Trial Outcomes & Findings for Dosing Flexibility Study in Patients With Rheumatoid Arthritis (NCT NCT00580840)

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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

333 participants

Primary outcome timeframe

Baseline, Week 34

Results posted on

2018-08-02

Participant Flow

The study started in December 2007 with subjects from Canada, France, and United States. The primary completion date occurred in December 2010, with study completion in March 2011.

Participant milestones

Participant milestones
Measure	Overall Overall for the Run-in period includes all 333 subjects that entered the study. Overall for the Double-blind period includes all 209 subjects that completed the Run-in period.	CZP 400 mg and PLO + MTX Certolizumab Pegol (CZP) 400 mg and Placebo (PLO) + Methotrexate (MTX)	CZP 200 mg and PLO + MTX Certolizumab Pegol (CZP) 200 mg and Placebo (PLO) + Methotrexate (MTX)	PLO + MTX Placebo (PTO) + Methotrexate (MTX)
Run-in STARTED	333	0	0	0
Run-in COMPLETED	209	0	0	0
Run-in NOT COMPLETED	124	0	0	0
Double-Blind STARTED	0	70	70	69
Double-Blind COMPLETED	0	63	61	54
Double-Blind NOT COMPLETED	0	7	9	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Overall Overall for the Run-in period includes all 333 subjects that entered the study. Overall for the Double-blind period includes all 209 subjects that completed the Run-in period.	CZP 400 mg and PLO + MTX Certolizumab Pegol (CZP) 400 mg and Placebo (PLO) + Methotrexate (MTX)	CZP 200 mg and PLO + MTX Certolizumab Pegol (CZP) 200 mg and Placebo (PLO) + Methotrexate (MTX)	PLO + MTX Placebo (PTO) + Methotrexate (MTX)
Run-in Adverse Event	17	0	0	0
Run-in Lack of Efficacy	93	0	0	0
Run-in Loss of Efficacy	1	0	0	0
Run-in Lost to Follow-up	4	0	0	0
Run-in Withdrawal by Subject	5	0	0	0
Run-in Other: Per Sponsor Request	2	0	0	0
Run-in Other: Did Not Meet Joint Count Criteria	1	0	0	0
Run-in Other: Exclusionary Lab Value	1	0	0	0
Double-Blind Adverse Event	0	3	4	1
Double-Blind Loss of Efficacy	0	1	2	10
Double-Blind Lost to Follow-up	0	1	0	2
Double-Blind Withdrawal by Subject	0	1	2	2
Double-Blind Other: Discontinued Methotrexate	0	1	0	0
Double-Blind Other: Forbidden Medication	0	0	1	0

Baseline Characteristics

Dosing Flexibility Study in Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Run-in Overall n=333 Participants Overall includes all 333 subjects that entered the Run-in period of the study
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	264 Participants n=5 Participants
Age, Categorical >=65 years	69 Participants n=5 Participants
Age, Continuous	54.2 years STANDARD_DEVIATION 12.75 • n=5 Participants
Sex: Female, Male Female	253 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants
Region of Enrollment France	7 participants n=5 Participants
Region of Enrollment United States	306 participants n=5 Participants
Region of Enrollment Canada	20 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).

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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18	65.2 percentage of subjects	67.1 percentage of subjects	44.9 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis

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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=333 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 16 in All Patients	61.3 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=333 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 16 in All Patients	37.8 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=333 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 16 in All Patients	16.2 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Of the 333 subjects in the Run-in period, 325 are included in this analysis using the Last Observation Carried Forward (LOCF) method.

DAS28-ESR is calculated using the tender joint count (TJC), swollen joint count (SJC) erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. \< 2.6 Remission, \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=325 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 16 in All Patients	-2.3 units on a scale Standard Deviation 1.3	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Of the 333 subjects in the Run-in period, 326 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. \<= 3.3 Remission, \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=326 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 16 in All Patients	-24.1 units on a scale Standard Deviation 13.5	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Of the 333 subjects in the Run-in period, 328 are included in this analysis using the Last Observation Carried Forward (LOCF) method.

CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. The range for the CDAI is 0 - 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=328 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 16 in All Patients	-23.3 units on a scale Standard Deviation 13.2	—	—

SECONDARY outcome

Timeframe: Week 16

Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis

DAS28-ESR is calculated using the tender joint count (TJC), swollen joint count (SJC) erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \< 2.6 (Remission), \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=333 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 16 in All Patients	17.7 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Week 16

Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \<= 3.3 (Remission), \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=333 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 16 in All Patients	15.9 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Week 16

Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). The range for the CDAI is 0 - 76 with a lower CDAI score indicating approvement in activity and a higher score indicating a decline activity.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=333 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 16 in All Patients	17.1 percentage of subjects	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Of the 333 subjects in the Run-in period, 330 are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Ratio is defined as the CRP value at Week 16 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=330 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 16 in All Patients	0.5 Ratio Geometric Coefficient of Variation 122.6	—	—

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Of the 333 subjects in the Run-in period, 330 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). Thus, the mean also has a range from 0-3. Change from baseline is computed as the value at Week 16 minus the 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 400 mg and Placebo + Methotrexate n=330 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 16 in All Patients	-0.5 units on a scale Standard Deviation 0.6	—	—

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).

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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18	52.2 percentage of subjects	50.0 percentage of subjects	30.4 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).

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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18	37.7 percentage of subjects	30.0 percentage of subjects	15.9 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 204 subjects (69 400 mg CZP, 68 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

DAS28-ESR is calculated using the tender joint count (TJC), swollen joint count (SJC) erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward. \< 2.6 Remission, \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=68 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=67 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18	-3.04 units on a scale Standard Error 0.163	-2.83 units on a scale Standard Error 0.164	-1.65 units on a scale Standard Error 0.166

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 70 200 mg CZP, 67 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. \<= 3.3 Remission, \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=68 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=67 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18	-30.46 units on a scale Standard Error 1.554	-28.15 units on a scale Standard Error 1.532	-17.35 units on a scale Standard Error 1.571

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 70 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. Range for CDAI is 0-76 with a lower CDAI score reflects approvement in activity and a higher score reflects a decline.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=67 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18	-29.06 units on a scale Standard Error 1.509	-27.14 units on a scale Standard Error 1.498	-17.03 units on a scale Standard Error 1.536

SECONDARY outcome

Timeframe: Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).

DAS28-ESR is calculated using the tender joint count (TJC), swollen joint count (SJC) erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \< 2.6 (Remission), \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18	29.0 percentage of subjects	18.6 percentage of subjects	5.8 percentage of subjects

SECONDARY outcome

Timeframe: Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).

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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \<= 3.3 (Remission), \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18	29.0 percentage of subjects	17.1 percentage of subjects	13.0 percentage of subjects

SECONDARY outcome

Timeframe: Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).

CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). The range for the CDAI is 0 - 76 with a lower CDAI score indicating approvement in activity and a higher score indicating a decline activity.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18	27.5 percentage of subjects	21.4 percentage of subjects	15.9 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Ratio is defined as the CRP value at Week 34 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method with an ANCOVA model on observed log transformed data with factors treatment and log transformed Baseline CRP level. The number presented is the geometric least squares mean with it's 95% confidence interval.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18	0.44 Ratio Interval 0.36 to 0.53	0.48 Ratio Interval 0.4 to 0.58	0.82 Ratio Interval 0.68 to 0.99

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 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). Thus, the mean also has a range from 0-3. Change from baseline is computed as the value at Week 34 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18	-0.64 units on a scale Standard Error 0.060	-0.72 units on a scale Standard Error 0.060	-0.38 units on a scale Standard Error 0.061

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 70 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in Fatigue Assessment scale (0 to 10, 0 is "No Fatigue" and 10 is "Fatigue as bad as you can imagine") is computed as the value at Week 34 minus the Baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=68 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=67 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18	-2.39 units on a scale Standard Error 0.261	-3.03 units on a scale Standard Error 0.258	-1.33 units on a scale Standard Error 0.264

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	8.39 units on a scale Standard Error 1.080	9.07 units on a scale Standard Error 1.076	4.09 units on a scale Standard Error 1.086

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=69 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	9.80 units on a scale Standard Error 1.095	11.06 units on a scale Standard Error 1.097	7.14 units on a scale Standard Error 1.099

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=69 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	12.95 units on a scale Standard Error 1.042	11.28 units on a scale Standard Error 1.044	6.12 units on a scale Standard Error 1.047

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=68 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=69 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	5.46 units on a scale Standard Error 0.959	5.51 units on a scale Standard Error 0.956	3.16 units on a scale Standard Error 0.961

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=68 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=69 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	9.88 units on a scale Standard Error 1.127	11.53 units on a scale Standard Error 1.123	5.47 units on a scale Standard Error 1.129

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	8.87 units on a scale Standard Error 1.179	10.03 units on a scale Standard Error 1.170	6.42 units on a scale Standard Error 1.187

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 204 subjects (67 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=67 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=69 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	6.86 units on a scale Standard Error 1.322	8.86 units on a scale Standard Error 1.313	5.86 units on a scale Standard Error 1.306

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=68 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=69 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18	5.38 units on a scale Standard Error 1.050	7.44 units on a scale Standard Error 1.042	4.13 units on a scale Standard Error 1.049

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 202 subjects (66 400 mg CZP, 68 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

PCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from 1 to 81, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=66 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=68 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18	10.54 units on a scale Standard Error 0.939	9.65 units on a scale Standard Error 0.928	5.09 units on a scale Standard Error 0.926

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 202 subjects (66 400 mg CZP, 68 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

MCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from -9 to 82, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=66 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=68 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18	5.51 units on a scale Standard Error 1.162	8.59 units on a scale Standard Error 1.147	4.90 units on a scale Standard Error 1.143

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in Patient's Assessment of Arthritis Pain-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 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18	-36.41 units on a scale Standard Error 2.894	-34.33 units on a scale Standard Error 2.869	-17.47 units on a scale Standard Error 2.911

SECONDARY outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in Patient's Global Assessment of Disease Activity-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18	-35.58 units on a scale Standard Error 2.966	-33.07 units on a scale Standard Error 2.946	-16.37 units on a scale Standard Error 2.987

SECONDARY outcome

Timeframe: Week 18 up to Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis.

ACR20 loss are subjects with \<20% improvement from Baseline for tender joint count, swollen joint count, and at least 3/5 core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein, 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale at 2 consecutive visits. Subjects losing response for 2 consecutive visits are considered as having the event on the day of the visit where response was first lost.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18.	NA days Interval 100.0 to Because the analysis was run on the Full Analysis Set (FAS) the survival curves drop dramatically initially causing values to be non-computable.	NA days Because the analysis was run on the Full Analysis Set (FAS) the survival curves drop dramatically initially causing values to be non-computable.	98.0 days Interval 17.0 to Because the analysis was run on the Full Analysis Set (FAS) the survival curves drop dramatically initially causing values to be non-computable.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Of the 333 subjects in the Run-in period, 328 are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Ratio is defined as the ESR value at Week 16 divided by the ESR value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=328 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 16 in All Patients	0.6 Ratio Geometric Coefficient of Variation 76.7	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (69 400 mg CZP, 68 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Ratio is defined as the ESR value at Week 34 divided by the ESR value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method with an ANCOVA model on observed log transformed data with factors treatment and log transformed Baseline CRP level. The number presented is the geometric least squares mean with it's 95% confidence interval.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=68 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 34 in Patients Randomized at Week 18	0.56 Ratio Interval 0.48 to 0.65	0.62 Ratio Interval 0.53 to 0.72	0.84 Ratio Interval 0.71 to 0.98

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 70 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in Physician's Global Assessment of Disease Activity-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=67 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in PhGADA (Physician's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18	-44.62 units on a scale Standard Error 2.428	-40.24 units on a scale Standard Error 2.427	-25.97 units on a scale Standard Error 2.476

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in Tender Joint Count is computed as the value at Week 34 minus the Baseline value (28 joints were assessed at each visit). A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in TJC (Tender Joint Count) at Week 34 in Patients Randomized at Week 18	-11.81 Joints Standard Error 0.702	-11.33 Joints Standard Error 0.692	-7.16 Joints Standard Error 0.707

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 34

Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.

Change from Baseline in Swollen Joint Count is computed as the value at Week 34 minus the Baseline value (28 joints were assessed at each visit). A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 Participants 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 Participants 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=68 Participants Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Change From Baseline in SJC (Swollen Joint Count) at Week 34 in Patients Randomized at Week 18	-9.29 Joints Standard Error 0.542	-8.37 Joints Standard Error 0.540	-5.41 Joints Standard Error 0.547

Adverse Events

Run-in Overall

Serious events: 18 serious events

Other events: 80 other events

Deaths: 0 deaths

Certolizumab Pegol 400 mg and Placebo + Methotrexate

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Certolizumab Pegol 200 mg and Placebo + Methotrexate

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo + Methotrexate

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Run-in Overall n=333 participants at risk Overall includes all 333 subjects that entered the Run-in period of the study	Certolizumab Pegol 400 mg and Placebo + Methotrexate n=69 participants at risk 400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks) plus a subject specific dose of methotrexate	Certolizumab Pegol 200 mg and Placebo + Methotrexate n=70 participants at risk 200 mg certolizumab pegol and placebo administered every 2 weeks (one injection of each) plus a subject specific dose of methotrexate	Placebo + Methotrexate n=69 participants at risk Placebo administered as two injections every 2 weeks plus a subject specific dose of methotrexate
Infections and infestations Nasopharyngitis	2.1% 7/333 • Number of events 7 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	1.4% 1/69 • Number of events 1 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	1.4% 1/70 • Number of events 1 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	5.8% 4/69 • Number of events 4 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.
Infections and infestations Upper respiratory tract infection	12.6% 42/333 • Number of events 46 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	11.6% 8/69 • Number of events 8 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	7.1% 5/70 • Number of events 6 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	14.5% 10/69 • Number of events 11 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.
Infections and infestations Urinary tract infection	8.1% 27/333 • Number of events 31 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	8.7% 6/69 • Number of events 6 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	7.1% 5/70 • Number of events 5 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	10.1% 7/69 • Number of events 8 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.
Musculoskeletal and connective tissue disorders Arthralgia	3.0% 10/333 • Number of events 12 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	7.2% 5/69 • Number of events 5 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	1.4% 1/70 • Number of events 1 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	2.9% 2/69 • Number of events 2 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	2.7% 9/333 • Number of events 10 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	2.9% 2/69 • Number of events 2 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	1.4% 1/70 • Number of events 2 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.	8.7% 6/69 • Number of events 6 • The first column represents Adverse Event (AE) reporting for the 16-Week run-in period. The last three columns represents AE reporting for the 18-Week double-blind period. Of the 209 randomized participants, 208 are in the Full Analysis Set (FAS), as 1 subject was randomized but did not receive treatment during the Double-Blind (DB) period.

Additional Information

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Phone: +1 887 822 9493

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