life. The unadjusted mean and standard deviation for each study arm are reported. The change from baseline in the IBDQ score was analyzed using an ANCOVA model taking the stratification factors used at randomization into account (concomitant treatment with corticosteroids or immunosuppressants at randomization and disease activity measured during screening \[MCS ≤9/MCS ≥10\]), and the baseline IBDQ score used as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=125 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=125 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Change From Baseline in Health-Related Quality of Life at Week 10, as Assessed by the Total Inflammatory Bowel Disease Questionnaire (IBDQ) Score, GA28949 Population	31.2 Score on a scale Standard Deviation 39.5	34.8 Score on a scale Standard Deviation 36.5	36.2 Score on a scale Standard Deviation 43.4

SECONDARY outcome

Timeframe: Weeks 10 and 14

Population: GA28949 Pharmacokinetics Evaluable Population: includes participants in study GA28949 who had received at least one dose of study drug and had at least one quantifiable concentration measured post-baseline. Only participants who were treated with etrolizumab were included in this analysis.

Serum concentrations of etrolizumab were evaluated at the primary endpoint visit (Week 10) and the secondary endpoint visit (Week 14). Both time points were two weeks after the most recent dose.

Outcome measures

Outcome measures
Measure	Placebo n=139 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Pharmacokinetics of Etrolizumab: Serum Concentration, GA28949 Population Week 10	12.4 micrograms per millilitre (μg/mL) Standard Deviation 5.51	—	—
Pharmacokinetics of Etrolizumab: Serum Concentration, GA28949 Population Week 14	15.5 micrograms per millilitre (μg/mL) Standard Deviation 6.49	—	—

SECONDARY outcome

Timeframe: From Baseline until the end of study (up to 26 weeks)

Population: GA28949 Safety Population: includes all participants in study GA28949 who received at least one dose of study drug, with participants grouped according to the treatment received.

An adverse event (AE) is any untoward medical occurrence in a clinical investigation in which a patient is administered a pharmaceutical product, regardless of causal attribution. The investigator independently assessed the severity and seriousness of each recorded AE. The AE severity grading scale for the NCI CTCAE v4.0 was used for assessing severity; any AE not specifically listed was rated according to the following grading scale from 1 to 5: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death. AEs of special interest included: elevated AST/ALT in combination with either elevated bilirubin or clinical jaundice; suspected transmission of infectious agent by the study drug; anaphylactic, anaphylactoid and systemic hypersensitivity reactions; and neurological signs, symptoms, and AEs that may suggest possible progressive multifocal leukoencephalopathy (PML).

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Any Adverse Event (AE)	33 Participants	62 Participants	63 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE with Fatal Outcome	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Serious AE	5 Participants	3 Participants	7 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE Leading to Study Treatment Discontinuation	1 Participants	2 Participants	4 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE Leading to Dose Interruption	0 Participants	2 Participants	1 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Related AE	9 Participants	15 Participants	12 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE by Worst Severity, Grade 1	14 Participants	29 Participants	30 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE by Worst Severity, Grade 2	13 Participants	25 Participants	24 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE by Worst Severity, Grade 3	6 Participants	8 Participants	8 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE by Worst Severity, Grade 4	0 Participants	0 Participants	0 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AE by Worst Severity, Grade 5	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Any AEs of Special Interest (AESIs), Except for Hypersensitivity Reactions	0 Participants	0 Participants	0 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population AESIs: Anaphylactic, Anaphylactoid, and Systemic Hypersensitivity Reactions	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Confirmed PML	0 Participants	0 Participants	0 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Infections	13 Participants	18 Participants	23 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Serious Infections	0 Participants	1 Participants	2 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Gastrointestinal Infections	1 Participants	0 Participants	3 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Opportunistic Infections	0 Participants	0 Participants	0 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Malignancies	0 Participants	2 Participants	0 Participants
Number and Percentage of Participants With at Least One Adverse Event by Severity, According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), GA28949 Population Injection Site Reactions	2 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: From Baseline up to Week 10

Population: GA28949 Safety Population: includes all participants in study GA28949 who received at least one dose of study drug, with participants grouped according to the treatment received.

Laboratory tests for hematology parameters were performed and values were compared with the Roche marked reference range. A marked abnormality was defined as a test result that was outside of the Roche marked reference range (labelled as 'High' or 'Low') and represented a clinically significant change from baseline. Not every laboratory abnormality qualified as an adverse event. A laboratory test result must have been reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment or a medical intervention; or was clinically significant in the investigator's judgment. The results are presented as a shift from the baseline status to the post-baseline (Week 10) status. Baseline was defined as the last available assessment prior to first receipt of study drug. The 'missing' status included participants with missing baseline or post-baseline values. Ery. = erythrocyte

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hemoglobin - Normal to Low	4 Participants	4 Participants	7 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hemoglobin - Normal to Normal	56 Participants	113 Participants	99 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hemoglobin - Normal to Missing	5 Participants	6 Participants	10 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hemoglobin - Missing to Normal	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Lymphocytes Abs - Low to Low	2 Participants	2 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Lymphocytes Abs - Low to Normal	2 Participants	9 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Lymphocytes Abs - Low to Missing	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Lymphocytes Abs - Normal to Low	1 Participants	2 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Lymphocytes Abs - Normal to Normal	60 Participants	121 Participants	119 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Lymphocytes Abs - Normal to Missing	7 Participants	9 Participants	14 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Lymphocytes Abs - Missing to Normal	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Ery. Mean Corpuscular Volume - Normal to Low	0 Participants	1 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Ery. Mean Corpuscular Volume - Normal to Normal	65 Participants	130 Participants	126 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Ery. Mean Corpuscular Volume - Normal to Missing	7 Participants	9 Participants	15 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Ery. Mean Corpuscular Volume - High to High	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Ery. Mean Corpuscular Volume - High to Missing	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Ery. Mean Corpuscular Volume - Missing to Normal	0 Participants	1 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Low to Low	1 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Low to Normal	0 Participants	3 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Low to Missing	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Normal to Low	0 Participants	7 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Normal to Normal	55 Participants	105 Participants	105 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Normal to High	1 Participants	1 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Normal to Missing	8 Participants	7 Participants	15 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - High to Normal	3 Participants	15 Participants	7 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - High to High	4 Participants	1 Participants	5 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - High to Missing	0 Participants	2 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Neutrophils, Total, Abs - Missing to Normal	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Platelets - Normal to Normal	59 Participants	128 Participants	116 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Platelets - Normal to High	1 Participants	0 Participants	3 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Platelets - Normal to Missing	9 Participants	9 Participants	15 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Platelets - High to Normal	2 Participants	2 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Platelets - High to High	1 Participants	2 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Platelets - High to Missing	0 Participants	1 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Platelets - Missing to Normal	0 Participants	1 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Low to Low	1 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Low to Normal	0 Participants	4 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Low to Missing	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Normal to Low	0 Participants	3 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Normal to Normal	64 Participants	123 Participants	124 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Normal to High	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Normal to Missing	7 Participants	8 Participants	14 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - High to Normal	0 Participants	2 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population White Blood Cell Count - Missing to Normal	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Eosinophils Absolute Count (Abs) - Normal to Normal	63 Participants	133 Participants	124 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Eosinophils Abs - Normal to High	0 Participants	0 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Eosinophils Abs - Normal to Missing	7 Participants	9 Participants	15 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Eosinophils Abs - High to Normal	2 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Eosinophils Abs - High to High	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Eosinophils Abs - Missing to Normal	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hematocrit - Low to Low	0 Participants	1 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hematocrit - Low to Normal	3 Participants	2 Participants	5 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hematocrit - Low to Missing	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hematocrit - Normal to Low	0 Participants	1 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hematocrit - Normal to Normal	62 Participants	128 Participants	119 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hematocrit - Normal to Missing	7 Participants	10 Participants	14 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hematocrit - Missing to Normal	0 Participants	1 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hemoglobin - Low to Low	3 Participants	10 Participants	13 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hemoglobin - Low to Normal	2 Participants	7 Participants	9 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Hematology Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Hemoglobin - Low to Missing	2 Participants	3 Participants	4 Participants

SECONDARY outcome

Timeframe: From Baseline up to Week 10

Population: GA28949 Safety Population: includes all participants in study GA28949 who received at least one dose of study drug, with participants grouped according to the treatment received.

Laboratory tests for chemistry parameters were performed and values were compared with the Roche marked reference range. A marked abnormality was defined as a test result that was outside of the Roche marked reference range (labelled as 'High' or 'Low') and represented a clinically significant change from baseline. Not every laboratory abnormality qualified as an adverse event. A laboratory test result must have been reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment or a medical intervention; or was clinically significant in the investigator's judgment. The results are presented as a shift from the baseline status to the post-baseline (Week 10) status. Baseline was defined as the last available assessment prior to first receipt of study drug. The 'missing' status included participants with missing baseline or post-baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab n=143 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Albumin - Low to Normal	2 Participants	3 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Albumin - Low to Missing	0 Participants	0 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Albumin - Normal to Low	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Albumin - Normal to Normal	65 Participants	134 Participants	137 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Albumin - Normal to Missing	5 Participants	5 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alkaline Phosphatase - Normal to Normal	67 Participants	138 Participants	137 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alkaline Phosphatase - High to Normal	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alanine Aminotransferase - High to Normal	1 Participants	1 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Aspartate Aminotransferase - Normal to High	0 Participants	0 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Aspartate Aminotransferase - Normal to Missing	6 Participants	8 Participants	5 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Aspartate Aminotransferase - High to Normal	1 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - Normal to Low	6 Participants	9 Participants	10 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - Normal to Normal	55 Participants	121 Participants	116 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - Normal to Missing	5 Participants	7 Participants	3 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - High to High	0 Participants	2 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - High to Missing	0 Participants	0 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alkaline Phosphatase - Normal to Missing	5 Participants	5 Participants	5 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alanine Aminotransferase - Normal to Normal	65 Participants	134 Participants	134 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alanine Aminotransferase - Normal to High	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alanine Aminotransferase - Normal to Missing	6 Participants	7 Participants	5 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Alanine Aminotransferase - High to High	0 Participants	0 Participants	2 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Aspartate Aminotransferase - Normal to Normal	65 Participants	135 Participants	135 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - Low to Low	1 Participants	0 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - Low to Normal	1 Participants	3 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - Normal to High	0 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Bicarbonate (CO2) - High to Normal	4 Participants	1 Participants	10 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Blood Urea Nitrogen - Normal to Normal	67 Participants	138 Participants	139 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Blood Urea Nitrogen - Normal to Missing	5 Participants	5 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Calcium - Normal to Normal	67 Participants	138 Participants	139 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Calcium - Normal to Missing	5 Participants	5 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Chloride - Low to Low	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Chloride - Low to Missing	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Chloride - Normal to Low	1 Participants	1 Participants	3 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Chloride - Normal to Normal	66 Participants	135 Participants	136 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Chloride - Normal to Missing	5 Participants	5 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Creatinine - Normal to Normal	67 Participants	138 Participants	139 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Creatinine - Normal to Missing	5 Participants	5 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Direct Bilirubin - Normal to Normal	66 Participants	132 Participants	137 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Direct Bilirubin - Normal to Missing	6 Participants	10 Participants	6 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Direct Bilirubin - Missing to Normal	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Potassium - Normal to Low	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Potassium - Normal to Normal	66 Participants	135 Participants	137 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Potassium - Normal to Missing	6 Participants	7 Participants	6 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Sodium - Normal to Normal	67 Participants	137 Participants	139 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Sodium - Normal to Missing	5 Participants	6 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Total Bilirubin - Normal to Normal	66 Participants	135 Participants	136 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Total Bilirubin - Normal to High	1 Participants	3 Participants	3 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Total Bilirubin - Normal to Missing	5 Participants	5 Participants	4 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Protein, Total - Low to Normal	1 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Protein, Total - Normal to Low	0 Participants	1 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Protein, Total - Normal to Normal	64 Participants	132 Participants	135 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Protein, Total - Normal to High	1 Participants	5 Participants	0 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Protein, Total - Normal to Missing	5 Participants	5 Participants	5 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Protein, Total - High to Normal	1 Participants	0 Participants	1 Participants
Number and Percentage of Participants by Marked Laboratory Abnormality Status for Chemistry Parameters as a Shift Table From Baseline to Week 10, GA28949 Population Protein, Total - High to High	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Pre-dose (0 hour) on Day 1 and Week 4, Week 10, Week 14, and early termination/end of safety follow-up (up to 26 weeks)

Population: GA28949 Safety Population: includes all participants in study GA28949 who received at least one dose of study drug, with participants grouped according to the treatment received. The analysis of ADAs at baseline and post-baseline only included participants who received treatment with etrolizumab.

Anti-drug antibody (ADA) serum samples were collected from participants and analyzed using validated assays. Participants were considered to be ADA positive post-baseline if they were ADA negative or had missing data at baseline, but developed an ADA response following etrolizumab drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were ADA negative or had missing data at baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 titer unit greater than the titer of the baseline sample (treatment unaffected).

Outcome measures

Outcome measures
Measure	Placebo n=141 Participants The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Etrolizumab The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population Positive for ADAs at Baseline (BL)	7 Participants	—	—
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population Post-BL ADA Positive: Treatment-Enhanced ADAs	0 Participants	—	—
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population Post-BL: Negative for Treatment Emergent ADAs	115 Participants	—	—
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population Negative for ADAs at BL	134 Participants	—	—
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population Post-BL: Positive for Treatment Emergent ADAs	26 Participants	—	—
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population Post-BL ADA Positive: Treatment-Induced ADAs	26 Participants	—	—
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Anytime Post-Baseline, GA28949 Population Post-BL ADA Negative: Treatment Unaffected	7 Participants	—	—

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Adalimumab

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Etrolizumab

Serious events: 7 serious events

Other events: 20 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=72 participants at risk The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Adalimumab n=143 participants at risk The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive adalimumab subcutaneously (SC) Q2W up to Week 8 (160 mg at Week 0 \[Day 1\], 80 mg at Week 2, 40 mg at Weeks 4, 6, and 8) and placebo matching to etrolizumab SC Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).	Etrolizumab n=143 participants at risk The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Eye disorders Visual impairment	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Gastrointestinal disorders Colitis ulcerative	2.8% 2/72 • Number of events 2 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Gastrointestinal disorders Colon dysplasia	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Gastrointestinal disorders Pancreatitis acute	1.4% 1/72 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Gastrointestinal disorders Proctitis	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
General disorders Sudden cardiac death	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Infections and infestations Clostridium difficile infection	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Infections and infestations Pulpitis dental	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Infections and infestations Urinary tract infection	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anaplastic oligodendroglioma	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.70% 1/143 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/72 • Number of events 1 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Vascular disorders Deep vein thrombosis	2.8% 2/72 • Number of events 2 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	0.00% 0/143 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.

Other adverse events

Other adverse events
Measure	Placebo n=72 participants at risk The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive placebo matching to etrolizumab subcutaneously (SC) once every 4 weeks (Q4W) up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC once every 2 weeks (Q2W) up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).	Adalimumab n=143 participants at risk The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive adalimumab subcutaneously (SC) Q2W up to Week 8 (160 mg at Week 0 \[Day 1\], 80 mg at Week 2, 40 mg at Weeks 4, 6, and 8) and placebo matching to etrolizumab SC Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]).	Etrolizumab n=143 participants at risk The double-blinded treatment period consisted of a 10-week induction period and an additional 4-week treatment period for participants who met the definition of clinical remission at Week 10. Participants with moderate-to-severe ulcerative colitis who were naive to TNF inhibitors were randomized to this arm to receive etrolizumab 105 mg subcutaneously (SC) Q4W up to Week 12 (at Weeks 0 \[Day 1\], 4, 8, and 12 \[clinical remitters only\]) and placebo matching to adalimumab SC Q2W up to Week 8 (at Weeks 0 \[Day 1\], 2, 4, 6, and 8).
Blood and lymphatic system disorders Anaemia	6.9% 5/72 • Number of events 5 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	1.4% 2/143 • Number of events 2 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	3.5% 5/143 • Number of events 5 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Gastrointestinal disorders Colitis ulcerative	11.1% 8/72 • Number of events 8 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	8.4% 12/143 • Number of events 12 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	7.7% 11/143 • Number of events 11 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Infections and infestations Upper respiratory tract infection	5.6% 4/72 • Number of events 5 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	2.1% 3/143 • Number of events 4 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	2.8% 4/143 • Number of events 4 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.
Nervous system disorders Headache	0.00% 0/72 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	6.3% 9/143 • Number of events 10 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.	2.1% 3/143 • Number of events 3 • From Baseline until the end of study (up to 26 weeks) The adverse events reported here are those that occurred only in participants enrolled in study GA28949 who received at least one dose of study drug. For the adverse events that occurred in participants enrolled in the identically designed study, GA28948, please refer to its study record, NCT02163759.

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