A Multi-center, Randomized, Double-blind, Placebo-control... | NCT01519791

ID	Type	Description	Link
2011-001729-25	EudraCT Number

Label	Type	Description	Intervention Names
Certolizumab Pegol + Methotrexate	Experimental		Biological: Certolizumab Pegol Biological: Methotrexate
Placebo + Methotrexate	Placebo Comparator		Other: Placebo Biological: Methotrexate

Name	Type	Description	Arm Group Labels	Other Names
Certolizumab Pegol	Biological	Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg at Baseline, Week 2 and Week 4, followed by a maintenance dose of 200 mg every 2 Weeks until Week 50.

Measure	Description	Time Frame
Percentage of Subjects in Sustained Remission at Week 52	Sustained remission is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at both Weeks 40 and 52. 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 (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.	Week 52

Measure	Description	Time Frame
Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52	Sustained LDA is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) ≤ 3.2 at both Weeks 40 and 52.	Week 52
Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52

Name	Affiliation	Role
UCB Clinical Trial Call Center	+1 877 822 9493 (UCB)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
209		Birmingham	Alabama		United States
170

PubMed Identifier	Type	Citation	Retractions
27165179	Result	Emery P, Bingham CO 3rd, Burmester GR, Bykerk VP, Furst DE, Mariette X, van der Heijde D, van Vollenhoven R, Arendt C, Mountian I, Purcaru O, Tatla D, VanLunen B, Weinblatt ME. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naive patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study. Ann Rheum Dis. 2017 Jan;76(1):96-104. doi: 10.1136/annrheumdis-2015-209057. Epub 2016 May 10.
28666080

Label	URL
FDA Safety Alerts and Recalls	View source

ID	Title	Description
FG000	Placebo + Methotrexate	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Subjects in Sustained Remission at Week 52

Sustained remission is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at both Weeks 40 and 52.

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 (PtGADA-VAS in mm) using the following formula:

0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.

Full Analysis Set Period 1 (FAS1) with Non-Responder Imputation (NRI). FAS1 consisted of all subjects with valid Baseline and valid post-Baseline efficacy measurement within Period 1 for DAS28(ESR). For NRI, a subject having missing data for the time point assessed was conservatively counted as a nonremitter or nonresponder.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Units	Counts
Participants	OG000213 OG001655

Title

Denominators

Categories

Title	Measurements
	OG00015.0 OG00128.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	In order to control the overall study-wise Type I error rate at 5 %, hypothesis testing was performed in the following hierarchical order (each at a 2-sided 95 % alpha level): Primary: sustained DAS28(ESR) remission at Week 52 Key secondary: sustained DAS28(ESR) LDA at Week 52 ACR50 response at Week 52 in relation to Baseline Change from Baseline in HAQ-DI at Week 52 Change from Baseline in mTSS at Week 52	Regression, Logistic		<0.001		Odds Ratio (OR)	2.283			2-Sided	95	1.503	3.468			The Odds ratio measuring the treatment effect was estimated from a logistic regression model including terms for treatment, region and stratification factor. Nonresponder imputation (NRI) was used.

Secondary

Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52

Sustained LDA is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) ≤ 3.2 at both Weeks 40 and 52.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52

Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.

The Radiographic Set Period 1 (RAD1) consisted of those subjects in the FAS1 who had provided valid radiographs (ie, radiographs resulting in a nonmissing mTSS score) at Baseline and at Week 52 or the Withdrawal Visit.

Posted

Mean

Standard Deviation

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Radiographic Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Radiographic Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52

Radiographic non-progression is defined as change in mTSS ≤ 0.5.

Posted

Number

percentage of subjects

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Radiographic Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Radiographic Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Change From Baseline in the Joint Erosion Score to Week 52

Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.

The maximum possible erosion score for all 32-hand joints was 160. The maximum possible erosion score for all 12 feet joints was 120. Thus, the maximum possible total erosion score for hands and feet was 280.

Posted

Mean

Standard Deviation

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Radiographic Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Radiographic Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Change From Baseline in the Joint Narrowing Score to Week 52

Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The maximum possible score for JSN in all 30 hand joints was 120. The maximum possible score for JSN in all 12 feet joints was 48. Thus, the maximum possible total JSN score for Hands and feet was 168.

Posted

Mean

Standard Deviation

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Radiographic Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Radiographic Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52

The assessments are based on a 20 % or greater improvement from Baseline in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

Posted

Number

percentage of subjects

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)

Secondary

Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52

The assessments are based on a 50 % or greater improvement from Baseline in the number of tender joints, a 50 %, or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

Posted

Number

percentage of subjects

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)

Secondary

Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52

The assessments are based on a 70 % or greater improvement from Baseline in the number of tender joints, a 70 %, or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

Posted

Number

percentage of subjects

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)

Secondary

Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52

The ACR/EULAR 2011 remission criteria is defined as:

Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1, C-reactive protein (CRP) ≤ 1 mg/dl and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52

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 (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52

SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52

0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice at Week 52

The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:

Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52

Good response is defined as:

DAS28[ESR] ≤ 3.2 and decrease from Baseline by > 1.2;

moderate response is defined as achievement of one of the following:

DAS28[ESR] ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2
DAS28[ESR] > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6
DAS28[ESR] > 5.1 and decrease from Baseline >1.2.

Full Analysis Set Period 1 (FAS1). The FAS1 consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement within Period 1 for the primary efficacy assessment of DAS28(ESR).

Posted

Number

percentage of subjects

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52

0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.

Full Analysis Set Period 1 (FAS1) with Last Observation Carried Forward (LOCF). The FAS1 consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement within Period 1 for the primary efficacy assessment of DAS28(ESR). Missing DAS28(ESR) values were imputed using LOCF.

Posted

Least Squares Mean

Standard Error

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)

Secondary

Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52

The CDAI score ranges from 0 to 76, with a negative value in CDAI change from Baseline indicating an improvement from Baseline.

Posted

Least Squares Mean

Standard Error

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52

The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline.

Posted

Least Squares Mean

Standard Error

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)

Secondary

Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52

Normative physical function is defined as HAQ-DI score ≤ 0.5. The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.

The total score ranges from 0 to 3 with lower scores meaning lower disability.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52

The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.

The total score ranges from 0 (no difficulty) to 3 (unable to do) with lower scores meaning lower disability.

A negative value in HAQ-DI change from Baseline indicates an improvement from Baseline.

Posted

Least Squares Mean

Standard Error

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52

BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue).

A negative value in BRAF-MDQ change from Baseline indicates an improvement from Baseline.

Posted

Least Squares Mean

Standard Error

units on a scale

From Baseline (Week 0) to Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

Number of work days missed in the last month for employed subjects.

Posted

Mean

Standard Deviation

days

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

Number of work days with reduced productivity in the last month for employed subjects.

Posted

Mean

Standard Deviation

days

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference) for employed subjects.

Posted

Mean

Standard Deviation

units on a scale

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

Number of days with no household work in the last month.

Posted

Mean

Standard Deviation

days

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

Number of days with reduced household work productivity in the last month.

Posted

Mean

Standard Deviation

days

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

Number of days with hired outside help in the last month.

Posted

Mean

Standard Deviation

days

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

Number of days missed of family/social/leisure activities in the last month.

Posted

Mean

Standard Deviation

days

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52

The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).

Posted

Mean

Standard Deviation

units on a scale

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Secondary

Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52

LDA is defined as achieving a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2.

Posted

Number

percentage of subjects

Week 52

ID	Title	Description
OG000	Placebo + Methotrexate (Full Analysis Set)	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
OG001	Certolizumab Pegol + Methotrexate (Full Analysis Set)	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0015 events3 affected659 at risk
Bone marrow toxicity	Blood and lymphatic system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0012 events2 affected659 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Atrial fibrillation	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0011 events1 affected659 at risk
Cardiac arrest	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Cardiac failure	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Cardiac tamponade	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Myocardial infarction	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Pericarditis	Cardiac disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Colitis	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Erosive duodenitis	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Gastrointestinal ulcer haemorrhage	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Mesenteric panniculitis	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Nausea	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0012 events2 affected659 at risk
Anaphylactic shock	Immune system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Food allergy	Immune system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Abscess limb	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Appendiceal abscess	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Arthritis infective	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Breast abscess	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Bronchitis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Bronchopneumonia	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Cellulitis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0012 events2 affected659 at risk
Erysipelas	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Gastroenteritis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Groin abscess	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Herpes zoster	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Impetigo	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Influenza	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Kidney infection	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Labyrinthitis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Latent tuberculosis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0002 events2 affected217 at risk EG0011 events1 affected659 at risk
Localised infection	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Pneumonia	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0003 events3 affected217 at risk EG0014 events4 affected659 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Sepsis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Staphylococcal infection	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Tuberculosis gastrointestinal	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Urosepsis	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Wound infection	Infections and infestations	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Fall	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0012 events1 affected659 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0012 events2 affected659 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Lupus-like syndrome	Musculoskeletal and connective tissue disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0014 events4 affected659 at risk
Rheumatoid nodule	Musculoskeletal and connective tissue disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0012 events1 affected659 at risk
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0011 events1 affected659 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Chondrosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0011 events1 affected659 at risk
Cervicobrachial syndrome	Nervous system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Ischaemic stroke	Nervous system disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0011 events1 affected659 at risk
Loss of consciousness	Nervous system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Migraine	Nervous system disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Bladder outlet obstruction	Renal and urinary disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Renal failure	Renal and urinary disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0011 events1 affected659 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0014 events2 affected659 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Epiglottic cyst	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0012 events2 affected659 at risk
Laryngeal polyp	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0002 events2 affected217 at risk EG0010 events0 affected659 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0002 events2 affected217 at risk EG0011 events1 affected659 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0013 events1 affected659 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA17.0	Non-systematic Assessment	EG0002 events1 affected217 at risk EG0010 events0 affected659 at risk
Coronary arterial stent insertion	Surgical and medical procedures	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Hip arthroplasty	Surgical and medical procedures	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Leg amputation	Surgical and medical procedures	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0012 events1 affected659 at risk
Aortic aneurysm	Vascular disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Aortic stenosis	Vascular disorders	MedDRA17.0	Non-systematic Assessment	EG0000 events0 affected217 at risk EG0011 events1 affected659 at risk
Arteriosclerosis	Vascular disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk
Deep vein thrombosis	Vascular disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0011 events1 affected659 at risk
Orthostatic hypotension	Vascular disorders	MedDRA17.0	Non-systematic Assessment	EG0001 events1 affected217 at risk EG0010 events0 affected659 at risk

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D011092	Polyethylene Glycols
D011108	Polymers
D046911	Macromolecular Substances
D007140	Immunoglobulin Fab Fragments
D007128	Immunoglobulin Fragments
D010446	Peptide Fragments
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D012712	Serum Globulins
D005916	Globulins
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Placebo + Methotrexate	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
BG001	Certolizumab Pegol + Methotrexate	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.
BG002	Total Title

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo + Methotrexate	Placebo + Methotrexate (MTX) 2 syringes Placebo at Baseline, Week 2 and Week 4 + MTX, followed by 1 syringe Placebo every 2 Weeks + MTX. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.			20	217	63	217
EG001	Certolizumab Pegol + Methotrexate	Certolizumab Pegol + Methotrexate (MTX) Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg + MTX at Baseline, Week 2 and Week 4, followed by a maintenance dose of CZP 200 mg + MTX every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week. The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8.			70	659	248	659