Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Joint Disease, Arthritis, Certolizumab pegol, Cimzia
Brief summary
During the run-in period, CZP will be administered at 400 mg (2 injections) at Wks 0, 2, and 4 and 200 mg with placebo (1 injection placebo, 1 injection CZP) at Wks 6, 8, 10, 12, 14 and 16. At Wk 18 patients will be grouped as responders or non-responders based on results of the ACR20 at Week 16.
Detailed description
Subjects with a stable methotrexate (MTX) dose enter the run-in period in which certolizumab pegol (CZP) will be administered at a dose of 400 mg (2 injections) at Weeks 0, 2, and 4 and at a dose of 200 mg with placebo (1 injection placebo, 1 injection CZP) at Weeks 6, 8, 10, 12, 14 and 16. The dose of MTX should be stable for at least 2 months prior to the Baseline visit and will remain stable throughout the trial, unless there is a need to reduce the dose for reasons of toxicity. At the Week 18 visit, subjects who were ACR20 (American College of Rheumatology 20% Improvement) responders at Week 16 will be randomized in a double-blinded way to receive either 400 mg CZP given every 4 weeks and placebo given every 4 weeks given as two injections (alternating CZP and placebo every two weeks) plus MTX, 200 mg CZP and placebo administered every 2 weeks (one injection of each) plus MTX, or Placebo administered as two injections every 2 weeks plus MTX. Non-responders will be withdrawn from the study.
Interventions
DRUGCertolizumab pegol
400 mg certolizumab pegol given every 4 weeks and placebo given every 4 weeks given as two injections (alternating injections every two weeks)
OTHERPlacebo
placebo (saline) administered as two injections every 2 weeks
Sponsors
UCB Pharma
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
* Patients with established adult rheumatoid arthritis currently on Methotrexate for at least 3 months
Exclusion criteria
* All concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment * Previous clinical trials participation and previous biological therapy that could interfere with the results of the present clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | PCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from 1 to 81, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | MCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from -9 to 82, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Change from Baseline in Patient's Assessment of Arthritis Pain-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 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Change from Baseline in Patient's Global Assessment of Disease Activity-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18. | Week 18 up to Week 34 | ACR20 loss are subjects with \<20% improvement from Baseline for tender joint count, swollen joint count, and at least 3/5 core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein, 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale at 2 consecutive visits. Subjects losing response for 2 consecutive visits are considered as having the event on the day of the visit where response was first lost. |
| Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 16 in All Patients | Baseline, Week 16 | 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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. \< 2.6 Remission, \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High |
| Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 16 in All Patients | Baseline, Week 16 | 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI) |
| Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 16 in All Patients | Baseline, Week 16 | 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI) |
| Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 16 in All Patients | Baseline, Week 16 | 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI) |
| Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 16 in All Patients | Baseline, Week 16 | 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. \<= 3.3 Remission, \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High |
| Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 16 in All Patients | Baseline, Week 16 | 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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. The range for the CDAI is 0 - 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. |
| DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 16 in All Patients | Week 16 | 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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \< 2.6 (Remission), \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High |
| SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 16 in All Patients | Week 16 | 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \<= 3.3 (Remission), \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High |
| CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 16 in All Patients | Week 16 | 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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). The range for the CDAI is 0 - 76 with a lower CDAI score indicating approvement in activity and a higher score indicating a decline activity. |
| Ratio From Baseline in CRP (C-reactive Protein) Level at Week 16 in All Patients | Baseline, Week 16 | Ratio is defined as the CRP value at Week 16 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 16 in All Patients | Baseline, Week 16 | 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). Thus, the mean also has a range from 0-3. Change from baseline is computed as the value at Week 16 minus the 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. |
| Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI) |
| Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | 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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI) |
| Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | 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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward. \< 2.6 Remission, \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High |
| Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. \<= 3.3 Remission, \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High |
| Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | 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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. Range for CDAI is 0-76 with a lower CDAI score reflects approvement in activity and a higher score reflects a decline. |
| DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18 | Week 34 | 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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \< 2.6 (Remission), \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High |
| SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18 | Week 34 | 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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \<= 3.3 (Remission), \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High |
| CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18 | Week 34 | 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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). The range for the CDAI is 0 - 76 with a lower CDAI score indicating approvement in activity and a higher score indicating a decline activity. |
| Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Ratio is defined as the CRP value at Week 34 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method with an ANCOVA model on observed log transformed data with factors treatment and log transformed Baseline CRP level. The number presented is the geometric least squares mean with it's 95% confidence interval. |
| Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | 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). Thus, the mean also has a range from 0-3. Change from baseline is computed as the value at Week 34 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Change from Baseline in Fatigue Assessment scale (0 to 10, 0 is No Fatigue and 10 is Fatigue as bad as you can imagine) is computed as the value at Week 34 minus the Baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PhGADA (Physician's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Change from Baseline in Physician's Global Assessment of Disease Activity-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in TJC (Tender Joint Count) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Change from Baseline in Tender Joint Count is computed as the value at Week 34 minus the Baseline value (28 joints were assessed at each visit). A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Change From Baseline in SJC (Swollen Joint Count) at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Change from Baseline in Swollen Joint Count is computed as the value at Week 34 minus the Baseline value (28 joints were assessed at each visit). A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. |
| Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 16 in All Patients | Baseline, Week 16 | Ratio is defined as the ESR value at Week 16 divided by the ESR value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 34 in Patients Randomized at Week 18 | Baseline, Week 34 | Ratio is defined as the ESR value at Week 34 divided by the ESR value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method with an ANCOVA model on observed log transformed data with factors treatment and log transformed Baseline CRP level. The number presented is the geometric least squares mean with it's 95% confidence interval. |
Countries
Canada, France, United States
Participant flow
Recruitment details
The study started in December 2007 with subjects from Canada, France, and United States. The primary completion date occurred in December 2010, with study completion in March 2011.
Participants by arm
| Arm | Count |
|---|---|
| Run-in Overall Overall includes all 333 subjects that entered the Run-in period of the study | 333 |
| Total | 333 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind | Adverse Event | 0 | 3 | 4 | 1 |
| Double-Blind | Loss of Efficacy | 0 | 1 | 2 | 10 |
| Double-Blind | Lost to Follow-up | 0 | 1 | 0 | 2 |
| Double-Blind | Other: Discontinued Methotrexate | 0 | 1 | 0 | 0 |
| Double-Blind | Other: Forbidden Medication | 0 | 0 | 1 | 0 |
| Double-Blind | Withdrawal by Subject | 0 | 1 | 2 | 2 |
| Run-in | Adverse Event | 17 | 0 | 0 | 0 |
| Run-in | Lack of Efficacy | 93 | 0 | 0 | 0 |
| Run-in | Loss of Efficacy | 1 | 0 | 0 | 0 |
| Run-in | Lost to Follow-up | 4 | 0 | 0 | 0 |
| Run-in | Other: Did Not Meet Joint Count Criteria | 1 | 0 | 0 | 0 |
| Run-in | Other: Exclusionary Lab Value | 1 | 0 | 0 | 0 |
| Run-in | Other: Per Sponsor Request | 2 | 0 | 0 | 0 |
| Run-in | Withdrawal by Subject | 5 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Run-in Overall |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 69 Participants |
| Age, Categorical Between 18 and 65 years | 264 Participants |
| Age, Continuous | 54.2 years STANDARD_DEVIATION 12.75 |
| Region of Enrollment Canada | 20 participants |
| Region of Enrollment France | 7 participants |
| Region of Enrollment United States | 306 participants |
| Sex: Female, Male Female | 253 Participants |
| Sex: Female, Male Male | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 80 / 333 | 20 / 69 | 12 / 70 | 27 / 69 |
| serious Total, serious adverse events | 18 / 333 | 2 / 69 | 5 / 70 | 0 / 69 |
Outcome results
Primary
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 65.2 percentage of subjects |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 67.1 percentage of subjects |
| Placebo + Methotrexate | Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 44.9 percentage of subjects |
Secondary
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 16 in All Patients
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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). The range for the CDAI is 0 - 76 with a lower CDAI score indicating approvement in activity and a higher score indicating a decline activity.
Time frame: Week 16
Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 16 in All Patients | 17.1 percentage of subjects |
Secondary
CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18
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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). The range for the CDAI is 0 - 76 with a lower CDAI score indicating approvement in activity and a higher score indicating a decline activity.
Time frame: Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18 | 27.5 percentage of subjects |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18 | 21.4 percentage of subjects |
| Placebo + Methotrexate | CDAI (Clinical Disease Activity Index) Remission (CDAI ≤2.8) at Week 34 in Patients Randomized at Week 18 | 15.9 percentage of subjects |
Secondary
Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 12.95 units on a scale | Standard Error 1.042 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 11.28 units on a scale | Standard Error 1.044 |
| Placebo + Methotrexate | Change From Baseline in Bodily Pain (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 6.12 units on a scale | Standard Error 1.047 |
Secondary
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 16 in All Patients
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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. The range for the CDAI is 0 - 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity.
Time frame: Baseline, Week 16
Population: Of the 333 subjects in the Run-in period, 328 are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 16 in All Patients | -23.3 units on a scale | Standard Deviation 13.2 |
Secondary
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18
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 (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. Range for CDAI is 0-76 with a lower CDAI score reflects approvement in activity and a higher score reflects a decline.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 70 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | -29.06 units on a scale | Standard Error 1.509 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | -27.14 units on a scale | Standard Error 1.498 |
| Placebo + Methotrexate | Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | -17.03 units on a scale | Standard Error 1.536 |
Secondary
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 16 in All Patients
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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. \< 2.6 Remission, \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High
Time frame: Baseline, Week 16
Population: Of the 333 subjects in the Run-in period, 325 are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 16 in All Patients | -2.3 units on a scale | Standard Deviation 1.3 |
Secondary
Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18
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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward. \< 2.6 Remission, \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 204 subjects (69 400 mg CZP, 68 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18 | -3.04 units on a scale | Standard Error 0.163 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18 | -2.83 units on a scale | Standard Error 0.164 |
| Placebo + Methotrexate | Change From Baseline in DAS28 (Disease Activity Score-28 Items) at Week 34 in Patients Randomized at Week 18 | -1.65 units on a scale | Standard Error 0.166 |
Secondary
Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18
Change from Baseline in Fatigue Assessment scale (0 to 10, 0 is No Fatigue and 10 is Fatigue as bad as you can imagine) is computed as the value at Week 34 minus the Baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 70 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18 | -2.39 units on a scale | Standard Error 0.261 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18 | -3.03 units on a scale | Standard Error 0.258 |
| Placebo + Methotrexate | Change From Baseline in Fatigue Assessment Scale (FAS) at Week 34 in Patients Randomized at Week 18 | -1.33 units on a scale | Standard Error 0.264 |
Secondary
Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 5.46 units on a scale | Standard Error 0.959 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 5.51 units on a scale | Standard Error 0.956 |
| Placebo + Methotrexate | Change From Baseline in General Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 3.16 units on a scale | Standard Error 0.961 |
Secondary
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 16 in All Patients
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). Thus, the mean also has a range from 0-3. Change from baseline is computed as the value at Week 16 minus the 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 frame: Baseline, Week 16
Population: Of the 333 subjects in the Run-in period, 330 are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 16 in All Patients | -0.5 units on a scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18
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). Thus, the mean also has a range from 0-3. Change from baseline is computed as the value at Week 34 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18 | -0.64 units on a scale | Standard Error 0.06 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18 | -0.72 units on a scale | Standard Error 0.06 |
| Placebo + Methotrexate | Change From Baseline in HAQ-DI (Health Assessment Questionnaire-Disability Index) Score at Week 34 in Patients Randomized at Week 18 | -0.38 units on a scale | Standard Error 0.061 |
Secondary
Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18
MCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from -9 to 82, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 202 subjects (66 400 mg CZP, 68 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18 | 5.51 units on a scale | Standard Error 1.162 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18 | 8.59 units on a scale | Standard Error 1.147 |
| Placebo + Methotrexate | Change From Baseline in MCS (Short Form 36-item Health Survey Mental Component Summary) at Week 34 in Patients Randomized at Week 18 | 4.90 units on a scale | Standard Error 1.143 |
Secondary
Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 5.38 units on a scale | Standard Error 1.05 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 7.44 units on a scale | Standard Error 1.042 |
| Placebo + Methotrexate | Change From Baseline in Mental Health (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 4.13 units on a scale | Standard Error 1.049 |
Secondary
Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18
Change from Baseline in Patient's Assessment of Arthritis Pain-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 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18 | -36.41 units on a scale | Standard Error 2.894 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18 | -34.33 units on a scale | Standard Error 2.869 |
| Placebo + Methotrexate | Change From Baseline in PAAP (Patient's Assessment of Arthritis Pain) at Week 34 in Patients Randomized at Week 18 | -17.47 units on a scale | Standard Error 2.911 |
Secondary
Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18
PCS norm-based scores are calculated based upon the following 8 domain scores, Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, and range from 1 to 81, where 50 represents the normative value. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 202 subjects (66 400 mg CZP, 68 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18 | 10.54 units on a scale | Standard Error 0.939 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18 | 9.65 units on a scale | Standard Error 0.928 |
| Placebo + Methotrexate | Change From Baseline in PCS (Short Form 36-item Health Survey Physical Component Summary) at Week 34 in Patients Randomized at Week 18 | 5.09 units on a scale | Standard Error 0.926 |
Secondary
Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 8.39 units on a scale | Standard Error 1.08 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 9.07 units on a scale | Standard Error 1.076 |
| Placebo + Methotrexate | Change From Baseline in Physical Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 4.09 units on a scale | Standard Error 1.086 |
Secondary
Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18
Change from Baseline in Patient's Global Assessment of Disease Activity-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | -35.58 units on a scale | Standard Error 2.966 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | -33.07 units on a scale | Standard Error 2.946 |
| Placebo + Methotrexate | Change From Baseline in PtGADA (Patient's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | -16.37 units on a scale | Standard Error 2.987 |
Secondary
Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 204 subjects (67 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 6.86 units on a scale | Standard Error 1.322 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 8.86 units on a scale | Standard Error 1.313 |
| Placebo + Methotrexate | Change From Baseline in Role Emotional (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 5.86 units on a scale | Standard Error 1.306 |
Secondary
Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 9.80 units on a scale | Standard Error 1.095 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 11.06 units on a scale | Standard Error 1.097 |
| Placebo + Methotrexate | Change From Baseline in Role Physical (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 7.14 units on a scale | Standard Error 1.099 |
Secondary
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 16 in All Patients
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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. \<= 3.3 Remission, \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High
Time frame: Baseline, Week 16
Population: Of the 333 subjects in the Run-in period, 326 are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 16 in All Patients | -24.1 units on a scale | Standard Deviation 13.5 |
Secondary
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18
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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score. \<= 3.3 Remission, \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 70 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | -30.46 units on a scale | Standard Error 1.554 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | -28.15 units on a scale | Standard Error 1.532 |
| Placebo + Methotrexate | Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 34 in Patients Randomized at Week 18 | -17.35 units on a scale | Standard Error 1.571 |
Secondary
Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 8.87 units on a scale | Standard Error 1.179 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 10.03 units on a scale | Standard Error 1.17 |
| Placebo + Methotrexate | Change From Baseline in Social Functioning (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 6.42 units on a scale | Standard Error 1.187 |
Secondary
Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18
There are 8 SF-36 domain scores: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health, each ranging from 0 to 100, with higher scores indicating better health. A larger positive value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (68 400 mg CZP, 69 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 9.88 units on a scale | Standard Error 1.127 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 11.53 units on a scale | Standard Error 1.123 |
| Placebo + Methotrexate | Change From Baseline in Vitality (Short Form 36-item Health Survey Domain) at Week 34 in Patients Randomized at Week 18 | 5.47 units on a scale | Standard Error 1.129 |
Secondary
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 16 in All Patients
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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \< 2.6 (Remission), \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High
Time frame: Week 16
Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 16 in All Patients | 17.7 percentage of subjects |
Secondary
DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18
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 (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \< 2.6 (Remission), \> = 2.6 - \< =3.2 Low, \> 3.2 - \< = 5.1 Moderate, \> 5.1 High
Time frame: Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18 | 29.0 percentage of subjects |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18 | 18.6 percentage of subjects |
| Placebo + Methotrexate | DAS28 (Disease Activity Score-28 Items) Remission (DAS28 <2.6) at Week 34 in Patients Randomized at Week 18 | 5.8 percentage of subjects |
Secondary
Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18.
ACR20 loss are subjects with \<20% improvement from Baseline for tender joint count, swollen joint count, and at least 3/5 core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein, 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale at 2 consecutive visits. Subjects losing response for 2 consecutive visits are considered as having the event on the day of the visit where response was first lost.
Time frame: Week 18 up to Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18. | NA days |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18. | NA days |
| Placebo + Methotrexate | Median Time to Loss of ACR20 (American College of Rheumatology 20% Improvement) Response After Week 18 in Patients Randomized at Week 18. | 98.0 days |
Secondary
Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 16 in All Patients
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Time frame: Baseline, Week 16
Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Percentage of ACR20 (American College of Rheumatology 20% Improvement) Responders at Week 16 in All Patients | 61.3 percentage of subjects |
Secondary
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 16 in All Patients
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Time frame: Baseline, Week 16
Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 16 in All Patients | 37.8 percentage of subjects |
Secondary
Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 52.2 percentage of subjects |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 50.0 percentage of subjects |
| Placebo + Methotrexate | Percentage of ACR50 (American College of Rheumatology 50% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 30.4 percentage of subjects |
Secondary
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 16 in All Patients
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Time frame: Baseline, Week 16
Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 16 in All Patients | 16.2 percentage of subjects |
Secondary
Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18
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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. Missing values were imputed using Non-Responder Imputation (NRI)
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 37.7 percentage of subjects |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 30.0 percentage of subjects |
| Placebo + Methotrexate | Percentage of ACR70 (American College of Rheumatology 70% Improvement) Responders at Week 34 in Patients Randomized at Week 18 | 15.9 percentage of subjects |
Secondary
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 16 in All Patients
Ratio is defined as the CRP value at Week 16 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 16
Population: Of the 333 subjects in the Run-in period, 330 are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Ratio From Baseline in CRP (C-reactive Protein) Level at Week 16 in All Patients | 0.5 Ratio | Geometric Coefficient of Variation 122.6 |
Secondary
Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18
Ratio is defined as the CRP value at Week 34 divided by the CRP value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method with an ANCOVA model on observed log transformed data with factors treatment and log transformed Baseline CRP level. The number presented is the geometric least squares mean with it's 95% confidence interval.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18 | 0.44 Ratio |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18 | 0.48 Ratio |
| Placebo + Methotrexate | Ratio From Baseline in CRP (C-reactive Protein) Level at Week 34 in Patients Randomized at Week 18 | 0.82 Ratio |
Secondary
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 16 in All Patients
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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \<= 3.3 (Remission), \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High
Time frame: Week 16
Population: Since Non-Response Imputation (NRI) was used, all 333 subjects in the run-in period are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 16 in All Patients | 15.9 percentage of subjects |
Secondary
SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18
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 Disease Activity - Visual Analog Scale (VAS in cm), and Investigator's Global Assessment of Disease Activity - Visual Analog Scale (VAS in cm). 28 joints are examined where a lower score indicates less disease activity. Missing values were imputed using Non-Responder Imputation (NRI). \<= 3.3 (Remission), \> 3.3 - \<= 11 Low, \> 11 - \<= 26 Moderate, \> 26 High
Time frame: Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 208 subjects (69 400 mg CZP, 70 200 mg CZP, 69 placebo) are included in this analysis which uses Non-Response Imputation (NRI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18 | 29.0 percentage of subjects |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18 | 17.1 percentage of subjects |
| Placebo + Methotrexate | SDAI (Simplified Disease Activity Index) Remission (SDAI ≤3.3) at Week 34 in Patients Randomized at Week 18 | 13.0 percentage of subjects |
Other Pre-specified
Change From Baseline in PhGADA (Physician's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18
Change from Baseline in Physician's Global Assessment of Disease Activity-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 34 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 206 subjects (69 400 mg CZP, 70 200 mg CZP, 67 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in PhGADA (Physician's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | -44.62 units on a scale | Standard Error 2.428 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in PhGADA (Physician's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | -40.24 units on a scale | Standard Error 2.427 |
| Placebo + Methotrexate | Change From Baseline in PhGADA (Physician's Global Assessment of Disease Activity) at Week 34 in Patients Randomized at Week 18 | -25.97 units on a scale | Standard Error 2.476 |
Other Pre-specified
Change From Baseline in SJC (Swollen Joint Count) at Week 34 in Patients Randomized at Week 18
Change from Baseline in Swollen Joint Count is computed as the value at Week 34 minus the Baseline value (28 joints were assessed at each visit). A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in SJC (Swollen Joint Count) at Week 34 in Patients Randomized at Week 18 | -9.29 Joints | Standard Error 0.542 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in SJC (Swollen Joint Count) at Week 34 in Patients Randomized at Week 18 | -8.37 Joints | Standard Error 0.54 |
| Placebo + Methotrexate | Change From Baseline in SJC (Swollen Joint Count) at Week 34 in Patients Randomized at Week 18 | -5.41 Joints | Standard Error 0.547 |
Other Pre-specified
Change From Baseline in TJC (Tender Joint Count) at Week 34 in Patients Randomized at Week 18
Change from Baseline in Tender Joint Count is computed as the value at Week 34 minus the Baseline value (28 joints were assessed at each visit). A negative value in change from Baseline indicates an improvement. This analysis was carried out using an ANCOVA model on Last Observation Carried Forward (LOCF) data with factors treatment and Baseline score.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 207 subjects (69 400 mg CZP, 70 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Change From Baseline in TJC (Tender Joint Count) at Week 34 in Patients Randomized at Week 18 | -11.81 Joints | Standard Error 0.702 |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Change From Baseline in TJC (Tender Joint Count) at Week 34 in Patients Randomized at Week 18 | -11.33 Joints | Standard Error 0.692 |
| Placebo + Methotrexate | Change From Baseline in TJC (Tender Joint Count) at Week 34 in Patients Randomized at Week 18 | -7.16 Joints | Standard Error 0.707 |
Other Pre-specified
Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 16 in All Patients
Ratio is defined as the ESR value at Week 16 divided by the ESR value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 16
Population: Of the 333 subjects in the Run-in period, 328 are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 16 in All Patients | 0.6 Ratio | Geometric Coefficient of Variation 76.7 |
Other Pre-specified
Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 34 in Patients Randomized at Week 18
Ratio is defined as the ESR value at Week 34 divided by the ESR value at Baseline. This analysis was carried out using the Last Observation Carried Forward (LOCF) method with an ANCOVA model on observed log transformed data with factors treatment and log transformed Baseline CRP level. The number presented is the geometric least squares mean with it's 95% confidence interval.
Time frame: Baseline, Week 34
Population: Of the 208 subjects in the Full Analysis Set (FAS) 205 subjects (69 400 mg CZP, 68 200 mg CZP, 68 placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Certolizumab Pegol 400 mg and Placebo + Methotrexate | Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 34 in Patients Randomized at Week 18 | 0.56 Ratio |
| Certolizumab Pegol 200 mg and Placebo + Methotrexate | Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 34 in Patients Randomized at Week 18 | 0.62 Ratio |
| Placebo + Methotrexate | Ratio From Baseline in ESR (Erythrocyte Sedimentation Rate) Level at Week 34 in Patients Randomized at Week 18 | 0.84 Ratio |