Rheumatoid Arthritis
Conditions
Keywords
Cimzia®, CDP870, CZP, Certolizumab Pegol, Rheumatoid Arthritis, MRI
Brief summary
Phase IIIb study to determine early response to Certolizumab Pegol (CZP) with Magnetic Resonance Imaging (MRI) score Outcome Measures in Rheumatoid Arthritis (RA) Clinical Trials (OMERACT) RA MRI Scoring System (RAMRIS) in subjects with RA.
Detailed description
To identify the efficacy of Certolizumab Pegol (CZP) on synovitis in dynamic MRI parameters; to make the correlation between European League Against Rheumatism (EULAR), American College of Rheumatology (ACR)p, Disease Activity Score-28 (DAS 28) responses, and Digital XRay (DXR) assessment with reduction of synovitis.
Interventions
OTHERPlacebo
Placebo provided for the first subcutaneous injection in single-use vials at Week 0 (2 vials required), then Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4 and 6, followed by Certolizumab Pegol (CZP) 200 mg every 2 weeks from Week 8 to Week 40
BIOLOGICALCertolizumab Pegol (CZP) 200 mg
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
BIOLOGICALCertolizumab Pegol (CZP) 400 mg
Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of adult-onset Rheumatoid Arthritis (RA) of at least 3 months duration but no longer than 15 years * Subjects with an active adult Rheumatoid Arthritis disease * Subjects who have been on Disease-Modifying Anti-Rheumatic Drug (DMARD) therapy for at least 12 weeks
Exclusion criteria
* Subject must not have a secondary, non-inflammatory type of musculoskeletal condition (eg, osteoarthritis or fibromyalgia) that in the investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject's primary diagnosis of Rheumatoid Arthritis (RA) * Subject must not have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis or ankylosing spondylitis) * Subject must not have a history of an infected joint prosthesis at any time with prosthesis still in situ * Subject must not have received more than 1 biological agent * Subject must not have a history of lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time * Subject with known Tuberculosis (TB) disease, high risk of acquiring TB infection or latent TB infection * Subject must not have a known hypersensitivity to any components of the investigational medicinal product * Subject must not have contraindications for Magnetic Resonance Image (MRI) and contrast agent * Subject must not have any other condition which, in the investigator's judgement, would make them unsuitable for inclusion in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 16 Compared to Baseline for Certolizumab Pegol Arm | From Baseline to Week 16 | Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement. |
| Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 8 Compared to Baseline for Certolizumab Pegol Arm | From Baseline to Week 8 | Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement. |
| Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 4 Compared to Baseline for Certolizumab Pegol Arm | From Baseline to Week 4 | Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement. |
| Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 2 Compared to Baseline for Certolizumab Pegol Arm | From Baseline to Week 2 | Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement. |
| Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 1 Compared to Baseline for Certolizumab Pegol Arm | From Baseline to Week 1 | Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16 | From Baseline to Week 16 | Subjects who meet the ACR50 criteria are those 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 (PhGA-VAS). |
| Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16 | From Baseline to Week 16 | Subjects who meet the ACR70 criteria are those 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 (PhGA-VAS). |
| Change From Baseline to Week 16 in the Disease Activity Score-28 (C-Reactive Protein) (DAS28 (CRP)) Response | From Baseline to Week 16 | DAS28\[CRP\] is a composite index and is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) C-reactive protein (CRP in mg/l), 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) + 0.36 x lognat (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. A DAS(28) score of higher than 5.1 is indicative of high disease activity whereas a DAS score below 3.2 indicates low disease activity. A patient is considered to be in remission if they have a DAS28 lower than 2.6. A negative value in DAS28\[CRP\] change from Baseline indicates an improvement from Baseline. |
| Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16 | From Baseline to Week 16 | DAS28\[CRP\] is a composite index and is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) C-reactive protein (CRP in mg/l), 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) + 0.36 x lognat (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. A DAS(28) score of higher than 5.1 is indicative of high disease activity whereas a DAS score below 3.2 indicates low disease activity. A patient is considered to be in remission if they have a DAS28 lower than 2.6. |
| Change From Baseline to Week 16 in Bone Mineral Density as Measured by Digital XRay (DXR) | From Baseline to Week 16 | Radiographic assessment of bone mineral density in one hand and wrist were conducted by Digital X Ray (DXR) using a standardized imaging methodology. The hand and wrist to be assessed by DXR were the same as for the Magnetic Resonance Images (MRIs). The same hand and wrist were used for all x rays. The evaluation of all DXRs was performed centrally. A positive value in Bone Mineral Density change from Baseline indicates an improvement. |
| Change From Baseline to Week 16 in Tender Joint Count (TJC) | From Baseline to Week 16 | The joint assessment was carried out on 28 joints. Swelling and tenderness were graded on a 2-point scale (answered with Yes/No). No indicated Not tender; Yes indicated a positive tenderness response that was defined as a positive response to questioning (tender), spontaneous response elicited (tender and winced) or withdrawal by subject on examination (tender, winced, and withdrew). If there were missing observations in the TJC, then the remaining observations were assessed and weighted by dividing by the number of non-missing joint counts and multiplying by 28. TJC ranges from 0 to 28 with 0 indicating no tender joints and 28 indicating tenderness in all joints. A negative value in TJC change from Baseline indicates an improvement. |
| Change From Baseline to Week 16 in Swollen Joint Count (SJC) | From Baseline to Week 16 | The joint assessment was carried out on 28 joints. Swelling and tenderness were graded on a 2-point scale (answered with Yes/No). No indicated None swelling response and Yes indicated that there was a detectable synovial thickening with or without loss of bony contours, or bulging synovial proliferation with or without cystic characteristics. If there were missing observations in the SJC, then the remaining observations were assessed and weighted by dividing by the number of non-missing joint counts and multiplying by 28. SJC ranges from 0 to 28 with 0 indicating no swollen joints and 28 indicating swelling in all joints. A negative value in SJC change from Baseline indicates an improvement. |
| Change From Baseline to Week 16 in Health Assessment Questionnaire - Disability Index (HAQ-DI) | From Baseline to Week 16 | The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a subject reported questionnaire that provides an assessment of the impact of the disease and its treatment on physical function. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question the level of difficulty is scored from 0 to 3 where 0 = no difficulty, 1 = some difficulty, 2 = much difficulty and 3 = unable to do. A total score is computed from the item scores using the scoring rules provided by the author (Fries, 1980). The total score ranges from 0 to 3 with lower scores meaning lower disability. A negative value in HAQ-DI change from Baseline indicates an improvement. |
| Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Initiation Rate of Enhancement (IRE) | From Baseline to Week 16 | Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest. Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume . ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16. The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in IRE change from Baseline score indicates an improvement. |
| Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With European League Against Rheumatism (EULAR) Response at Week 16 | From Baseline to Week 16 | EULAR (European League Against Rheumatism) response: EULAR response is based upon current Disease Activity Score 28 (DAS28) level and corresponding change from Baseline in DAS28. Good EULAR response is defined as: DAS28 C-Reactive Protein (CRP) ≤ 3.2 and decrease from Baseline by \> 1.2; moderate response is defined as achievement of one of the following: * DAS28(CRP) ≤ 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2 * DAS28(CRP) \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6 * DAS28(CRP) \> 5.1 and decrease from Baseline \> 1.2 A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with better EULAR responses. |
| Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 20 % Criteria (ACR20) at Week 16 | From Baseline to Week 16 | Subjects who meet the ACR20 criteria are those subjects with at least 20 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS). A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR20 response at Week 16. |
| Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 50 % Criteria (ACR50) at Week 16 | From Baseline to Week 16 | Subjects who meet the ACR50 criteria are those 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 (PhGA-VAS). A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR50 response at Week 16. |
| Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 70 % Criteria (ACR70) at Week 16 | From Baseline to Week 16 | Subjects who meet the ACR70 criteria are those 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 (PhGA-VAS). A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR70 response at Week 16. |
| Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Disease Activity Score-28 (DAS28 (CRP)) Response at Week 16 | From Baseline to Week 16 | The DAS28(CRP) was calculated using the tender joint count (TJC) and swollen joint count (SJC), C-Reactive Protein (CRP in mg/L) and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm). A positive correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with reductions in DAS28(CRP) at Week 16. |
| Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Changes in Hand Bone Mineral Density as Measured by Digital XRay (DXR) at Week 16 | From Baseline to Week 16 | Radiographic assessment of bone mineral density in one hand and wrist were conducted by Digital X Ray (DXR) using a standardized imaging methodology. The hand and wrist to be assessed by DXR were the same as for the Magnetic Resonance Images (MRIs). The same hand and wrist were used for all x rays. The evaluation of all DXRs was performed centrally. A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with increases in bone mineral density at Week 16. |
| Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 1 Placebo (PBO) Versus Certolizumab Pegol (CZP) | From Baseline to Week 1 | Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions (the distal radioulnar; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. A negative value in synovitis change from Baseline score indicates an improvement. |
| Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 2 Placebo (PBO) Versus Certolizumab Pegol (CZP) | From Baseline to Week 2 | Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions (the distal radioulnar; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. A negative value in synovitis change from Baseline score indicates an improvement. |
| C-Reactive Protein (CRP) Ratio to Baseline at Week 16 | From Baseline to Week 16 | The C-Reactive Protein (CRP) is considered a marker of inflammation in subjects with Rheumatoid Arthritis. A ratio to Baseline \< 1 indicates an improvement. |
| Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Maximal Enhancement (ME) | From Baseline to Week 16 | Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest. Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume . ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16. The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in ME change from Baseline score indicates an improvement. |
| Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Number of Voxels (Nvox) With Plateau and Washout Pattern | From Baseline to Week 16 | Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest. Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume . ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16. The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in Nvox change from Baseline score indicates an improvement. |
| Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 | From Baseline to Week 16 | EULAR (European League Against Rheumatism) response: EULAR response is based upon current Disease Activity Score 28 (DAS28) level and corresponding change from Baseline in DAS28. Good EULAR response is defined as: DAS28 C-Reactive Protein (CRP) ≤ 3.2 and decrease from Baseline by \> 1.2; moderate response is defined as achievement of one of the following: * DAS28(CRP) ≤ 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2 * DAS28(CRP) \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6 * DAS28(CRP) \> 5.1 and decrease from Baseline \> 1.2 |
| Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16 | From Baseline to Week 16 | Subjects who meet the ACR20 criteria are those subjects with at least 20 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS). |
Countries
Denmark, Netherlands, Poland, Sweden
Participant flow
Recruitment details
The Participant Flow refers to the Randomized Set (RS) population which consists of all subjects randomized into the study.
Pre-assignment details
The study population consists of subjects with a diagnosis of adult-onset Rheumatoid Arthritis of at least 3 months duration but not longer than 15 years. In addition, subjects must be on Disease Modifying Anti-Rheumatic Drugs (DMARD) therapy for at least 12 weeks with a stable dose / route of administration for at least 8 weeks prior to Baseline.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Followed by Certolizumab Pegol (CZP) Placebo, saline solution for subcutaneous injection at Week 0 followed by Certolizumab Pegol (CZP) 400 mg at Weeks 2, 4, and 6, then Certolizumab Pegol (CZP) 200 mg 2-weekly from Week 8 to Week 40 | 13 |
| Certolizumab Pegol (CZP) Certolizumab Pegol (CZP) 400 mg for subcutaneous injection at Weeks 0, 2 and 4 followed by 200 mg 2-weekly from Week 6 to Week 40 | 27 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Certolizumab Pegol (CZP) | Placebo Followed by Certolizumab Pegol (CZP) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 6 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 21 Participants | 11 Participants |
| Age, Continuous | 50.4 years STANDARD_DEVIATION 13.1 | 51.3 years STANDARD_DEVIATION 12.6 | 48.3 years STANDARD_DEVIATION 14.4 |
| Region of Enrollment Denmark | 17 participants | 11 participants | 6 participants |
| Region of Enrollment Netherlands | 4 participants | 3 participants | 1 participants |
| Region of Enrollment Poland | 9 participants | 7 participants | 2 participants |
| Region of Enrollment Sweden | 10 participants | 6 participants | 4 participants |
| Sex: Female, Male Female | 32 Participants | 22 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 40 |
| serious Total, serious adverse events | 4 / 40 |
Outcome results
Primary
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 16 Compared to Baseline for Certolizumab Pegol Arm
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 16 Compared to Baseline for Certolizumab Pegol Arm | -1.0 scores on a scale | Standard Deviation 2.3 |
Comparison: A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p \<0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.p-value: 0.04995% CI: [-3, 0]Permutation test with general scores
Primary
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 1 Compared to Baseline for Certolizumab Pegol Arm
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 1
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 1 Compared to Baseline for Certolizumab Pegol Arm | -0.6 scores on a scale | Standard Deviation 1.8 |
Primary
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 2 Compared to Baseline for Certolizumab Pegol Arm
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 2
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 2 Compared to Baseline for Certolizumab Pegol Arm | -0.4 scores on a scale | Standard Deviation 1.6 |
Primary
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 4 Compared to Baseline for Certolizumab Pegol Arm
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 4
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 4 Compared to Baseline for Certolizumab Pegol Arm | -0.4 scores on a scale | Standard Deviation 1.6 |
Primary
Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 8 Compared to Baseline for Certolizumab Pegol Arm
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 21. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 8
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score at Week 8 Compared to Baseline for Certolizumab Pegol Arm | -0.7 scores on a scale | Standard Deviation 2.6 |
Comparison: A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p \< 0.05). Hypothesis testing was stopped if and when a non-significant result was obtained. Testing was stopped in the next step.p-value: 0.20695% CI: [-3, 1]Permutation test with general scores
Secondary
Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 1 Placebo (PBO) Versus Certolizumab Pegol (CZP)
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions (the distal radioulnar; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 1
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 1 Placebo (PBO) Versus Certolizumab Pegol (CZP) | 0.1 scores on a scale | Standard Deviation 1 |
| Placebo Followed by Certolizumab Pegol (CZP) | Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 1 Placebo (PBO) Versus Certolizumab Pegol (CZP) | -0.6 scores on a scale | Standard Deviation 1.8 |
p-value: 0.25495% CI: [-1, 0]Wilcoxon Rank-Sum Test
Secondary
Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 2 Placebo (PBO) Versus Certolizumab Pegol (CZP)
Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS): Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions (the distal radioulnar; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each of the second through fifth metacarpophalangeal (MCP) joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. A negative value in synovitis change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 2
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 2 Placebo (PBO) Versus Certolizumab Pegol (CZP) | 0.2 scores on a scale | Standard Deviation 1.4 |
| Placebo Followed by Certolizumab Pegol (CZP) | Change From Baseline for the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Synovitis Score at Week 2 Placebo (PBO) Versus Certolizumab Pegol (CZP) | -0.4 scores on a scale | Standard Deviation 1.6 |
p-value: 0.47295% CI: [-2, 1]Wilcoxon Rank-Sum Test
Secondary
Change From Baseline to Week 16 in Bone Mineral Density as Measured by Digital XRay (DXR)
Radiographic assessment of bone mineral density in one hand and wrist were conducted by Digital X Ray (DXR) using a standardized imaging methodology. The hand and wrist to be assessed by DXR were the same as for the Magnetic Resonance Images (MRIs). The same hand and wrist were used for all x rays. The evaluation of all DXRs was performed centrally. A positive value in Bone Mineral Density change from Baseline indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Bone Mineral Density as Measured by Digital XRay (DXR) | -0.00606 g/cm^2 | Standard Deviation 0.01185 |
| Placebo Followed by Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Bone Mineral Density as Measured by Digital XRay (DXR) | -0.00630 g/cm^2 | Standard Deviation 0.01032 |
Secondary
Change From Baseline to Week 16 in Health Assessment Questionnaire - Disability Index (HAQ-DI)
The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a subject reported questionnaire that provides an assessment of the impact of the disease and its treatment on physical function. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities, and each domain (activity) consists of 2 or 3 items. For each question the level of difficulty is scored from 0 to 3 where 0 = no difficulty, 1 = some difficulty, 2 = much difficulty and 3 = unable to do. A total score is computed from the item scores using the scoring rules provided by the author (Fries, 1980). The total score ranges from 0 to 3 with lower scores meaning lower disability. A negative value in HAQ-DI change from Baseline indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.54 scores on a scale | Standard Deviation 0.49 |
| Placebo Followed by Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Health Assessment Questionnaire - Disability Index (HAQ-DI) | -0.79 scores on a scale | Standard Deviation 0.49 |
Secondary
Change From Baseline to Week 16 in Swollen Joint Count (SJC)
The joint assessment was carried out on 28 joints. Swelling and tenderness were graded on a 2-point scale (answered with Yes/No). No indicated None swelling response and Yes indicated that there was a detectable synovial thickening with or without loss of bony contours, or bulging synovial proliferation with or without cystic characteristics. If there were missing observations in the SJC, then the remaining observations were assessed and weighted by dividing by the number of non-missing joint counts and multiplying by 28. SJC ranges from 0 to 28 with 0 indicating no swollen joints and 28 indicating swelling in all joints. A negative value in SJC change from Baseline indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Swollen Joint Count (SJC) | -7.06 units on a scale | Standard Deviation 4.67 |
| Placebo Followed by Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Swollen Joint Count (SJC) | -7.92 units on a scale | Standard Deviation 5.81 |
Secondary
Change From Baseline to Week 16 in Tender Joint Count (TJC)
The joint assessment was carried out on 28 joints. Swelling and tenderness were graded on a 2-point scale (answered with Yes/No). No indicated Not tender; Yes indicated a positive tenderness response that was defined as a positive response to questioning (tender), spontaneous response elicited (tender and winced) or withdrawal by subject on examination (tender, winced, and withdrew). If there were missing observations in the TJC, then the remaining observations were assessed and weighted by dividing by the number of non-missing joint counts and multiplying by 28. TJC ranges from 0 to 28 with 0 indicating no tender joints and 28 indicating tenderness in all joints. A negative value in TJC change from Baseline indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Tender Joint Count (TJC) | -9.28 units on a scale | Standard Deviation 5.85 |
| Placebo Followed by Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in Tender Joint Count (TJC) | -9.92 units on a scale | Standard Deviation 8.55 |
Secondary
Change From Baseline to Week 16 in the Disease Activity Score-28 (C-Reactive Protein) (DAS28 (CRP)) Response
DAS28\[CRP\] is a composite index and is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) C-reactive protein (CRP in mg/l), 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) + 0.36 x lognat (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. A DAS(28) score of higher than 5.1 is indicative of high disease activity whereas a DAS score below 3.2 indicates low disease activity. A patient is considered to be in remission if they have a DAS28 lower than 2.6. A negative value in DAS28\[CRP\] change from Baseline indicates an improvement from Baseline.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in the Disease Activity Score-28 (C-Reactive Protein) (DAS28 (CRP)) Response | -2.27 units on a scale | Standard Deviation 0.86 |
| Placebo Followed by Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in the Disease Activity Score-28 (C-Reactive Protein) (DAS28 (CRP)) Response | -2.50 units on a scale | Standard Deviation 1.23 |
Secondary
Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Initiation Rate of Enhancement (IRE)
Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest. Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume . ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16. The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in IRE change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Initiation Rate of Enhancement (IRE) | -0.0044 percent per second | Standard Deviation 0.014 |
Comparison: A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p \<0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.p-value: 0.16495% CI: [-0.012, 0.0025]Permutation test with general scores
Secondary
Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Maximal Enhancement (ME)
Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest. Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume . ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16. The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in ME change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Maximal Enhancement (ME) | -0.0172 percent change over pre-contrast | Standard Deviation 0.4459 |
Comparison: A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p \<0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.p-value: 0.86595% CI: [-0.201, 0.138]Permutation test with general scores
Secondary
Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Number of Voxels (Nvox) With Plateau and Washout Pattern
Contrast enhancement can be quantified in terms of the dynamic MRI parameters initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern. These parameters are extracted by examining individual signal intensity versus time curves derived from defined regions of interest. Nvox indicates the number of voxels showing enhancement patterns. It is representative of the size or volume of enhancement and representative of underlying inflammation. The higher the value, the higher the volume . ME and IRE values quantify the intensity of signal within the enhancing voxels. The absolute values and changes from Baseline in the MRI parameters of IRE, ME, and Nvox of the selected hand and wrist were estimated at Weeks 1, 2, 4, 8, and 16. The values presented are for Proximal Interphalangeal (PIP) and Metacarpophalangeal (MCP) joints combined. A negative value in Nvox change from Baseline score indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (last observation carried forward) which consists of all randomized subjects that received at least one dose of study medication. As pre-specified in the protocol, this analysis is restricted to the Certolizumab Pegol (CZP) arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline to Week 16 in the Dynamic Magnetic Resonance Image (MRI) Parameter, Number of Voxels (Nvox) With Plateau and Washout Pattern | -813.3 voxels | Standard Deviation 1457.3 |
Comparison: A fixed-sequence stepwise hypothesis testing procedure was followed using a pre-specified set of ordered hypotheses. Hypotheses were ordered and tested in that order, beginning with change from Baseline at Week 16, and continuing to earlier time points (Week 8, 4, 2, 1 in that order) only if the previous null hypothesis of zero difference was rejected (p \<0.05). Hypothesis testing was stopped if and when a non-significant result was obtained.p-value: 0.01595% CI: [-1542.5, -47]Permutation test with general scores
Secondary
Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 20 % Criteria (ACR20) at Week 16
Subjects who meet the ACR20 criteria are those subjects with at least 20 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS). A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR20 response at Week 16.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 20 % Criteria (ACR20) at Week 16 | -0.11 Spearman rank correlation coefficient |
p-value: 0.625Spearman rank correlation
Secondary
Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 50 % Criteria (ACR50) at Week 16
Subjects who meet the ACR50 criteria are those 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 (PhGA-VAS). A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR50 response at Week 16.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 50 % Criteria (ACR50) at Week 16 | -0.34 Spearman rank correlation coefficient |
p-value: 0.128Spearman rank correlation
Secondary
Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 70 % Criteria (ACR70) at Week 16
Subjects who meet the ACR70 criteria are those 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 (PhGA-VAS). A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with an ACR70 response at Week 16.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With American College of Rheumatology 70 % Criteria (ACR70) at Week 16 | -0.08 Spearman rank correlation coefficient |
p-value: 0.732Spearman rank correlation
Secondary
Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Changes in Hand Bone Mineral Density as Measured by Digital XRay (DXR) at Week 16
Radiographic assessment of bone mineral density in one hand and wrist were conducted by Digital X Ray (DXR) using a standardized imaging methodology. The hand and wrist to be assessed by DXR were the same as for the Magnetic Resonance Images (MRIs). The same hand and wrist were used for all x rays. The evaluation of all DXRs was performed centrally. A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with increases in bone mineral density at Week 16.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Changes in Hand Bone Mineral Density as Measured by Digital XRay (DXR) at Week 16 | 0.32 Spearman rank correlation coefficient |
p-value: 0.208Spearman rank correlation
Secondary
Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Disease Activity Score-28 (DAS28 (CRP)) Response at Week 16
The DAS28(CRP) was calculated using the tender joint count (TJC) and swollen joint count (SJC), C-Reactive Protein (CRP in mg/L) and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm). A positive correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with reductions in DAS28(CRP) at Week 16.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With Disease Activity Score-28 (DAS28 (CRP)) Response at Week 16 | 0.19 Spearman rank correlation coefficient |
p-value: 0.411Spearman rank correlation
Secondary
Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With European League Against Rheumatism (EULAR) Response at Week 16
EULAR (European League Against Rheumatism) response: EULAR response is based upon current Disease Activity Score 28 (DAS28) level and corresponding change from Baseline in DAS28. Good EULAR response is defined as: DAS28 C-Reactive Protein (CRP) ≤ 3.2 and decrease from Baseline by \> 1.2; moderate response is defined as achievement of one of the following: * DAS28(CRP) ≤ 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2 * DAS28(CRP) \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6 * DAS28(CRP) \> 5.1 and decrease from Baseline \> 1.2 A negative correlation coefficient indicates that reductions in synovitis from Baseline to Week 16 are associated with better EULAR responses.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication. Correlations between the change from Baseline in total synovitis score at Week 16 and the clinical efficacy variables are restricted to the Certolizumab Pegol (CZP) arm only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | Correlation of Change in Synovitis From Baseline as Measured by Magnetic Resonance Image (MRI) With European League Against Rheumatism (EULAR) Response at Week 16 | -0.20 Spearman rank correlation coefficient |
p-value: 0.394Spearman rank correlation
Secondary
C-Reactive Protein (CRP) Ratio to Baseline at Week 16
The C-Reactive Protein (CRP) is considered a marker of inflammation in subjects with Rheumatoid Arthritis. A ratio to Baseline \< 1 indicates an improvement.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | C-Reactive Protein (CRP) Ratio to Baseline at Week 16 | 0.491 ratio | Geometric Coefficient of Variation 175.1 |
| Placebo Followed by Certolizumab Pegol (CZP) | C-Reactive Protein (CRP) Ratio to Baseline at Week 16 | 0.219 ratio | Geometric Coefficient of Variation 147.9 |
Secondary
Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16
EULAR (European League Against Rheumatism) response: EULAR response is based upon current Disease Activity Score 28 (DAS28) level and corresponding change from Baseline in DAS28. Good EULAR response is defined as: DAS28 C-Reactive Protein (CRP) ≤ 3.2 and decrease from Baseline by \> 1.2; moderate response is defined as achievement of one of the following: * DAS28(CRP) ≤ 3.2 and decrease from Baseline \> 0.6 and ≤ 1.2 * DAS28(CRP) \> 3.2 and ≤ 5.1 and decrease from Baseline \> 0.6 * DAS28(CRP) \> 5.1 and decrease from Baseline \> 1.2
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 | No Response | 4.8 percentage of subjects |
| Certolizumab Pegol (CZP) | Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 | Good Response | 71.4 percentage of subjects |
| Certolizumab Pegol (CZP) | Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 | Moderate Response | 23.8 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 | Moderate Response | 25.0 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 | No Response | 8.3 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Achieving a Good European League Against Rheumatism (EULAR) Response at Week 16 | Good Response | 66.7 percentage of subjects |
Secondary
Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16
DAS28\[CRP\] is a composite index and is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) C-reactive protein (CRP in mg/l), 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) + 0.36 x lognat (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. A DAS(28) score of higher than 5.1 is indicative of high disease activity whereas a DAS score below 3.2 indicates low disease activity. A patient is considered to be in remission if they have a DAS28 lower than 2.6.
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication, and had a valid Baseline efficacy assessment and at least one valid post-Baseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16 | Remission | 57.1 percentage of subjects |
| Certolizumab Pegol (CZP) | Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16 | No Remission | 42.9 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16 | Remission | 58.3 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Achieving Disease Activity Score 28 (DAS28 (CRP)) Remission Status (DAS28 (CRP) < 2.6) at Week 16 | No Remission | 41.7 percentage of subjects |
Secondary
Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16
Subjects who meet the ACR20 criteria are those subjects with at least 20 % improvement from Baseline for Tender Joint Count (TJC), Swollen Joint Count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-Reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS).
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16 | Response | 86.4 percentage of subjects |
| Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16 | No Response | 13.6 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16 | Response | 75.0 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 20 % Criteria (ACR20) at Week 16 | No Response | 25.0 percentage of subjects |
Secondary
Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16
Subjects who meet the ACR50 criteria are those 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 (PhGA-VAS).
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16 | Response | 68.2 percentage of subjects |
| Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16 | No Response | 31.8 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16 | Response | 58.3 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 50 % Criteria (ACR50) at Week 16 | No Response | 41.7 percentage of subjects |
Secondary
Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16
Subjects who meet the ACR70 criteria are those 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 (PhGA-VAS).
Time frame: From Baseline to Week 16
Population: The Analysis Population refers to the Full Analysis Set (FAS) (observed case) which consists of all randomized subjects that received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16 | Response | 45.5 percentage of subjects |
| Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16 | No Response | 54.5 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16 | Response | 58.3 percentage of subjects |
| Placebo Followed by Certolizumab Pegol (CZP) | Percentage of Subjects Meeting the American College of Rheumatology 70 % Criteria (ACR70) at Week 16 | No Response | 41.7 percentage of subjects |