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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 (C-early)

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ClinicalTrials.gov Identifier: NCT01519791
Recruitment Status : Completed
First Posted : January 27, 2012
Results First Posted : September 22, 2015
Last Update Posted : July 31, 2018
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Biological: Certolizumab Pegol
Other: Placebo
Biological: Methotrexate
Enrollment 880
Recruitment Details This study started to enroll subjects in January 2012.
Pre-assignment Details 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 Three subjects were randomized in error, were not dosed, and withdrawn shortly afterwards as screen failures.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.
Arm/Group Title Placebo + Methotrexate Certolizumab Pegol + Methotrexate
Hide Arm/Group Description

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 (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.

Period Title: Overall Study
Started 219 660
Completed Week 52 143 500
Completed 67 292
Not Completed 152 368
Reason Not Completed
SAE,non-fatal + AE,non-serious non-fatal             2             1
Protocol Violation             6             19
Other Reason             87             222
subjects randomized in error             2             0
Lack of Efficacy             16             20
SAE, non-fatal             6             22
AE, serious fatal             0             1
SAE, fatal + SAE, non-fatal             0             1
AE, non-serious non-fatal             12             31
Withdrawal by Subject             15             37
Lost to Follow-up             6             14
Arm/Group Title Placebo + Methotrexate Certolizumab Pegol + Methotrexate Total Title
Hide Arm/Group Description

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 (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.

[Not Specified]
Overall Number of Baseline Participants 219 660 879
Hide Baseline Analysis Population Description
Baseline Charactersitics refer to the Randomized Set (RS).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 660 participants 879 participants
<=18 years
1
   0.5%
2
   0.3%
3
   0.3%
Between 18 and 65 years
182
  83.1%
560
  84.8%
742
  84.4%
>=65 years
36
  16.4%
98
  14.8%
134
  15.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 219 participants 660 participants 879 participants
51.3  (13.2) 50.5  (13.6) 50.7  (13.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 660 participants 879 participants
Female
175
  79.9%
499
  75.6%
674
  76.7%
Male
44
  20.1%
161
  24.4%
205
  23.3%
1.Primary Outcome
Title Percentage of Subjects in Sustained Remission at Week 52
Hide Description

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.

Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
15.0 28.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate (Full Analysis Set), Certolizumab Pegol + Methotrexate (Full Analysis Set)
Comments

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):

  1. Primary: sustained DAS28(ESR) remission at Week 52
  2. Key secondary: sustained DAS28(ESR) LDA at Week 52
  3. ACR50 response at Week 52 in relation to Baseline
  4. Change from Baseline in HAQ-DI at Week 52
  5. Change from Baseline in mTSS at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.283
Confidence Interval (2-Sided) 95%
1.503 to 3.468
Estimation Comments 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.
2.Secondary Outcome
Title Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52
Hide Description Sustained LDA is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) ≤ 3.2 at both Weeks 40 and 52.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
28.6 43.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate (Full Analysis Set), Certolizumab Pegol + Methotrexate (Full Analysis Set)
Comments

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):

  1. Primary: sustained DAS28(ESR) remission at Week 52
  2. Key secondary: sustained DAS28(ESR) LDA at Week 52
  3. ACR50 response at Week 52 in relation to Baseline
  4. Change from Baseline in HAQ-DI at Week 52
  5. Change from Baseline in mTSS at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.957
Confidence Interval (2-Sided) 95%
1.384 to 2.767
Estimation Comments 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.
3.Secondary Outcome
Title Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52
Hide Description 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.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Radiographic Set) Certolizumab Pegol + Methotrexate (Radiographic Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 163 528
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.8  (4.3) 0.2  (3.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate (Radiographic Set), Certolizumab Pegol + Methotrexate (Radiographic Set)
Comments

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):

  1. Primary: sustained DAS28(ESR) remission at Week 52
  2. Key secondary: sustained DAS28(ESR) LDA at Week 52
  3. ACR50 response at Week 52 in relation to Baseline
  4. Change from Baseline in HAQ-DI at Week 52
  5. Change from Baseline in mTSS at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA on ranks
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann point estimate of shift
Estimated Value -0.978
Confidence Interval (2-Sided) 95%
-1.005 to -0.500
Estimation Comments

ANCOVA model on the ranks with the terms for treatment, region, and time since RA diagnosis at Baseline (≤4 months or >4 months) as factors and rank Baseline value as a covariate.

Confidence Interval is an asymptotic Moses CI.

4.Secondary Outcome
Title Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52
Hide Description Radiographic non-progression is defined as change in mTSS ≤ 0.5.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Radiographic Set) Certolizumab Pegol + Methotrexate (Radiographic Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 163 528
Measure Type: Number
Unit of Measure: percentage of subjects
49.7 70.3
5.Secondary Outcome
Title Change From Baseline in the Joint Erosion Score to Week 52
Hide Description

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.

Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Radiographic Set) Certolizumab Pegol + Methotrexate (Radiographic Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 163 528
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.1  (3.0) 0.1  (2.1)
6.Secondary Outcome
Title Change From Baseline in the Joint Narrowing Score to Week 52
Hide Description 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.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Radiographic Set) Certolizumab Pegol + Methotrexate (Radiographic Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 163 528
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.7  (2.3) 0.1  (1.7)
7.Secondary Outcome
Title Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52
Hide Description 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).
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
61.5 69.0
8.Secondary Outcome
Title Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52
Hide Description 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).
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
52.6 61.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate (Full Analysis Set), Certolizumab Pegol + Methotrexate (Full Analysis Set)
Comments

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):

  1. Primary: sustained DAS28(ESR) remission at Week 52
  2. Key secondary: sustained DAS28(ESR) LDA at Week 52
  3. ACR50 response at Week 52 in relation to Baseline
  4. Change from Baseline in HAQ-DI at Week 52
  5. Change from Baseline in mTSS at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.023
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.446
Confidence Interval (2-Sided) 95%
1.052 to 1.989
Estimation Comments The Odds ratio was estimated from a logistic regression model including terms for treatment, region and stratification factor. Nonresponder imputation (NRI) was used.
9.Secondary Outcome
Title Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52
Hide Description 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).
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
39.9 51.3
10.Secondary Outcome
Title Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52
Hide Description

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.

Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
20.7 32.4
11.Secondary Outcome
Title Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52
Hide Description 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.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
26.3 38.9
12.Secondary Outcome
Title Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52
Hide Description 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.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
24.9 38.9
13.Secondary Outcome
Title Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52
Hide Description

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.

Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
26.8 42.6
14.Secondary Outcome
Title 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
Hide Description

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.

Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
24.9 35.3
15.Secondary Outcome
Title Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52
Hide Description

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.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
82.2 89.9
16.Secondary Outcome
Title Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52
Hide Description

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. A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.

Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 210 646
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.014  (0.109) -3.615  (0.069)
17.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52
Hide Description

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.

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

Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 CDAI values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 210 644
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-29.09  (0.84) -33.11  (0.52)
18.Secondary Outcome
Title Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52
Hide Description

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.

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

Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 SDAI values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 210 644
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-30.24  (0.88) -34.55  (0.55)
19.Secondary Outcome
Title Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52
Hide Description

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.

Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
35.7 48.1
20.Secondary Outcome
Title Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52
Hide Description

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.

Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 HAQ-DI values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 210 645
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.819  (0.044) -0.997  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Methotrexate (Full Analysis Set), Certolizumab Pegol + Methotrexate (Full Analysis Set)
Comments

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):

  1. Primary: sustained DAS28(ESR) remission at Week 52
  2. Key secondary: sustained DAS28(ESR) LDA at Week 52
  3. ACR50 response at Week 52 in relation to Baseline
  4. Change from Baseline in HAQ-DI at Week 52
  5. Change from Baseline in mTSS at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares (LS) Means
Estimated Value -0.177
Confidence Interval (2-Sided) 95%
-0.273 to -0.082
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.049
Estimation Comments The CfB in HAQ-DI at Week 52 was analyzed using an ANCOVA model with terms for treatment, region, and time since Rheumatoid Arthritis (RA) diagnosis at Baseline (≤4 months or >4 months) as factors and Baseline value as a covariate.
21.Secondary Outcome
Title Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52
Hide Description

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.

Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 BRAF-MDQ values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 205 636
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-15.6  (1.0) -17.8  (0.6)
22.Secondary Outcome
Title Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description Number of work days missed in the last month for employed subjects.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 106 351
Mean (Standard Deviation)
Unit of Measure: days
0.9  (2.5) 0.6  (2.6)
23.Secondary Outcome
Title Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description Number of work days with reduced productivity in the last month for employed subjects.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 106 351
Mean (Standard Deviation)
Unit of Measure: days
1.8  (4.7) 1.0  (3.4)
24.Secondary Outcome
Title Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description 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.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 106 351
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.9  (2.3) 1.4  (2.0)
25.Secondary Outcome
Title Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description Number of days with no household work in the last month.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 206 640
Mean (Standard Deviation)
Unit of Measure: days
3.0  (6.7) 1.9  (5.1)
26.Secondary Outcome
Title Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description Number of days with reduced household work productivity in the last month.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 206 640
Mean (Standard Deviation)
Unit of Measure: days
3.0  (6.6) 2.1  (5.3)
27.Secondary Outcome
Title Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description Number of days with hired outside help in the last month.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 206 640
Mean (Standard Deviation)
Unit of Measure: days
0.7  (3.3) 0.6  (3.2)
28.Secondary Outcome
Title Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description Number of days missed of family/social/leisure activities in the last month.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 206 640
Mean (Standard Deviation)
Unit of Measure: days
0.9  (3.1) 0.9  (3.6)
29.Secondary Outcome
Title Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Hide Description 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).
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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 WPS-RA values were imputed using LOCF.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 206 640
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.5  (2.8) 1.9  (2.5)
30.Secondary Outcome
Title Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52
Hide Description LDA is defined as achieving a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Methotrexate (Full Analysis Set) Certolizumab Pegol + Methotrexate (Full Analysis Set)
Hide Arm/Group Description:

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 (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 Number of Participants Analyzed 213 655
Measure Type: Number
Unit of Measure: percentage of subjects
39.4 54.7
Time Frame 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 Event Reporting Description 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.
 
Arm/Group Title Placebo + Methotrexate Certolizumab Pegol + Methotrexate
Hide Arm/Group Description

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 (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.

All-Cause Mortality
Placebo + Methotrexate Certolizumab Pegol + Methotrexate
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + Methotrexate Certolizumab Pegol + Methotrexate
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/217 (9.22%)      70/659 (10.62%)    
Blood and lymphatic system disorders     
Anaemia * 1  0/217 (0.00%)  0 3/659 (0.46%)  5
Bone marrow toxicity * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Iron deficiency anaemia * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Pancytopenia * 1  0/217 (0.00%)  0 2/659 (0.30%)  2
Cardiac disorders     
Acute myocardial infarction * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Atrial fibrillation * 1  1/217 (0.46%)  1 1/659 (0.15%)  1
Cardiac arrest * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Cardiac failure * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Cardiac tamponade * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Myocardial infarction * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Myocardial ischaemia * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Pericarditis * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Gastrointestinal disorders     
Colitis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Duodenal ulcer * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Erosive duodenitis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Gastritis erosive * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Gastrointestinal ulcer haemorrhage * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Gastrooesophageal reflux disease * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Mesenteric panniculitis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Mouth ulceration * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Nausea * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Pancreatitis acute * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Rectal haemorrhage * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Upper gastrointestinal haemorrhage * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Hepatobiliary disorders     
Bile duct stone * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Cholecystitis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Cholelithiasis * 1  0/217 (0.00%)  0 2/659 (0.30%)  2
Immune system disorders     
Anaphylactic shock * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Food allergy * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Infections and infestations     
Abscess limb * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Appendiceal abscess * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Arthritis infective * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Breast abscess * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Bronchitis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Bronchopneumonia * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Cellulitis * 1  1/217 (0.46%)  1 2/659 (0.30%)  2
Erysipelas * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Gastroenteritis * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Groin abscess * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Herpes zoster * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Impetigo * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Influenza * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Kidney infection * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Labyrinthitis * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Latent tuberculosis * 1  2/217 (0.92%)  2 1/659 (0.15%)  1
Localised infection * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Pneumonia * 1  3/217 (1.38%)  3 4/659 (0.61%)  4
Pulmonary tuberculosis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Sepsis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Staphylococcal infection * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Tuberculosis gastrointestinal * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Urosepsis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Wound infection * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Injury, poisoning and procedural complications     
Ankle fracture * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Fall * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Femoral neck fracture * 1  0/217 (0.00%)  0 1/659 (0.15%)  2
Joint dislocation * 1  0/217 (0.00%)  0 2/659 (0.30%)  2
Limb injury * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Lumbar vertebral fracture * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Tendon rupture * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Tibia fracture * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Metabolism and nutrition disorders     
Hyperglycaemia * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Musculoskeletal and connective tissue disorders     
Intervertebral disc degeneration * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Lupus-like syndrome * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Muscle haemorrhage * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Osteoarthritis * 1  0/217 (0.00%)  0 4/659 (0.61%)  4
Rheumatoid nodule * 1  0/217 (0.00%)  0 1/659 (0.15%)  2
Synovial cyst * 1  1/217 (0.46%)  1 1/659 (0.15%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
B-cell lymphoma * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Basal cell carcinoma * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Cervix carcinoma * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Chondrosarcoma * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Endometrial cancer * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Ovarian cancer * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Prostate cancer * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Renal cell carcinoma * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Nervous system disorders     
Carpal tunnel syndrome * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Cerebrovascular accident * 1  1/217 (0.46%)  1 1/659 (0.15%)  1
Cervicobrachial syndrome * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Ischaemic stroke * 1  1/217 (0.46%)  1 1/659 (0.15%)  1
Loss of consciousness * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Migraine * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Renal and urinary disorders     
Bladder outlet obstruction * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Renal failure * 1  1/217 (0.46%)  1 1/659 (0.15%)  1
Reproductive system and breast disorders     
Menorrhagia * 1  0/217 (0.00%)  0 2/659 (0.30%)  4
Uterine polyp * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Epiglottic cyst * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Interstitial lung disease * 1  0/217 (0.00%)  0 2/659 (0.30%)  2
Laryngeal polyp * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Pneumonitis * 1  2/217 (0.92%)  2 0/659 (0.00%)  0
Pulmonary embolism * 1  2/217 (0.92%)  2 1/659 (0.15%)  1
Pulmonary mass * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Respiratory failure * 1  1/217 (0.46%)  1 1/659 (0.15%)  3
Skin and subcutaneous tissue disorders     
Urticaria * 1  1/217 (0.46%)  2 0/659 (0.00%)  0
Surgical and medical procedures     
Coronary arterial stent insertion * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Hip arthroplasty * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Leg amputation * 1  0/217 (0.00%)  0 1/659 (0.15%)  2
Vascular disorders     
Aortic aneurysm * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Aortic stenosis * 1  0/217 (0.00%)  0 1/659 (0.15%)  1
Arteriosclerosis * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
Deep vein thrombosis * 1  1/217 (0.46%)  1 1/659 (0.15%)  1
Orthostatic hypotension * 1  1/217 (0.46%)  1 0/659 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Methotrexate Certolizumab Pegol + Methotrexate
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   63/217 (29.03%)      248/659 (37.63%)    
Gastrointestinal disorders     
Nausea * 1  22/217 (10.14%)  22 83/659 (12.59%)  92
Infections and infestations     
Upper respiratory tract infection * 1  11/217 (5.07%)  12 72/659 (10.93%)  86
Urinary tract infection * 1  16/217 (7.37%)  18 48/659 (7.28%)  63
Nasopharyngitis * 1  13/217 (5.99%)  17 46/659 (6.98%)  60
Investigations     
Alanine aminotransferase increased * 1  9/217 (4.15%)  13 42/659 (6.37%)  46
Nervous system disorders     
Headache * 1  8/217 (3.69%)  11 45/659 (6.83%)  65
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: UCB (Study Director)
Organization: UCB Clinical Trial Call Center
Phone: +1 887 822 9493
Responsible Party: UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier: NCT01519791     History of Changes
Other Study ID Numbers: RA0055 Period 1
2011-001729-25 ( EudraCT Number )
First Submitted: January 19, 2012
First Posted: January 27, 2012
Results First Submitted: July 8, 2015
Results First Posted: September 22, 2015
Last Update Posted: July 31, 2018