Rheumatoid Arthritis
Conditions
Brief summary
The purpose of the study is to assess early signs of response to abatacept+methotrexate in metacarpophalangeal joints in both hands using power Doppler ultrasonography in patients with active rheumatoid arthritis.
Interventions
DRUGAbatacept
Abatacept, 10 mg/kg, solution given intravenously on Days 1, 15, 29,57, 85, 113, 141, and 169
DRUGMethotrexate
Methotrexate administered in a dose of 15 mg/week or higher for at least 3 months and at a stable dose for at least 28 days prior to baseline
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion riteria: * Disease activity defined by a disease activity score 28-C-reactive protein \>3.2, or meeting the following criteria: a tender joint count ≥6; a swollen joint count ≥6; C-reactive protein measurement greater than the upper limit of normal * Diagnosis of rheumatoid arthritis for longer than 6 months from time of initial diagnosis * Total synovitis power Doppler ultrasonography (PDUS) score \>1 for at least 2 metacarpophalangeal (MCP) joints (MCP2-5) and a total synovitis PDUS score ≥1 for at least 1 other MCP joint (MCP2-5) * Concomitant treatment with methotrexate at a dose ≥15 mg for at least 3 months before Day 1 and a stable dose for the last 28 days before Day 1 * No treatment with any background nonbiologic disease-modifying antirheumatic drug (DMARD) other than methotrexate for at least 28 days before treatment (Day 1) * Stable dose of corticosteroids equivalent of 10 mg prednisone /day during the 28 days prior to Day 1 * Naive to treatment with biologic DMARDs Key
Exclusion criteria
* Women of childbearing potential who are unwilling or unable to use birth control * Women who are pregnant or breastfeeding * Meeting all diagnostic criteria for any other rheumatic disease * Previous MCP arthroplasty, with such a procedure scheduled, or anticipating the need for such a procedure during the study. Participants who had undergone or were scheduled to undergo joint arthroplasties other than of the MCP joints were permitted to enroll in the study provided all other eligibility criteria were met. * Active vasculitis of a major organ system with the exception of rheumatoid nodule * Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not related to rheumatoid arthritis * History of cancer in the last 5 years, other than nonmelanoma skin cell cancer cured by local resection or carcinoma in situ. Existing nonmelanoma skin cell cancers should have been removed, the lesion site healed, and residual cancer ruled out prior to administration of study medication * Clinically significant abuse of alcohol or drugs * Evidence of active or latent bacterial or viral infections at the time of potential enrollment * Herpes zoster or cytomegalovirus infection that resolved less than 2 months before the informed consent document was signed * For participants at risk for tuberculosis (TB): * A history of active (TB) within the last 3 years, even if treated * Latent TB that was not successfully treated ≥4 weeks * Current clinical, radiographic, or laboratory evidence of active TB. * Participants who have received live vaccines within 3 months of the anticipated first dose of study medication * Participants with positive test results for hepatitis B surface antigen or hepatitis C antibody, with hepatitis C virus detected with polymerase chain reaction or recombinant immunoblot assay. * Participants with hemoglobin level \<8.5 g/dL or white blood cell count\< 3000/mm\^3 or platelet count \<100,000/mm\^3 or serum creatinin level \>2\*the upper limit of normal (ULN) or serum alanine transaminase level or aspartate aminotransferase level \>2\*ULN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169 | LOCF=last observation carried forward. PDUS assessed the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. Total PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and Grade 2 Doppler signal; Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤Grade 3 Doppler signal or minimal or moderate synovial hypertrophy and Grade 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8\*1, 8\*3) for 2 hands. Higher grade/score=more severe disease. Change=score Day x - baseline score. |
| Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed | Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169 | MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography. Time point at which early signs of Global PDUS improvement were observed=earliest time point for which 0 was not included in the 95% confidence interval for the mean changes from baseline in Global PDUS (MCP 2-5) score at that and all later time points. Total PDUS scores are independent of the presence and grade of joint effusion: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy \[SH\], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH, with ≤Gr 2 Doppler signal or minimal SH and grade 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8\*1, 8\*3) for the 2 hands. Higher Gr/score=more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Days 7, 15, 29, and 169 | PDUS=power Doppler ultrasonography; MCP=metacarpophalangeal; LOCF=last observation carried forward. PDUS was used to assess the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and grade 2 Doppler signal); Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤ Grade 3 Doppler signal or minimal or 1-3, for a total possible score ranging from 8 to 24 (8\*1, 8\*3) for the 2 hands. Higher grade/score=more severe disease. Change=score Day X-baseline score. |
| Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP | Days 1 to 169 | MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography; DAS=Disease Activity Score;CRP=C-reactive protein. Receiver Operator Characteristics (ROC) analysis assessed predicatability. ROC curve analyses performed; area under the curve of ≥0.7 was considered acceptable for prediction. Clinical response defined as: Clinically Meaningful Improvement=drop from baseline of ≥1.2 in DAS28-CRP; Remission=DAS28-CRP score \<2.6; Low Disease Activity=≤3.2. PDUS scores: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy \[SH\], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH with ≤Gr 2 Doppler signal or minimal SH and Gr 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint rated 1-3, for a total possible score ranging from 8-24 (8\*1, 8\*3)for the 2 hands. Higher gr/score=more severe disease. |
| Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | Days 1 to 169 to 56 days following last infusion | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. |
| Number of Participants With Adverse Events (AEs) of Interest | Days 1 to 169 to 56 days following last infusion | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Infusion reaction: acute=1 hour or less after start of dosing; periinfusional=24 hours or less after start of dosing. |
Countries
Denmark, France, Germany, Hungary, Italy, Norway, Spain, United Kingdom
Participant flow
Pre-assignment details
A total of 164 participants were screened; 104 were enrolled in the study and received open-label treatment with abatacept.
Participants by arm
| Arm | Count |
|---|---|
| Abatacept, 10 mg/kg All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening. | 104 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Missed visit due to family reasons | 1 |
| Overall Study | No longer met study criteria | 2 |
Baseline characteristics
| Characteristic | Abatacept, 10 mg/kg |
|---|---|
| Age Continuous | 56.4 Years STANDARD_DEVIATION 14.1 |
| DAS 28-CRP score | 5.2888 Units on a scale STANDARD_DEVIATION 1.105 |
| Duration of rheumatoid arthritis | 7.3 Years STANDARD_DEVIATION 9.1 |
| Global PDUS (MCP 2-5) score (n=96) | 12.6 Units on a scale STANDARD_DEVIATION 4.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 101 Participants |
| Sex: Female, Male Female | 87 Participants |
| Sex: Female, Male Male | 17 Participants |
| Swollen joint count | 13.0 Joints STANDARD_DEVIATION 7.6 |
| Tender joint count | 19.5 Joints STANDARD_DEVIATION 12.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 104 |
| serious Total, serious adverse events | 6 / 104 |
Outcome results
Primary
Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed
MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography. Time point at which early signs of Global PDUS improvement were observed=earliest time point for which 0 was not included in the 95% confidence interval for the mean changes from baseline in Global PDUS (MCP 2-5) score at that and all later time points. Total PDUS scores are independent of the presence and grade of joint effusion: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy \[SH\], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH, with ≤Gr 2 Doppler signal or minimal SH and grade 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8\*1, 8\*3) for the 2 hands. Higher Gr/score=more severe disease.
Time frame: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169
Population: All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept, 10 mg/kg | Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed | 7 Day |
Primary
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis)
LOCF=last observation carried forward. PDUS assessed the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. Total PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and Grade 2 Doppler signal; Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤Grade 3 Doppler signal or minimal or moderate synovial hypertrophy and Grade 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8\*1, 8\*3) for 2 hands. Higher grade/score=more severe disease. Change=score Day x - baseline score.
Time frame: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169
Population: All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 7 (n=86) | -0.7 Units on a scale | 95% Confidence Interval 0.282 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 15 (n=94) | -1.3 Units on a scale | 95% Confidence Interval 0.308 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 29 (n=95) | -2.4 Units on a scale | 95% Confidence Interval 0.383 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 43 (n=95) | -2.9 Units on a scale | 95% Confidence Interval 0.384 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 57 (n=95) | -3.2 Units on a scale | 95% Confidence Interval 0.393 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 85 (n=95) | -3.8 Units on a scale | 95% Confidence Interval 0.454 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 113 (n=95) | -4.5 Units on a scale | 95% Confidence Interval 0.472 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 141 (n=95) | -4.8 Units on a scale | 95% Confidence Interval 0.492 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) | Day 169 (n=95) | -4.8 Units on a scale | 95% Confidence Interval 0.473 |
95% CI: [-1.2, -0.1]
95% CI: [-2, -0.7]
95% CI: [-3.2, -1.7]
95% CI: [-3.7, -2.1]
95% CI: [-4, -2.4]
95% CI: [-4.7, -2.9]
95% CI: [-5.4, -3.5]
95% CI: [-5.8, -3.8]
95% CI: [-5.8, -3.9]
Secondary
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis)
PDUS=power Doppler ultrasonography; MCP=metacarpophalangeal; LOCF=last observation carried forward. PDUS was used to assess the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and grade 2 Doppler signal); Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤ Grade 3 Doppler signal or minimal or 1-3, for a total possible score ranging from 8 to 24 (8\*1, 8\*3) for the 2 hands. Higher grade/score=more severe disease. Change=score Day X-baseline score.
Time frame: Days 7, 15, 29, and 169
Population: All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Synovial hypertrophy (n=86): Day 7 | -0.6 Units on a scale | Standard Error 0.297 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Synovial hypertrophy (n=94): Day 15 | -1.0 Units on a scale | Standard Error 0.306 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Synovial hypertrophy (n=95): Day 29 | -2.1 Units on a scale | Standard Error 0.377 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Synovial hypertrophy (n=95): Day 169 | -4.5 Units on a scale | Standard Error 0.449 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Doppler signal: Day 7 (n=86) | -0.9 Units on a scale | Standard Error 0.305 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Doppler signal: Day 15 (n=94) | -1.9 Units on a scale | Standard Error 0.296 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Doppler signal: Day 29 (n=95) | -2.2 Units on a scale | Standard Error 0.35 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Doppler signal: Day 169 (n=95) | -4.8 Units on a scale | Standard Error 0.457 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Joint effusion: Day 7 (n=86) | 0.1 Units on a scale | Standard Error 0.237 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Joint effusion: Day 15 (n=94) | 0.1 Units on a scale | Standard Error 0.243 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Joint effusion: Day 29 (n=95) | -0.8 Units on a scale | Standard Error 0.294 |
| Abatacept, 10 mg/kg | Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) | Joint effusion: Day 169 (n=95) | -1.9 Units on a scale | Standard Error 0.351 |
Secondary
Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP
MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography; DAS=Disease Activity Score;CRP=C-reactive protein. Receiver Operator Characteristics (ROC) analysis assessed predicatability. ROC curve analyses performed; area under the curve of ≥0.7 was considered acceptable for prediction. Clinical response defined as: Clinically Meaningful Improvement=drop from baseline of ≥1.2 in DAS28-CRP; Remission=DAS28-CRP score \<2.6; Low Disease Activity=≤3.2. PDUS scores: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy \[SH\], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH with ≤Gr 2 Doppler signal or minimal SH and Gr 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint rated 1-3, for a total possible score ranging from 8-24 (8\*1, 8\*3)for the 2 hands. Higher gr/score=more severe disease.
Time frame: Days 1 to 169
Population: All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP | Clinically meaningful improvement | 0 Scores |
| Abatacept, 10 mg/kg | Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP | Remission | 0 Scores |
| Abatacept, 10 mg/kg | Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP | Low disease activity | 0 Scores |
Secondary
Number of Participants With Adverse Events (AEs) of Interest
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Infusion reaction: acute=1 hour or less after start of dosing; periinfusional=24 hours or less after start of dosing.
Time frame: Days 1 to 169 to 56 days following last infusion
Population: All participants who received at least 1 infusion of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Number of Participants With Adverse Events (AEs) of Interest | Infections | 20 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Adverse Events (AEs) of Interest | Malignancy | 1 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Adverse Events (AEs) of Interest | Autoimmune disorders (prespecified) | 2 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Adverse Events (AEs) of Interest | Infusion reactions (prespecified): Acute | 4 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Adverse Events (AEs) of Interest | Infusion reactions (prespecified): Periinfusional | 10 Participants |
Secondary
Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Time frame: Days 1 to 169 to 56 days following last infusion
Population: All participants who received at least 1 infusion of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | AEs | 62 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | Deaths | 0 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | SAEs | 6 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | Treatment-related SAEs | 2 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | Discontinuations due to SAEs | 1 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | Treatment-related AEs | 22 Participants |
| Abatacept, 10 mg/kg | Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs | Discontinuations due to AEs | 6 Participants |