Certolizumab Pegol for the Treatment of Patients With Active Rheumatoid Arthritis (REALISTIC)

• American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS)
  
  

• American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS)
  
  
• American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS)
  
  
• American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS)
  
  
• American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS)
  
  
• American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS)
  
  
• American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS)
  
  
• American College of Rheumatology 50% (ACR50) Response at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR50 responders are subjects with at least 50% 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 (PhGADA-VAS)
  
  
• American College of Rheumatology 70% (ACR70) Response at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  ACR70 responders are subjects with at least 70% 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 (PhGADA-VAS)
  
  
• Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity.
  
  
• SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity.
  
  
• CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity.
  
  
• Change From Baseline in Tender Joint Count (TJC) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in Swollen Joint Count (SJC) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in C-reactive Protein (CRP) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  Change from baseline in CRP (mg/L) is computed as the ratio of Week 12 value divided by baseline value. A ratio less then 1 indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
  
  
• Time to Sustained American College of Rheumatology 20% (ACR20) Response [ Time Frame: Baseline up to Week 12 ] [ Designated as safety issue: No ]
  The time from randomization to sustained ACR20 response at 2 consecutive visits (at the latest on Week 12).
  
  
• European League Against Rheumatism (EULAR) Response at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  EULAR response (good response, moderate response, or no response) is defined based on the present value and improvement from baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive protein)].
  
  
• American College of Rheumatology 20% (ACR20) Response at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  ACR20 responders are 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 (PhGADA-VAS). This analysis was carried out using imputation.
  
  
• American College of Rheumatology 50% (ACR50) Response at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  ACR50 responders are subjects with at least 50% 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 (PhGADA-VAS). This analysis was carried out using imputation.
  
  
• American College of Rheumatology 70% (ACR70) Response at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  ACR70 responders are subjects with at least 70% 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 (PhGADA-VAS). This analysis was carried out using imputation.
  
  
• Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. This analysis was carried out using imputation.
  
  
• SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. This analysis was carried out using imputation.
  
  
• CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. This analysis was carried out using imputation.
  
  
• Change From Baseline in Tender Joint Count (TJC) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in Swollen Joint Count (SJC) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in C-reactive Protein (CRP) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  Change from Baseline in CRP (mg/L) is computed as the ratio of the value at Week 28 divided by Baseline value. A ratio less then 1 indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  
• Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
  Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
  
  

The treatment period starts with a 12-week, double-blind, placebo-controlled, randomized period followed by an open-label extension phase. In the double-blind phase, eligible patients are randomized (4:1 ratio) to receive either certolizumab pegol (CZP) or Placebo up to and including Week 10. The randomization will be stratified according to the three factors: concomitant use of methotrexate (MTX, Yes or No), prior anti-tumor necrosis factor (anti-TNF) use (Yes or No), and disease duration categories (< 2 years or ≥ 2 years). From Week 12 all patients remaining in the study receive open-label CZP for a minimum 16 additional weeks until CZP is commercially available.