Trial Outcomes & Findings for A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid Arthritis (NCT NCT01519791)

NCT ID: NCT01519791

Last Updated: 2018-07-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

880 participants

Primary outcome timeframe

Week 52

Results posted on

2018-07-31

Participant Flow

This study started to enroll subjects in January 2012.

A total of 880 subjects were randomized. Three subjects were randomized in error, were not dosed, and withdrawn shortly afterwards as screen failures. Two of them were included in the Randomized Set 1 (RS1) only and one of these three subjects was conservatively excluded from any output. Therefore, 879 subjects are in RS1.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	219	660
Overall Study Completed Week 52	143	500
Overall Study COMPLETED	67	292
Overall Study NOT COMPLETED	152	368

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study SAE,non-fatal + AE,non-serious non-fatal	2	1
Overall Study Protocol Violation	6	19
Overall Study Other Reason	87	222
Overall Study subjects randomized in error	2	0
Overall Study Lack of Efficacy	16	20
Overall Study SAE, non-fatal	6	22
Overall Study AE, serious fatal	0	1
Overall Study SAE, fatal + SAE, non-fatal	0	1
Overall Study AE, non-serious non-fatal	12	31
Overall Study Withdrawal by Subject	15	37
Overall Study Lost to Follow-up	6	14

Baseline Characteristics

A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Methotrexate n=219 Participants 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.	Certolizumab Pegol + Methotrexate n=660 Participants 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.	Total Title n=879 Participants
Age, Categorical <=18 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	182 Participants n=5 Participants	560 Participants n=7 Participants	742 Participants n=5 Participants
Age, Categorical >=65 years	36 Participants n=5 Participants	98 Participants n=7 Participants	134 Participants n=5 Participants
Age, Continuous	51.3 years STANDARD_DEVIATION 13.2 • n=5 Participants	50.5 years STANDARD_DEVIATION 13.6 • n=7 Participants	50.7 years STANDARD_DEVIATION 13.5 • n=5 Participants
Sex: Female, Male Female	175 Participants n=5 Participants	499 Participants n=7 Participants	674 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	161 Participants n=7 Participants	205 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 52

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects in Sustained Remission at Week 52	15.0 percentage of subjects	28.9 percentage of subjects

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52	28.6 percentage of subjects	43.8 percentage of subjects

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=163 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=528 Participants 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.
Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52	1.8 units on a scale Standard Deviation 4.3	0.2 units on a scale Standard Deviation 3.2

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=163 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=528 Participants 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.
Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52	49.7 percentage of subjects	70.3 percentage of subjects

SECONDARY outcome

Timeframe: From Baseline (Week 0) 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=163 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=528 Participants 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.
Change From Baseline in the Joint Erosion Score to Week 52	1.1 units on a scale Standard Deviation 3.0	0.1 units on a scale Standard Deviation 2.1

SECONDARY outcome

Timeframe: From Baseline (Week 0) 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=163 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=528 Participants 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.
Change From Baseline in the Joint Narrowing Score to Week 52	0.7 units on a scale Standard Deviation 2.3	0.1 units on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: From Baseline (Week 0) to 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).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52	61.5 percentage of subjects	69.0 percentage of subjects

SECONDARY outcome

Timeframe: From Baseline (Week 0) to 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).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52	52.6 percentage of subjects	61.8 percentage of subjects

SECONDARY outcome

Timeframe: From Baseline (Week 0) to 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).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52	39.9 percentage of subjects	51.3 percentage of subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52	20.7 percentage of subjects	32.4 percentage of subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52	26.3 percentage of subjects	38.9 percentage of subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52	24.9 percentage of subjects	38.9 percentage of subjects

SECONDARY outcome

Timeframe: Week 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52	26.8 percentage of subjects	42.6 percentage of subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
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	24.9 percentage of subjects	35.3 percentage of subjects

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52	82.2 percentage of subjects	89.9 percentage of subjects

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=210 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=646 Participants 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.
Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52	-3.014 units on a scale Standard Error 0.109	-3.615 units on a scale Standard Error 0.069

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=210 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=644 Participants 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.
Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52	-29.09 units on a scale Standard Error 0.84	-33.11 units on a scale Standard Error 0.52

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=210 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=644 Participants 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.
Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52	-30.24 units on a scale Standard Error 0.88	-34.55 units on a scale Standard Error 0.55

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52	35.7 percentage of subjects	48.1 percentage of subjects

SECONDARY outcome

Timeframe: From Baseline (Week 0) 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=210 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=645 Participants 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.
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52	-0.819 units on a scale Standard Error 0.044	-0.997 units on a scale Standard Error 0.028

SECONDARY outcome

Timeframe: From Baseline (Week 0) 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=205 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=636 Participants 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.
Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52	-15.6 units on a scale Standard Error 1.0	-17.8 units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=106 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=351 Participants 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.
Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	0.9 days Standard Deviation 2.5	0.6 days Standard Deviation 2.6

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=106 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=351 Participants 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.
Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	1.8 days Standard Deviation 4.7	1.0 days Standard Deviation 3.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=106 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=351 Participants 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.
Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	1.9 units on a scale Standard Deviation 2.3	1.4 units on a scale Standard Deviation 2.0

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=206 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=640 Participants 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.
Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	3.0 days Standard Deviation 6.7	1.9 days Standard Deviation 5.1

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=206 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=640 Participants 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.
Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	3.0 days Standard Deviation 6.6	2.1 days Standard Deviation 5.3

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=206 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=640 Participants 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.
Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	0.7 days Standard Deviation 3.3	0.6 days Standard Deviation 3.2

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=206 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=640 Participants 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.
Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	0.9 days Standard Deviation 3.1	0.9 days Standard Deviation 3.6

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=206 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=640 Participants 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.
Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52	2.5 units on a scale Standard Deviation 2.8	1.9 units on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: Week 52

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

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate (Full Analysis Set) n=213 Participants 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.	Certolizumab Pegol + Methotrexate (Full Analysis Set) n=655 Participants 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.
Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52	39.4 percentage of subjects	54.7 percentage of subjects

Adverse Events

Placebo + Methotrexate

Serious events: 20 serious events

Other events: 63 other events

Deaths: 0 deaths

Certolizumab Pegol + Methotrexate

Serious events: 70 serious events

Other events: 248 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo + Methotrexate n=217 participants at risk 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.	Certolizumab Pegol + Methotrexate n=659 participants at risk 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.
Gastrointestinal disorders Nausea	10.1% 22/217 • Number of events 22 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.	12.6% 83/659 • Number of events 92 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.
Infections and infestations Upper respiratory tract infection	5.1% 11/217 • Number of events 12 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.	10.9% 72/659 • Number of events 86 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.
Infections and infestations Urinary tract infection	7.4% 16/217 • Number of events 18 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.	7.3% 48/659 • Number of events 63 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.
Infections and infestations Nasopharyngitis	6.0% 13/217 • Number of events 17 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.	7.0% 46/659 • Number of events 60 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.
Investigations Alanine aminotransferase increased	4.1% 9/217 • Number of events 13 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.	6.4% 42/659 • Number of events 46 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.
Nervous system disorders Headache	3.7% 8/217 • Number of events 11 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.	6.8% 45/659 • Number of events 65 • Adverse Events were collected from Screening over Baseline (Week 0) and Treatment Period 1 (Week 2 to Week 52) to the Safety Follow-Up Visit (Week 60). Adverse Events presented below refer to the Safety Set 1 (SS1), which consisted of all subjects in the Randomized Set who had received at least 1 dose of study medication (CZP/PBO) in Period 1.

Additional Information

UCB (Study Director)

UCB Clinical Trial Call Center

Phone: +1 887 822 9493

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60