Rheumatoid Arthritis
Conditions
Keywords
Certolizumab Pegol - Cimzia, Methotrexate, Rheumatoid Arthritis
Brief summary
This study is intended to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in combination with Methotrexate (MTX) for inducing and sustaining clinical response in the treatment of Disease Modifying Antirheumatic Drug (DMARD)-naïve adults with early active Rheumatoid Arthritis.
Interventions
BIOLOGICALCertolizumab Pegol
Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg at Baseline, Week 2 and Week 4, followed by a maintenance dose of 200 mg every 2 Weeks until Week 50.
OTHERPlacebo
2 syringes Placebo at Baseline, Week 2 and Week 4, followed by 1 syringe Placebo every 2 Weeks.
BIOLOGICALMethotrexate
The MTX treatment is to be initiated at a dose of 10 mg per Week (oral tablets at the strength of 2.5 mg/tablet). 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. Patients who could not tolerate ≥ 15 mg/week MTX by Week 8 were withdrawn while the maximum tolerated dose per patient (optimized dose) was maintained to Week 52.
Sponsors
UCB Pharma SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have a time since diagnosis of adult-onset Rheumatoid Arthritis (RA) less than 1 year as defined by the 2010 ACR/EULAR classification criteria from Screening Visit * Positive Rheumatoid Factor (RF) and/or positive anticyclic Citrullinated Peptide Antibody (anti-CCP) * Active RA disease * DMARD-naïve * Subject is naïve to RA related biologics
Exclusion criteria
* A diagnosis of any other inflammatory Arthritis * History of infected joint prosthesis, or other significant infection and other serious medical condition * Known Tuberculosis (TB) disease or high risk of acquiring TB infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects in Sustained Remission at Week 52 | Week 52 | Sustained remission is defined as a Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) \< 2.6 at both Weeks 40 and 52. DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52 | Week 52 | Sustained LDA is defined as a Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) ≤ 3.2 at both Weeks 40 and 52. |
| Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52 | From Baseline (Week 0) to Week 52 | Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage. |
| Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52 | From Baseline (Week 0) to Week 52 | Radiographic non-progression is defined as change in mTSS ≤ 0.5. |
| Change From Baseline in the Joint Erosion Score to Week 52 | 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. |
| Change From Baseline in the Joint Narrowing Score to Week 52 | 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. |
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52 | 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). |
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52 | 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). |
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52 | 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). |
| Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52 | 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. |
| Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52 | 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. |
| Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52 | 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. |
| Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52 | 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. |
| 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 | 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. |
| Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52 | From Baseline (Week 0) to Week 52 | Good response is defined as: DAS28\[ESR\] ≤ 3.2 and decrease from Baseline by \> 1.2; moderate response is defined as achievement of one of the following: * DAS28\[ESR\] ≤ 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2 * DAS28\[ESR\] \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6 * DAS28\[ESR\] \> 5.1 and decrease from Baseline \>1.2. |
| Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52 | From Baseline (Week 0) to 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. A negative value in DAS28\[ESR\] change from Baseline indicates an improvement from Baseline. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52 | From Baseline (Week 0) to 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. The CDAI score ranges from 0 to 76, with a negative value in CDAI change from Baseline indicating an improvement from Baseline. |
| Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52 | From Baseline (Week 0) to 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. The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline. |
| Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52 | 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. |
| Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52 | 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. |
| Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52 | 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. |
| Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | Week 52 | Number of work days missed in the last month for employed subjects. |
| Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | Week 52 | Number of work days with reduced productivity in the last month for employed subjects. |
| Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 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. |
| Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | Week 52 | Number of days with no household work in the last month. |
| Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | Week 52 | Number of days with reduced household work productivity in the last month. |
| Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | Week 52 | Number of days with hired outside help in the last month. |
| Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | Week 52 | Number of days missed of family/social/leisure activities in the last month. |
| Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 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). |
| Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52 | Week 52 | LDA is defined as achieving a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) ≤ 3.2. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Colombia, Czechia, France, Germany, Hungary, Ireland, Italy, Mexico, Monaco, Netherlands, Poland, Romania, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORUCB Clinical Trial Call Center
+1 877 822 9493 (UCB)
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 219 |
| 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. | 660 |
| Total Title | 879 |
| Total | 1,758 |
Baseline characteristics
| Characteristic | Placebo + Methotrexate | Certolizumab Pegol + Methotrexate | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 36 Participants | 98 Participants | 134 Participants |
| Age, Categorical Between 18 and 65 years | 182 Participants | 560 Participants | 742 Participants |
| Age, Continuous | 51.3 years STANDARD_DEVIATION 13.2 | 50.5 years STANDARD_DEVIATION 13.6 | 50.7 years STANDARD_DEVIATION 13.5 |
| Sex: Female, Male Female | 175 Participants | 499 Participants | 674 Participants |
| Sex: Female, Male Male | 44 Participants | 161 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 63 / 217 | 248 / 659 |
| serious Total, serious adverse events | 20 / 217 | 70 / 659 |
Outcome results
Primary
Percentage of Subjects in Sustained Remission at Week 52
Sustained remission is defined as a Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) \< 2.6 at both Weeks 40 and 52. DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects in Sustained Remission at Week 52 | 15.0 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects in Sustained Remission at Week 52 | 28.9 percentage of subjects |
Comparison: 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 52p-value: <0.00195% CI: [1.503, 3.468]Regression, Logistic
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI) to 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. 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
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 CDAI values were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52 | -29.09 units on a scale | Standard Error 0.84 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52 | -33.11 units on a scale | Standard Error 0.52 |
Secondary
Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to 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. A negative value in DAS28\[ESR\] change from Baseline indicates an improvement from Baseline.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52 | -3.615 units on a scale | Standard Error 0.069 |
Secondary
Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52
Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52 | 1.8 units on a scale | Standard Deviation 4.3 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52 | 0.2 units on a scale | Standard Deviation 3.2 |
Comparison: 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 52p-value: <0.00195% CI: [-1.005, -0.5]ANCOVA on ranks
Secondary
Change From Baseline in Simplified Disease Activity Index (SDAI) to 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. 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
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 SDAI values were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52 | -30.24 units on a scale | Standard Error 0.88 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52 | -34.55 units on a scale | Standard Error 0.55 |
Secondary
Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52
BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue). A negative value in BRAF-MDQ change from Baseline indicates an improvement from Baseline.
Time frame: 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 BRAF-MDQ values were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52 | -17.8 units on a scale | Standard Error 0.6 |
Secondary
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52
The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. The total score ranges from 0 (no difficulty) to 3 (unable to do) with lower scores meaning lower disability. A negative value in HAQ-DI change from Baseline indicates an improvement from Baseline.
Time frame: 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 HAQ-DI values were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52 | -0.997 units on a scale | Standard Error 0.028 |
Comparison: 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 52p-value: <0.00195% CI: [-0.273, -0.082]ANCOVA
Secondary
Change From Baseline in the Joint Erosion Score to Week 52
Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions. The maximum possible erosion score for all 32-hand joints was 160. The maximum possible erosion score for all 12 feet joints was 120. Thus, the maximum possible total erosion score for hands and feet was 280.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Change From Baseline in the Joint Erosion Score to Week 52 | 1.1 units on a scale | Standard Deviation 3 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in the Joint Erosion Score to Week 52 | 0.1 units on a scale | Standard Deviation 2.1 |
Secondary
Change From Baseline in the Joint Narrowing Score to Week 52
Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The maximum possible score for JSN in all 30 hand joints was 120. The maximum possible score for JSN in all 12 feet joints was 48. Thus, the maximum possible total JSN score for Hands and feet was 168.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Change From Baseline in the Joint Narrowing Score to Week 52 | 0.7 units on a scale | Standard Deviation 2.3 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Change From Baseline in the Joint Narrowing Score to Week 52 | 0.1 units on a scale | Standard Deviation 1.7 |
Secondary
Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 1.9 units on a scale | Standard Deviation 2.5 |
Secondary
Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference) for employed subjects.
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 1.9 units on a scale | Standard Deviation 2.3 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 1.4 units on a scale | Standard Deviation 2 |
Secondary
Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Number of days missed of family/social/leisure activities in the last month.
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 0.9 days | Standard Deviation 3.6 |
Secondary
Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Number of days with hired outside help in the last month.
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 0.7 days | Standard Deviation 3.3 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 0.6 days | Standard Deviation 3.2 |
Secondary
Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Number of days with no household work in the last month.
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 3.0 days | Standard Deviation 6.7 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 1.9 days | Standard Deviation 5.1 |
Secondary
Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Number of days with reduced household work productivity in the last month.
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 2.1 days | Standard Deviation 5.3 |
Secondary
Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Number of work days missed in the last month for employed subjects.
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 0.9 days | Standard Deviation 2.5 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 0.6 days | Standard Deviation 2.6 |
Secondary
Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52
Number of work days with reduced productivity in the last month for employed subjects.
Time frame: 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 WPS-RA values were imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 1.8 days | Standard Deviation 4.7 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 | 1.0 days | Standard Deviation 3.4 |
Secondary
Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52
Good response is defined as: DAS28\[ESR\] ≤ 3.2 and decrease from Baseline by \> 1.2; moderate response is defined as achievement of one of the following: * DAS28\[ESR\] ≤ 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2 * DAS28\[ESR\] \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6 * DAS28\[ESR\] \> 5.1 and decrease from Baseline \>1.2.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52 | 82.2 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52 | 89.9 percentage of subjects |
Secondary
Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52
LDA is defined as achieving a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) ≤ 3.2.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52 | 39.4 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52 | 54.7 percentage of subjects |
Secondary
Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52
Sustained LDA is defined as a Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) ≤ 3.2 at both Weeks 40 and 52.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52 | 28.6 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52 | 43.8 percentage of subjects |
Comparison: 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 52p-value: <0.00195% CI: [1.384, 2.767]Regression, Logistic
Secondary
Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52
The ACR/EULAR 2011 remission criteria is defined as: Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1, C-reactive protein (CRP) ≤ 1 mg/dl and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52 | 32.4 percentage of subjects |
Secondary
Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice at Week 52
The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as: Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | 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 |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | 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 | 35.3 percentage of subjects |
Secondary
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52
The assessments are based on a 20 % or greater improvement from Baseline in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time frame: From Baseline (Week 0) to 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52 | 61.5 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52 | 69.0 percentage of subjects |
Secondary
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52
The assessments are based on a 50 % or greater improvement from Baseline in the number of tender joints, a 50 %, or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time frame: From Baseline (Week 0) to 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52 | 52.6 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52 | 61.8 percentage of subjects |
Comparison: 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 52p-value: =0.02395% CI: [1.052, 1.989]Regression, Logistic
Secondary
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52
The assessments are based on a 70 % or greater improvement from Baseline in the number of tender joints, a 70 %, or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time frame: From Baseline (Week 0) to 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52 | 39.9 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52 | 51.3 percentage of subjects |
Secondary
Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52
Normative physical function is defined as HAQ-DI score ≤ 0.5. The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. The total score ranges from 0 to 3 with lower scores meaning lower disability.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52 | 35.7 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52 | 48.1 percentage of subjects |
Secondary
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52 | 26.3 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52 | 38.9 percentage of subjects |
Secondary
Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52 | 26.8 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52 | 42.6 percentage of subjects |
Secondary
Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52
Radiographic non-progression is defined as change in mTSS ≤ 0.5.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52 | 49.7 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52 | 70.3 percentage of subjects |
Secondary
Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Methotrexate (Full Analysis Set) | Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52 | 24.9 percentage of subjects |
| Certolizumab Pegol + Methotrexate (Full Analysis Set) | Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52 | 38.9 percentage of subjects |