Trial Outcomes & Findings for Certolizumab Pegol for the Treatment of Patients With Active Rheumatoid Arthritis (NCT NCT00717236)

Last Updated: 2018-08-01

Results Overview

ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1648 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2018-08-01

Participant Flow

The study started in July 2008 with subjects from the United States, Canada, France, Germany, Italy, the Netherlands, and Spain. The primary completion date occurred in March 2010, with study completion in March 2011.

Of the 1648 subjects that were screened, 585 subjects had screen failures. Therefore, 1063 subjects were randomized in this study.

Participant milestones

Participant milestones
Measure	Certolizumab Pegol (CZP) 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Double-Blind Period STARTED	851	212
Double-Blind Period COMPLETED	771	184
Double-Blind Period NOT COMPLETED	80	28
Open-Label Period STARTED	771	184
Open-Label Period COMPLETED	646	163
Open-Label Period NOT COMPLETED	125	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Certolizumab Pegol (CZP) 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Double-Blind Period Adverse Event	33	6
Double-Blind Period Lack of Efficacy	6	6
Double-Blind Period Lost to Follow-up	3	5
Double-Blind Period Withdrawal by Subject	10	2
Double-Blind Period Loss of efficacy	3	0
Double-Blind Period Other: Death	1	0
Double-Blind Period Other: Pregnancy	1	0
Double-Blind Period Other: Protocol Violation	2	0
Double-Blind Period Other: Inclusion/Exclusion criteria	6	2
Double-Blind Period Other: Site withdrew	2	0
Double-Blind Period Other: Screening failure	1	0
Double-Blind Period Other: subject withdrew consent	1	1
Double-Blind Period Other: Abnormal chest X-ray	2	1
Double-Blind Period Other: History of adenoid grown	1	0
Double-Blind Period Other: History of cancer	1	0
Double-Blind Period Other: Sponsor request	1	0
Double-Blind Period Other: Inappropriate randomization	1	0
Double-Blind Period Other: Detection of Hepatitis C Virus	1	0
Double-Blind Period Other: Subject moved	1	1
Double-Blind Period Other: Stopped taking DMARD	1	0
Double-Blind Period Other: Prohibited medication taken	2	2
Double-Blind Period Other: Transportation problems	0	1
Double-Blind Period Other: Investigator Decision	0	1
Open-Label Period Adverse Event	29	4
Open-Label Period Lack of Efficacy	30	8
Open-Label Period Lost to Follow-up	28	4
Open-Label Period Withdrawal by Subject	20	2
Open-Label Period Loss of Efficacy	6	1
Open-Label Period Other: Peripheral Neuropathy	0	1
Open-Label Period Other: Lack of Compliance	1	1
Open-Label Period Other: History of Basal Cell Carcinoma	1	0
Open-Label Period Other: Moved	1	0
Open-Label Period Other: Investigator Decision	1	0
Open-Label Period Other: Loss of Staff (unblinded)	1	0
Open-Label Period Other: Sponsor Request	3	0
Open-Label Period Other: Cataract Surgery	1	0
Open-Label Period Other: Administration of Golimumab	1	0
Open-Label Period Other: Completion Accidently Performed	1	0
Open-Label Period Other: Medical Monitor Recommendation	1	0

Baseline Characteristics

Certolizumab Pegol for the Treatment of Patients With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Total n=1063 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	644 Participants n=5 Participants	164 Participants n=7 Participants	808 Participants n=5 Participants
Age, Categorical >=65 years	207 Participants n=5 Participants	48 Participants n=7 Participants	255 Participants n=5 Participants
Age, Continuous	55.4 years STANDARD_DEVIATION 12.43 • n=5 Participants	53.9 years STANDARD_DEVIATION 12.66 • n=7 Participants	55.1 years STANDARD_DEVIATION 12.49 • n=5 Participants
Sex: Female, Male Female	660 Participants n=5 Participants	169 Participants n=7 Participants	829 Participants n=5 Participants
Sex: Female, Male Male	191 Participants n=5 Participants	43 Participants n=7 Participants	234 Participants n=5 Participants
Region of Enrollment France	14 participants n=5 Participants	0 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment United States	575 participants n=5 Participants	141 participants n=7 Participants	716 participants n=5 Participants
Region of Enrollment Canada	65 participants n=5 Participants	17 participants n=7 Participants	82 participants n=5 Participants
Region of Enrollment Spain	26 participants n=5 Participants	8 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Netherlands	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Germany	154 participants n=5 Participants	44 participants n=7 Participants	198 participants n=5 Participants
Region of Enrollment Italy	13 participants n=5 Participants	2 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: All 1063 subjects (851 CZP, 212 Placebo) included in the Full Analysis Set (FAS) are included in this analysis

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 12	51.1 percentage of subjects	25.9 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS), 732 were in the concomitant methotrexate use stratum (589 CZP, 143 Placebo) and are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=589 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=143 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use.	52.5 percentage of subjects	28.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS), 331 were in the no concomitant methotrexate use stratum (262 CZP, 69 Placebo) and are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=262 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=69 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use.	48.1 percentage of subjects	21.7 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS), 400 were in the prior anti-tumor necrosis (anti-TNF) use stratum (320 CZP, 80 Placebo) and are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=320 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=80 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use	47.2 percentage of subjects	27.5 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS), 663 were in the no prior anti-tumor necrosis (anti-TNF) use stratum (531 CZP, 132 Placebo) and are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=531 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=132 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use	53.5 percentage of subjects	25.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS), 256 were in the disease duration less than 2 years stratum (206 CZP, 50 Placebo) and are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=206 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=50 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years	50.0 percentage of subjects	30.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS), 807 were in the disease duration greater than or equal to 2 years stratum (645 CZP, 162 Placebo) and are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=645 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=162 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years.	51.5 percentage of subjects	24.7 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.

ACR50 responders are subjects with at least 50% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 50% (ACR50) Response at Week 12	26.6 percentage of subjects	9.9 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.

ACR70 responders are subjects with at least 70% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 70% (ACR70) Response at Week 12.	12.9 percentage of subjects	2.8 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1037(834 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=834 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=203 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12	-1.70 units on a scale Standard Deviation 1.269 • Interval -6.0 to 1.6	-0.84 units on a scale Standard Deviation 1.209 • Interval -4.5 to 2.9

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1024 (824 CZP, 200 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=824 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=200 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12	-19.66 units on a scale Standard Deviation 14.493 • Interval -69.4 to 30.2	-10.78 units on a scale Standard Deviation 15.172 • Interval -47.1 to 52.0

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1024 (824 CZP, 200 Placebo) are included in this analysis.

CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=824 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=200 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12	-18.96 units on a scale Standard Deviation 14.019 • Interval -65.8 to 21.2	-10.93 units on a scale Standard Deviation 14.494 • Interval -47.2 to 43.3

SECONDARY outcome

Timeframe: Week 12

Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12	16.0 percentage of subjects	5.7 percentage of subjects

SECONDARY outcome

Timeframe: Week 12

Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12	7.8 percentage of subjects	1.9 percentage of subjects

SECONDARY outcome

Timeframe: Week 12

Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12	8.3 percentage of subjects	1.9 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1043 (838 CZP, 205 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=838 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=205 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Tender Joint Count (TJC) at Week 12	-7.4 units on a scale Standard Deviation 7.13 • Interval -28.0 to 18.0	-4.5 units on a scale Standard Deviation 7.38 • Interval -28.0 to 12.0

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1043 (838 CZP, 205 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=838 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=205 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Swollen Joint Count (SJC) at Week 12	-6.4 units on a scale Standard Deviation 5.57 • Interval -24.0 to 13.0	-3.6 units on a scale Standard Deviation 5.64 • Interval -21.0 to 21.0

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1029 (826 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=826 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=203 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12	-0.38 units on a scale Standard Deviation 0.524 • Interval -2.4 to 1.8	-0.19 units on a scale Standard Deviation 0.507 • Interval -1.9 to 1.1

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1046 (841 CZP, 205 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from baseline in CRP (mg/L) is computed as the ratio of Week 12 value divided by baseline value. A ratio less then 1 indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=841 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=205 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in C-reactive Protein (CRP) at Week 12	0.55 mg/L Geometric Coefficient of Variation 111.417 • Interval 0.0 to 16.6	1.05 mg/L Geometric Coefficient of Variation 89.633 • Interval 0.1 to 17.6

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1038 (835 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=835 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=203 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12	-22.1 mm Standard Deviation 28.31	-10.7 mm Standard Deviation 27.32

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1038 (835 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=835 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=203 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12	-21.5 mm Standard Deviation 27.78	-10.1 mm Standard Deviation 26.24

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1029 (827 CZP, 202 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=827 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=202 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12	-31.2 mm Standard Deviation 23.58	-19.0 mm Standard Deviation 25.15

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.

The time from randomization to sustained ACR20 response at 2 consecutive visits (at the latest on Week 12).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Time to Sustained American College of Rheumatology 20% (ACR20) Response	40.4 percentage of subjects	13.2 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.

EULAR response (good response, moderate response, or no response) is defined based on the present value and improvement from baseline in DAS28(CRP) \[Disease Activity Score-28 (C-reactive protein)\].

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=212 Participants Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
European League Against Rheumatism (EULAR) Response at Week 12 Good response	28.9 percentage of subjects	10.4 percentage of subjects
European League Against Rheumatism (EULAR) Response at Week 12 Moderate response	44.5 percentage of subjects	37.3 percentage of subjects
European League Against Rheumatism (EULAR) Response at Week 12 No response	26.6 percentage of subjects	52.4 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=954 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 20% (ACR20) Response at Week 28	58.5 percentage of subjects	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=954 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 50% (ACR50) Response at Week 28	35.0 percentage of subjects	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=954 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
American College of Rheumatology 70% (ACR70) Response at Week 28	17.4 percentage of subjects	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 840 had observed values at Week 28 and Baseline and are included in this analysis.

DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=840 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 28	-1.94 units on a scale Standard Error 0.055	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 828 had observed values at Week 28 and Baseline and are included in this analysis.

SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=828 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 28	-22.35 units on a scale Standard Error 0.546	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 840 had observed values at Week 28 and Baseline and are included in this analysis.

CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=840 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 28	-21.66 units on a scale Standard Error 0.533	—

SECONDARY outcome

Timeframe: Week 28

Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=954 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 28	22.6 percentage of subjects	—

SECONDARY outcome

Timeframe: Week 28

Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=954 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 28	11.4 percentage of subjects	—

SECONDARY outcome

Timeframe: Week 28

Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=954 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 28	12.1 percentage of subjects	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 861 had observed values at Week 28 and Baseline and are included in this analysis.

TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=861 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Tender Joint Count (TJC) at Week 28	-8.6 units on a scale Standard Error 0.26	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 861 had observed values at Week 28 and Baseline and are included in this analysis.

SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=861 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Swollen Joint Count (SJC) at Week 28	-7.2 units on a scale Standard Error 0.19	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 854 had observed values at Week 28 and Baseline and are included in this analysis

HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=854 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 28	-0.46 units on a scale Standard Error 0.023	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 851 had observed values at Week 28 and Baseline and are included in this analysis

Change from Baseline in CRP (mg/L) is computed as the ratio of the value at Week 28 divided by Baseline value. A ratio less then 1 indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=851 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in C-reactive Protein (CRP) at Week 28	0.59 mg/L 95% Confidence Interval 122.929 • Interval 0.55 to 0.63	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 856 had observed values at Week 28 and Baseline and are included in this analysis

Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=856 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 28	-23.1 mm Standard Error 1.06	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 857 had observed values at Week 28 and Baseline and are included in this analysis

Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=857 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 28	-23.0 mm Standard Error 1.04	—

SECONDARY outcome

Timeframe: Baseline, Week 28

Population: Of the 954 subjects in the Open Label Set (OLS) 848 had observed values at Week 28 and Baseline and are included in this analysis

Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (CZP) n=848 Participants 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 28	-35.6 mm Standard Error 0.85	—

Adverse Events

Certolizumab Pegol (CZP)

Serious events: 52 serious events

Other events: 174 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 42 other events

Deaths: 0 deaths

Open Label Certolizumab Pegol (CZP)

Serious events: 77 serious events

Other events: 246 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Certolizumab Pegol (CZP) n=846 participants at risk 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. From Week 12, 200 mg CZP given every other week for a minimum 16 additional weeks until CZP is commercially available.	Placebo n=209 participants at risk Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. From Week 12, 200 mg certolizumab pegol (CZP) given as 1 subcutaneous injection every other week for a minimum 16 additional weeks until CZP is commercially available.	Open Label Certolizumab Pegol (CZP) n=954 participants at risk Subjects entering the open label extension at Week 12 receive 200 mg CZP given every other week for a minimum 16 additional weeks until CZP is commercially available.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	4.4% 37/846 • Number of events 46 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	7.7% 16/209 • Number of events 18 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	7.1% 68/954 • Number of events 83 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.
Nervous system disorders Headache	5.4% 46/846 • Number of events 57 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	5.3% 11/209 • Number of events 13 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	3.7% 35/954 • Number of events 40 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.
Infections and infestations Upper respiratory tract infection	7.3% 62/846 • Number of events 68 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	5.3% 11/209 • Number of events 12 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	8.0% 76/954 • Number of events 83 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.
Infections and infestations Nasopharyngitis	3.2% 27/846 • Number of events 31 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	1.9% 4/209 • Number of events 4 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	5.6% 53/954 • Number of events 58 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.
Infections and infestations Urinary Tract Infection	2.8% 24/846 • Number of events 28 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	4.3% 9/209 • Number of events 10 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.	6.7% 64/954 • Number of events 76 • The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up. Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.

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