Rheumatoid Arthritis
Conditions
Keywords
Certolizumab Pegol, Cimzia, Adalimumab, Humira, Rheumatoid Arthritis
Brief summary
This study is conducted to evaluate the short (12 Weeks) and long term (104 Weeks) efficacy of Certolizumab Pegol compared with Adalimumab both in combination with Methotrexate (MTX) in the treatment of moderate to severe Rheumatoid Arthritis (RA) that is not responding adequately to MTX.
Interventions
BIOLOGICALCertolizumab Pegol (CZP)
* Active substance: an injectable volume of 1 ml solution for injection CZP * Pharmaceutical form: prefilled syringes CZP * Concentration: 200 mg/ml CZP * Route of Administration: injections will be given subcutaneously: loading dose of CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal.
BIOLOGICALAdalimumab (ADA)
* Active substance: an injectable volume of 0.8 ml solution for injection ADA * Pharmaceutical form: prefilled syringes ADA * Concentration: 40 mg/0.8 ml ADA * Route of Administration: injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal.
DRUGMethotrexate (MTX)
* Active substance: Methotrexate * Pharmaceutical form: oral tablet * Concentration: 15-25 mg/week * Route of Administration: MTX orally
Sponsors
Parexel
UCB Pharma SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject must have a diagnosis of Rheumatoid Arthritis (RA) at Screening, as defined by the 2010 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria (Aletaha D et al, 2010) * Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti-Cyclic Citrullinated Peptide antibody (anti-CCP) as determined by the central laboratory at Screening * Subject must have moderate to severe RA disease at Screening and Baseline defined as: 1. Screening (all criteria required) * ≥ 4 swollen joints (of 28 prespecified joints) * Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) \> 3.2 * C-Reactive Protein (CRP) concentration ≥ 10 mg/L (or 1.0 mg/dL) or Erythrocyte Sedimentation Rate (ESR) (Westergren) ≥ 28 mm/hr 2. Baseline (both criteria required) * ≥ 4 swollen joints (of 28 prespecified joints) * Disease Activity Score \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) \> 3.2 * Subject must have inadequately responded previously to Methotrexate (MTX) * Subject is using MTX 15 to 25 mg/week orally or subcutaneously at Screening and has used the same MTX regimen for a minimum of 28 days prior to Baseline
Exclusion criteria
* Subject has previously received any biological Disease Modifying Antirheumatic Drug (DMARD) or has received treatment with cyclophosphamide, chlorambucil, Janus Kinase, phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine kinase * Diagnosis of any other inflammatory arthritis * Infected with Tuberculosis (TB) or high risk of acquiring TB infection * Subjects with concurrent acute or chronic viral hepatitis B or C infection * Subjects with a history of chronic or recurrent infections or subjects at high risk of infection * Use of prohibited medications like nonbiological DMARDs (excluding MTX), biological DMARDs excluding study medications, experimental therapy, IA hyaluronic acid
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12 | Week 12 | Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS). |
| Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 | Week 104 | DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6 | Week 6 | DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity. |
| Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 | Week 12 | DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity. |
| Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 | Week 104 | DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity. The definition of Week 12 responders was DAS28\[ESR\] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28\[ESR\] relative to Baseline. |
| Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104 | From Baseline to Week 104 | HAQ-DI was derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), and the total HAQ-DI was scored on the scale of 0-3 as well. Change from Baseline was computed as the value at Week 104 minus the Baseline value. A negative value in Change from Baseline indicates an improvement. |
| Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | From Week 12 up to Week 104 | Response at Week 12 means that a subject had either a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) ≤ 3.2 at Week 12 or had a reduction of DAS28 \[ESR\] ≥ 1.2 from Baseline to Week 12. Kaplan-Meier Estimates of Proportion of Subjects Discontinued are presented per study week (days relative to Week 12 visit). |
| Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12 | Week 104 | DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity. The definition of Week 6/12 responders was DAS28\[ESR\] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28\[ESR\] relative to Baseline. |
| Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6 | Week 6 | Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS). |
Countries
Australia, Austria, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, Ireland, Italy, Mexico, Monaco, Poland, Portugal, Romania, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll patients in December 2011 and concluded in January 2016.
Pre-assignment details
Participant Flow refers to the Randomized Treatment Group (RTG) that consisted of all subjects randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| CZP+MTX (RTG) Subjects received loading doses of CZP 400mg (200mg/PFS, ie, 2 injections) at Baseline, and Weeks 2 and 4; and CZP 200mg at Weeks 6, 8, and 10.
Week 12 Responders continued CZP 200mg at Week 12 and every 2 weeks thereafter through Week 102.
Week 12 Non-Responders were switched to receive ADA 40mg at Week 12 and every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued ADA treatment and were withdrawn from the Treatment Period.
All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously. | 457 |
| ADA+MTX (RTG) Subjects received ADA 40mg (40mg/PFS, ie, 1 injection) at Baseline and then every 2 weeks through Week 10. In order to preserve the blind (ie, use of 2 injections) until Week 12, subjects received an injection of PBO in addition to ADA at Baseline, and Weeks 2 and 4.
Week 12 Responders continued ADA 40mg at Week 12 and every 2 weeks thereafter through Week 102.
Week 12 Non-Responders were switched to a loading dose of CZP 400mg at Weeks 12, 14, and 16 followed by CZP 200mg every 2 weeks through Week 22. At Week 24, Week 12 Non-Responders who did not have DAS28(ESR) LDA or a DAS28(ESR) change from Week 12 reduction of ≥1.2 discontinued CZP treatment and were withdrawn from the Treatment Period.
All subjects received Methotrexate 15 to 25mg/week orally or subcutaneously from Baseline through Week 104. Regimens could have been changed at Week 52 only. Subjects who could not tolerate these doses could receive MTX at a minimum dose of 10mg/week orally or subcutaneously. | 458 |
| Total Title | 915 |
| Total | 1,830 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Week 0 - Week 12 | Adverse event (AE), not fatal | 7 | 8 |
| Week 0 - Week 12 | Exclusion criteria not met | 1 | 0 |
| Week 0 - Week 12 | Investigator decision | 1 | 0 |
| Week 0 - Week 12 | Lack of Efficacy | 0 | 1 |
| Week 0 - Week 12 | Lost to Follow-up | 1 | 1 |
| Week 0 - Week 12 | Other serious disease | 0 | 1 |
| Week 0 - Week 12 | Patient decision | 1 | 0 |
| Week 0 - Week 12 | Personal reason | 0 | 1 |
| Week 0 - Week 12 | Prior history of serious disease | 1 | 0 |
| Week 0 - Week 12 | Protocol Violation | 10 | 16 |
| Week 0 - Week 12 | Protocol violation on screening X-ray | 1 | 0 |
| Week 0 - Week 12 | Sponsor decision | 1 | 0 |
| Week 0 - Week 12 | Withdrawal by Subject | 7 | 2 |
| Week 13 - Week 104 | Abnormal questionable chest X-ray | 0 | 2 |
| Week 13 - Week 104 | Adverse Event | 54 | 54 |
| Week 13 - Week 104 | Death | 2 | 4 |
| Week 13 - Week 104 | Exclusion criteria not met | 1 | 0 |
| Week 13 - Week 104 | False positive test | 1 | 2 |
| Week 13 - Week 104 | Lack of Efficacy | 11 | 12 |
| Week 13 - Week 104 | Lost to Follow-up | 6 | 5 |
| Week 13 - Week 104 | Medical monitor decision | 0 | 2 |
| Week 13 - Week 104 | Non/bad compliance | 7 | 5 |
| Week 13 - Week 104 | Not completed | 0 | 1 |
| Week 13 - Week 104 | Patient declined Safety Follow Up Visit | 1 | 0 |
| Week 13 - Week 104 | Personal reason | 0 | 1 |
| Week 13 - Week 104 | Principal investigator retiring | 1 | 0 |
| Week 13 - Week 104 | Protocol deviation | 1 | 0 |
| Week 13 - Week 104 | Protocol Violation | 6 | 6 |
| Week 13 - Week 104 | Recurrent infections | 1 | 0 |
| Week 13 - Week 104 | Relocation | 0 | 1 |
| Week 13 - Week 104 | Sponsor decision | 0 | 2 |
| Week 13 - Week 104 | Sponsor request | 4 | 0 |
| Week 13 - Week 104 | Week 24 Non-Responder | 20 | 16 |
| Week 13 - Week 104 | Withdrawal by Subject | 22 | 13 |
| Week 13 - Week 104 | Withdrawn in error | 1 | 0 |
Baseline characteristics
| Characteristic | CZP+MTX (RTG) | ADA+MTX (RTG) | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 93 Participants | 85 Participants | 178 Participants |
| Age, Categorical Between 18 and 65 years | 364 Participants | 372 Participants | 736 Participants |
| Age, Continuous Arithmetic mean (standard deviation) | 53.5 years STANDARD_DEVIATION 12.3 | 52.9 years STANDARD_DEVIATION 12.8 | 53.2 years STANDARD_DEVIATION 12.5 |
| Sex: Female, Male Female | 360 Participants | 363 Participants | 723 Participants |
| Sex: Female, Male Male | 97 Participants | 95 Participants | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 269 / 516 | 244 / 523 |
| serious Total, serious adverse events | 67 / 516 | 58 / 523 |
Outcome results
Primary
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104
DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.
Time frame: Week 104
Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP+MTX (FAS) | Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 | 35.5 Percentage of subjects |
| ADA+MTX (FAS) | Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 | 33.5 Percentage of subjects |
p-value: =0.53295% CI: [0.82, 1.45]Regression, Logistic
Primary
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12
Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Time frame: Week 12
Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP+MTX (FAS) | Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12 | 69.2 Percentage of subjects |
| ADA+MTX (FAS) | Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12 | 71.4 Percentage of subjects |
p-value: =0.46795% CI: [0.67, 1.2]Regression, Logistic
Secondary
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104
HAQ-DI was derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), and the total HAQ-DI was scored on the scale of 0-3 as well. Change from Baseline was computed as the value at Week 104 minus the Baseline value. A negative value in Change from Baseline indicates an improvement.
Time frame: From Baseline to Week 104
Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CZP+MTX (FAS) | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104 | -0.62 Units on a Scale | Standard Error 0.03 |
| ADA+MTX (FAS) | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104 | -0.72 Units on a Scale | Standard Error 0.03 |
Secondary
Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12
Response at Week 12 means that a subject had either a Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28 \[ESR\]) ≤ 3.2 at Week 12 or had a reduction of DAS28 \[ESR\] ≥ 1.2 from Baseline to Week 12. Kaplan-Meier Estimates of Proportion of Subjects Discontinued are presented per study week (days relative to Week 12 visit).
Time frame: From Week 12 up to Week 104
Population: Week 12 Responders were defined as those with DAS28(ESR) LDA (defined as DAS28\[ESR\] ≤3.2) or a DAS28(ESR) CFB reduction of ≥1.2 at Week 12.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 13 (Day 7) | 0 proportion of subjects |
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 26 (Day 98) | 0.0198 proportion of subjects |
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 39 (Day 189) | 0.0453 proportion of subjects |
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 52 (Day 280) | 0.0963 proportion of subjects |
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 65 (Day 371) | 0.1643 proportion of subjects |
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 78 (Day 462) | 0.2181 proportion of subjects |
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 91 (Day 553) | 0.2408 proportion of subjects |
| CZP+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 104 (Day 644) | 0.2635 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 104 (Day 644) | 0.2247 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 13 (Day 7) | 0.0028 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 65 (Day 371) | 0.1607 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 26 (Day 98) | 0.0332 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 91 (Day 553) | 0.2105 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 39 (Day 189) | 0.0609 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 78 (Day 462) | 0.1967 proportion of subjects |
| ADA+MTX (FAS) | Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 | Week 52 (Day 280) | 0.0886 proportion of subjects |
Secondary
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12
DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.
Time frame: Week 12
Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP+MTX (FAS) | Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 | 30.4 Percentage of subjects |
| ADA+MTX (FAS) | Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 | 29.7 Percentage of subjects |
Secondary
Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6
DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.
Time frame: Week 6
Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP+MTX (FAS) | Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6 | 20.5 Percentage of subjects |
| ADA+MTX (FAS) | Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6 | 18.1 Percentage of subjects |
Secondary
Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6
Subjects who met the ACR20 criteria were those subjects with at least 20% improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Time frame: Week 6
Population: The Full Analysis Set (FAS) consisted of all subjects who had a valid Baseline and valid post-Baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP+MTX (FAS) | Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6 | 64.5 Percentage of subjects |
| ADA+MTX (FAS) | Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6 | 60.8 Percentage of subjects |
Secondary
Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12
DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity. The definition of Week 6/12 responders was DAS28\[ESR\] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28\[ESR\] relative to Baseline.
Time frame: Week 104
Population: Week 12 Responders were defined as those with DAS28(ESR) LDA (defined as DAS28\[ESR\] ≤3.2) or a DAS28(ESR) CFB reduction of ≥1.2 at Week 12. Only subjects responding at both Week 6 and Week 12 are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP+MTX (FAS) | Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12 | 47.7 Percentage of subjects |
| ADA+MTX (FAS) | Percentage of Subjects With a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in Subjects Responding at Both Week 6 and Week 12 | 46.6 Percentage of subjects |
Secondary
Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104
DAS28 \[ESR\] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity. The definition of Week 12 responders was DAS28\[ESR\] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28\[ESR\] relative to Baseline.
Time frame: Week 104
Population: Week 12 Responders were defined as those with DAS28(ESR) LDA (defined as DAS28\[ESR\] ≤3.2) or a DAS28(ESR) CFB reduction of ≥1.2 at Week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CZP+MTX (FAS) | Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 | 45.6 Percentage of subjects |
| ADA+MTX (FAS) | Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 | 42.4 Percentage of subjects |