Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, with inadequate response to methotrexate
Brief summary
The purpose of the study is to demonstrate the clinical efficacy of abatacept (body-weight tiered dose approximating 10 mg/kg) compared with placebo on a background of methotrexate after 6 months (Day 169) of treatment in Korean patients with active rheumatoid arthritis and an inadequate clinical response to methotrexate
Interventions
DRUGAbatacept
Intravenous (IV) solution, - weight tiered (500 mg \<60 kg); (750 mg 60-100 kg); (1 gram \> 100 kg), Day 1, Day 15, Day 29; every 28 days thereafter, 6 months
DRUGMethotrexate
Tablets, Oral, ≥ 15 mg, weekly, 6 months
DRUGPlacebo
IV solution, Intravenous, D5W, Day 1, Day 15, Day 29; every 28 days thereafter, 6 months
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Rheumatoid arthritis (RA) for longer than 1 year from the time of the initial diagnosis of RA * Patients must have been taking methotrexate for at least 3 months with at least a weekly dose of 15 mg, and a stable dose for 28 days prior to treatment (Day 1) * Methotrexate weekly dose as low as 10 mg is permitted for patients who cannot tolerate higher doses Key
Exclusion criteria
* Evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20) | At Day 169 | The ACR 20 is based on 20% improvement (compared with baseline values) in tender and swollen joint counts and on 20% improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value. |
| Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | Day 169 to up to 56 days post the last dose (Day 1485) in the LTE period | AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | From Baseline to Days 169 and 1485 | Adjusted mean change from baseline. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of rheumatoid arthritis (\>5.1=high disease activity; \<3.2=low disease activity; \<2.6=remission). CRP or ESR give estimations of DAS28 values on a group level. Change from Baseline=Postbaseline - Baseline value. |
| Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | From Baseline to Day 169 | Adjusted mean change from baseline. The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning. Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24. Higher score indicates greater disability. Change from baseline= postbaseline - baseline value. |
| Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains | From Baseline to Day 169 | Adjusted mean change from baseline. The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life and comprised of 8 domains( including 4 physical and 4 mental subscales) used to derive the physical and mental component summary scores. All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Change from baseline=postbaseline - baseline value. |
| Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Throughout double-blind study period (up to Day 169); table includes data up to 56 days past double-blind period or start of the open-label period, whichever occurred first. | AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. |
| Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half) | At the end of infusion and 2 to 4 hours after the start of infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113 | Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. Tmax = the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination. T-Half = the biological half-life or elimination half life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity. |
| Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax) | At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113 | Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. Maximum Concentration (Cmax)= the maximum plasma concentration of the drug. |
| Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC) | At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113 | Area Under the Plasma Concentration-Time Curve (AUC), a measure of drug absorption, in a dosing interval of 28 days from Day 85 to Day 113. Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. |
| Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT) | Day 29, every 28 days until Day 141 | Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. Clearance is a pharmacokinetic parameter that describes how quickly drugs are eliminated, metabolized or distributed throughout the body. |
| Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS) | At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113 | The volume of distribution of drug at steady state (VSS). Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. |
| Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85 | Minimum concentration (Cmin) of Abatacept 500 mg and 750 mg at given time points |
| Immunogenicity of Abatacept- Number of Participants With Reactivity Toward CTLA4-IG and CTLA4-T at Day 169 | Day 169 | Immunogenicity was determined by measuring adult subject sera for reactivity against the whole Abatacept molecule (CTLA4Ig) and CTLA4-T (CTLA4 without the Ig regions). |
| Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169 | At Day 169 | The ACR defines ACR 50 and ACR70 response as a 50% or 70% improvement (compared with baseline values) in tender and swollen joint counts and 50% or 70% improvement in 3 of the remaining 5 core set measures (patient global assessment of pain, patient global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function) and 1 acute phase reactant value (C-reactive protein). |
| Change From Baseline in Surrogate Marker Rheumatoid Factor (RF) at Day 169 | Baseline, Day 169 | Mean change in RF. A surrogate marker is an indirect measurement of effectiveness. Mean change from Baseline = postbaseline - baseline value. |
| LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples | Days 169, at 6-month intervals on-treatment, and at Days 28, 56, and 85 after the last infusion of study medication in the LTE period | Positive antibody titers were identified by validated enzyme-linked immunosorbent assay results. On-treatment samples were obtained during the LTE period, and posttreatment samples were following the last infusion of study medication. |
| Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Days 15 through 1569 | The ACR 20, ACR50, and ACR70 are based on 20%, 50% and 70% improvement, respectively, (compared with baseline values) in tender and swollen joint counts and on 20%, 50% and 70%, respectively, improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value. |
| Percentage of Participants With Physical Function Response as Assessed Using the Health Assessment Questionnaire Disability Index (HAQ-DI) | At Day 1485 | Improvement is measured by an improved response of at least 0.3 units from baseline on the HAQ-DI score. The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning. Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24. Higher score indicates greater disability. Change from baseline= postbaseline - baseline value. |
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Day 1485 | The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning. Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24. Higher score indicates greater disability. Change from baseline= postbaseline - baseline value. |
| Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries | At Day 1485 | The SF-36 is a 36-item questionnaire used to measure Quality of Life over 8 physically and emotionally based areas: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health. Answers to each question correspond to a precoded numeric value. An aggregate percentage score is reached for each of the 8 sections and is based on answers to questions. The mean average is worked out for each section. Scores range from 0% (lowest level of functioning) to 100% (highest level of functioning, with higher score indicated increasing levels of functioning. |
| Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | At Days 169 and 1485 | EULAR defines LDAS as a disease activity score as measured by c-reactive protein (DAS28-CRP) ≤3.2 and remission as DAS28-CRP \<2.6 |
| Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | At Days 169 and 1569 | The SDAI is the sum of 5 parameters: Tender joint (TJC) and swollen joint(SJC)counts, based on a 28-joint assessment; patient global (PtGA)and physician global assessments (PGA), assessed on 0-10 cm visual analog scale (VAS), on which higher scores=greater affection due to disease activity DA); and C-reactive protein level. SDAI total score=0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11=low DA, \>11 to 26=moderate DA, and \>26=high DA. SJC is assessed at each visit, with no swelling=0, swelling=1. TJC is assessed through identification of joints painful under pressure or to passive motion at each visit, with no tenderness=0, tenderness=1. Higher score=greater affection due to DA. CDAI is sum of 4 parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PGA (assessed on 0-10 cm VAS; higher scores=greater affection due to disease activity). CDAI total score=0-76. CDAI \<=2.8 indicates disease remission, \>2.8 to 10=low DA, \>10 to 22=moderate DA, and \>22=high DA. |
| Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | At Days 169, 337, 729, 1149, and 1485 | LDAS is defined as a Disease Activity Score C-reactive protein (DAS28-CRP) level \<=3.2. Remission is defined as a DAS28-CRP level \<2.6. |
| Change From Baseline in Levels of C-reactive Protein (CRP) | Days 169 to 1569 | — |
| Change From Baseline in Erythrocyte Sedimentation Rate | Days 169 to 1569 | — |
| Change From Baseline in Surrogate Marker Erythrocyte Sedimentation Rate (ESR) at Day 169 | From Baseline to Day 169 | Mean change in surrogate marker mean ESR. A surrogate marker is an indirect measurement of effectiveness. Change from Baseline = postbaseline - baseline value. |
| Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | From Baseline to Day 169 | The ACR defines improvement in core components as 20%, 50%, or 70% improvement in tender and swollen joint counts and 3 of the remaining core components: patient global assessment of disease activity, physician global assessment of disease activity, patient assessment of pain, patient self-assessed disability (Health Assessment Questionnaire Disability Index \[HAQ-DI\]), and levels of 1 acute phase reactant (C-reactive protein levels or erythrocyte sedimentation rate.) The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning; scale=0 (no disability) to 3 (completely disabled); total possible score=24. The higher the score, the greater the disability. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abatacept Dosage: 500 mg to 1 g; participants randomized to the abatacept group received a body-weight tiered dose approximating 10 mg/kg. Study medication was administered intravenously (IV) on Days 1, 15, and 29, and every 28 days thereafter up to and including Day 141 (6 month treatment). | 55 |
| Placebo Study medication was administered intravenously (IV) on Days 1, 15, and 29, and every 28 days thereafter up to and including Day 141 (6 month treatment). | 57 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Long-term Extension Period | Adverse Event | 10 | 0 |
| Long-term Extension Period | Death | 1 | 0 |
| Long-term Extension Period | Lack of Efficacy | 2 | 0 |
| Long-term Extension Period | Poor compliance/noncompliance | 1 | 0 |
| Long-term Extension Period | Pregnancy | 1 | 0 |
| Long-term Extension Period | Withdrawal by Subject | 3 | 0 |
| Short-term Period | Adverse Event | 0 | 1 |
| Short-term Period | Lost to Follow-up | 0 | 1 |
| Short-term Period | Never Treated | 1 | 0 |
| Short-term Period | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Abatacept | Placebo | Total |
|---|---|---|---|
| Age Continuous | 47.2 years STANDARD_DEVIATION 12.2 | 49.9 years STANDARD_DEVIATION 10.6 | 48.6 years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 47 Participants | 49 Participants | 96 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
| weight | 56.5 kilograms STANDARD_DEVIATION 9.5 | 54.2 kilograms STANDARD_DEVIATION 7.5 | 55.3 kilograms STANDARD_DEVIATION 8.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 55 | 26 / 57 |
| serious Total, serious adverse events | 2 / 55 | 3 / 57 |
Outcome results
Primary
Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs
AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time frame: Day 169 to up to 56 days post the last dose (Day 1485) in the LTE period
Population: All participants who completed the short-term period and received at least 1 infusion of abatacept during the LTE period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | Deaths | 1 Participants |
| Abatacept, 10 mg/kg | Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | SAEs | 41 Participants |
| Abatacept, 10 mg/kg | Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | Related SAEs | 10 Participants |
| Abatacept, 10 mg/kg | Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | Discontinuations due to SAEs | 8 Participants |
| Abatacept, 10 mg/kg | Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | AEs | 100 Participants |
| Abatacept, 10 mg/kg | Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | Related AEs | 45 Participants |
| Abatacept, 10 mg/kg | Long-term Extension (LTE) (Open-Label) Period: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuatons Due to SAEs, Adverse Events (AEs), Related AEs, and Discontinuations Due to AEs | Discontinuations due to AEs | 10 Participants |
Primary
Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20)
The ACR 20 is based on 20% improvement (compared with baseline values) in tender and swollen joint counts and on 20% improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value.
Time frame: At Day 169
Population: All randomized participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20) | 65.5 percentage of participants |
| Placebo | Percentage of Participants Meeting the Criteria of the American College of Rheumatology for 20% Improvement (ACR20) | 42.1 percentage of participants |
Secondary
Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC)
Area Under the Plasma Concentration-Time Curve (AUC), a measure of drug absorption, in a dosing interval of 28 days from Day 85 to Day 113. Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg.
Time frame: At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113
Population: Participants with measurement at stated dose level
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept, 10 mg/kg | Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC) | 38940.063 μg.h/mL | Standard Deviation 9731.0561 |
| Placebo | Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC) | 48283.479 μg.h/mL | Standard Deviation 10283.2572 |
| Abatacept 500 mg and 750 mg | Abatacept Pharmacokinetic (PK) Parameters - Area Under the Curve (AUC) | 41881.508 μg.h/mL | Standard Deviation 10743.8152 |
Secondary
Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax)
Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. Maximum Concentration (Cmax)= the maximum plasma concentration of the drug.
Time frame: At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113
Population: Participants with measurement at stated dose level
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept, 10 mg/kg | Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax) | 241.972 μg/mL | Standard Deviation 41.7191 |
| Placebo | Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax) | 312.591 μg/mL | Standard Deviation 63.3026 |
| Abatacept 500 mg and 750 mg | Abatacept Pharmacokinetic (PK) Parameters - Maximum Concentration (Cmax) | 264.204 μg/mL | Standard Deviation 59.0589 |
Secondary
Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half)
Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. Tmax = the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination. T-Half = the biological half-life or elimination half life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity.
Time frame: At the end of infusion and 2 to 4 hours after the start of infusion on Day 85, at anytime between Day 92 and 96, and pre-dose on Day 113
Population: Participants with measurement at stated dose level
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half) | Tmax | 1.385 Hours | Standard Deviation 1.0607 |
| Abatacept, 10 mg/kg | Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half) | T-Half | 183.583 Hours | Standard Deviation 35.2606 |
| Placebo | Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half) | Tmax | 1.193 Hours | Standard Deviation 0.9956 |
| Placebo | Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half) | T-Half | 172.451 Hours | Standard Deviation 28.727 |
| Abatacept 500 mg and 750 mg | Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half) | Tmax | 1.325 Hours | Standard Deviation 1.0351 |
| Abatacept 500 mg and 750 mg | Abatacept Pharmacokinetic (PK) Parameters: Time to Maximum Concentration (Tmax) and Half-Life of Elimination (T-Half) | T-Half | 180.078 Hours | Standard Deviation 33.4795 |
Secondary
Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT)
Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg. Clearance is a pharmacokinetic parameter that describes how quickly drugs are eliminated, metabolized or distributed throughout the body.
Time frame: Day 29, every 28 days until Day 141
Population: Participants with measurement at stated dose level
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept, 10 mg/kg | Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT) | 0.269 mL/h/kg | Standard Deviation 0.073 |
| Placebo | Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT) | 0.240 mL/h/kg | Standard Deviation 0.046 |
| Abatacept 500 mg and 750 mg | Abatacept Pharmacokinetic (PK) Parameters: Total Body Clearance (CLT) | 0.260 mL/h/kg | Standard Deviation 0.0666 |
Secondary
Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS)
The volume of distribution of drug at steady state (VSS). Steady-state PK parameters following administration of body-weight tiered doses approximating 10 mg/kg.
Time frame: At the end of infusion, 2 to 4 hours after the start of infusion on Day 85, anytime between Day 92 and 96, and predose on Day 113
Population: Participants with measurement at stated dose level
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept, 10 mg/kg | Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS) | 0.064 L/kg | Standard Deviation 0.0165 |
| Placebo | Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS) | 0.055 L/kg | Standard Deviation 0.0142 |
| Abatacept 500 mg and 750 mg | Abatacept Pharmacokinetic (PK) Parameters: Volume at Steady State (VSS) | 0.061 L/kg | Standard Deviation 0.0162 |
Secondary
Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR])
Adjusted mean change from baseline. The DAS28 provides a score on a scale from 0 to 10 indicating the current activity of rheumatoid arthritis (\>5.1=high disease activity; \<3.2=low disease activity; \<2.6=remission). CRP or ESR give estimations of DAS28 values on a group level. Change from Baseline=Postbaseline - Baseline value.
Time frame: From Baseline to Days 169 and 1485
Population: All randomized participants who received study drug and who were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 169: DAS28 (CRP) | -2.12 Units on a scale | Standard Error 0.17 |
| Abatacept, 10 mg/kg | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 169: DAS28 (ESR) | -2.22 Units on a scale | Standard Error 0.17 |
| Abatacept, 10 mg/kg | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 1485: DAS28 (CRP) (n=31, 35) | -2.97 Units on a scale | Standard Error 0.23 |
| Abatacept, 10 mg/kg | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 1485: DAS28 (ESR) (NA) | NA Units on a scale | — |
| Placebo | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 1485: DAS28 (ESR) (NA) | NA Units on a scale | — |
| Placebo | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 169: DAS28 (CRP) | -1.21 Units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 1485: DAS28 (CRP) (n=31, 35) | -3.13 Units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in Disease Activity Scores (DAS) Based on C-reactive Protein (DAS 28 [CRP]) Levels or Erythrocyte Sedimentation Rate (DAS 28[ESR]) | Day 169: DAS28 (ESR) | -1.15 Units on a scale | Standard Error 0.16 |
Secondary
Change From Baseline in Erythrocyte Sedimentation Rate
Time frame: Days 169 to 1569
Population: Participants who completed the Short-term Period. n=Number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 169 | -30.60 mm/h | Standard Error 2.93 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 197 (n=53, 49) | -28.43 mm/h | Standard Error 3.27 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 225 | -27.30 mm/h | Standard Error 3.09 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 253 (n=52, 51) | -27.85 mm/h | Standard Error 3.24 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 337 (n=52, 51) | -28.58 mm/h | Standard Error 3.35 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 421 (n=51, 51) | -28.45 mm/h | Standard Error 3.34 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 505 (n=50, 51) | -31.30 mm/h | Standard Error 3.46 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 561 (n=50, 49) | -29.32 mm/h | Standard Error 3.63 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 645 (n=50, 50) | -28.22 mm/h | Standard Error 3.74 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 729 (n=49, 50) | -32.80 mm/h | Standard Error 3.7 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 813 (n=48, 47) | -31.52 mm/h | Standard Error 3.95 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 897 (n=46, 49) | -34.37 mm/h | Standard Error 4.13 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 981 (n=44, 48) | -33.61 mm/h | Standard Error 3.68 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1065 (n=45, 47) | -31.53 mm/h | Standard Error 3.95 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1149 (n=45, 48) | -31.00 mm/h | Standard Error 4.59 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1233 (n=42, 48) | -30.93 mm/h | Standard Error 5.08 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1317 (n=43, 47) | -33.67 mm/h | Standard Error 4.45 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1401 (n=41, 43) | -32.41 mm/h | Standard Error 4.83 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1485 (n=31, 35) | -33.81 mm/h | Standard Error 6.96 |
| Abatacept, 10 mg/kg | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1569 (n=20, 18) | -46.80 mm/h | Standard Error 6.79 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1401 (n=41, 43) | -23.88 mm/h | Standard Error 4.91 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 169 | -7.12 mm/h | Standard Error 3.84 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 813 (n=48, 47) | -22.91 mm/h | Standard Error 4.03 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 197 (n=53, 49) | -15.14 mm/h | Standard Error 3.79 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1233 (n=42, 48) | -22.10 mm/h | Standard Error 4.7 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 225 | -20.27 mm/h | Standard Error 3.51 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 897 (n=46, 49) | -18.22 mm/h | Standard Error 4.65 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 253 (n=52, 51) | -20.78 mm/h | Standard Error 3.97 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1569 (n=20, 18) | -23.33 mm/h | Standard Error 5.85 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 337 (n=52, 51) | -23.86 mm/h | Standard Error 3.78 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 981 (n=44, 48) | -21.54 mm/h | Standard Error 4.53 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 421 (n=51, 51) | -24.94 mm/h | Standard Error 3.86 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1317 (n=43, 47) | -21.89 mm/h | Standard Error 4.48 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 505 (n=50, 51) | -24.69 mm/h | Standard Error 4.07 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1065 (n=45, 47) | -22.09 mm/h | Standard Error 4.37 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 561 (n=50, 49) | -24.90 mm/h | Standard Error 4.24 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1485 (n=31, 35) | -25.69 mm/h | Standard Error 5.7 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 645 (n=50, 50) | -27.38 mm/h | Standard Error 4.1 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 1149 (n=45, 48) | -20.29 mm/h | Standard Error 4.61 |
| Placebo | Change From Baseline in Erythrocyte Sedimentation Rate | Day 729 (n=49, 50) | -23.04 mm/h | Standard Error 3.6 |
Secondary
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning. Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24. Higher score indicates greater disability. Change from baseline= postbaseline - baseline value.
Time frame: Day 1485
Population: All participants who received study drug and who were evaluable
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | -0.76 Units on a scale | Standard Error 0.14 |
| Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | -0.53 Units on a scale | Standard Error 0.11 |
Secondary
Change From Baseline in Levels of C-reactive Protein (CRP)
Time frame: Days 169 to 1569
Population: Participants who completed the Short-term Period. n=Number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 813 (n=48, 49) | -2.24 mg/dL | Standard Error 0.29 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 421 (n=51, 51) | -2.06 mg/dL | Standard Error 0.26 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 897 (n=46, 49) | -2.41 mg/dL | Standard Error 0.3 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 197 (n=53, 49) | -1.87 mg/dL | Standard Error 0.28 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 981 (n=44, 48) | -1.99 mg/dL | Standard Error 0.33 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 505 (n=50, 51) | -2.10 mg/dL | Standard Error 0.28 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1065 (n=45, 48) | -2.06 mg/dL | Standard Error 0.32 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 253 (n=52, 51) | -1.91 mg/dL | Standard Error 0.31 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1149 (n=45, 48) | -2.00 mg/dL | Standard Error 0.34 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 561 (n=50, 50) | -2.23 mg/dL | Standard Error 0.27 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1233 (n=44, 48) | -1.96 mg/dL | Standard Error 0.33 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 169 | -1.85 mg/dL | Standard Error 0.29 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1317 (n=44, 47) | -2.00 mg/dL | Standard Error 0.35 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 645 (n=50, 50) | -2.24 mg/dL | Standard Error 0.28 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1401 (n=41, 43) | -1.93 mg/dL | Standard Error 0.33 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 337 (n=52, 51) | -1.94 mg/dL | Standard Error 0.3 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1485 (n=31, 35) | -1.95 mg/dL | Standard Error 0.47 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 729 (n=49, 50) | -2.29 mg/dL | Standard Error 0.28 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1569 (n=20, 18) | -2.43 mg/dL | Standard Error 0.43 |
| Abatacept, 10 mg/kg | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 225 | -1.73 mg/dL | Standard Error 0.51 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1569 (n=20, 18) | -1.68 mg/dL | Standard Error 0.42 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 197 (n=53, 49) | -1.23 mg/dL | Standard Error 0.36 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 225 | -1.62 mg/dL | Standard Error 0.32 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 253 (n=52, 51) | -1.52 mg/dL | Standard Error 0.32 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 337 (n=52, 51) | -1.67 mg/dL | Standard Error 0.32 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 421 (n=51, 51) | -1.77 mg/dL | Standard Error 0.33 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 505 (n=50, 51) | -1.75 mg/dL | Standard Error 0.33 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 561 (n=50, 50) | -1.68 mg/dL | Standard Error 0.39 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 645 (n=50, 50) | -1.88 mg/dL | Standard Error 0.34 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 729 (n=49, 50) | -1.63 mg/dL | Standard Error 0.37 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 813 (n=48, 49) | -1.81 mg/dL | Standard Error 0.34 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 897 (n=46, 49) | -1.76 mg/dL | Standard Error 0.35 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 981 (n=44, 48) | -1.99 mg/dL | Standard Error 0.36 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1065 (n=45, 48) | -1.47 mg/dL | Standard Error 0.4 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1149 (n=45, 48) | -1.86 mg/dL | Standard Error 0.36 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1233 (n=44, 48) | 1.70 mg/dL | Standard Error 0.37 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1317 (n=44, 47) | -1.81 mg/dL | Standard Error 0.4 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1401 (n=41, 43) | -1.83 mg/dL | Standard Error 0.4 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 1485 (n=31, 35) | -1.86 mg/dL | Standard Error 0.41 |
| Placebo | Change From Baseline in Levels of C-reactive Protein (CRP) | Day 169 | -0.58 mg/dL | Standard Error 0.34 |
Secondary
Change From Baseline in Surrogate Marker Erythrocyte Sedimentation Rate (ESR) at Day 169
Mean change in surrogate marker mean ESR. A surrogate marker is an indirect measurement of effectiveness. Change from Baseline = postbaseline - baseline value.
Time frame: From Baseline to Day 169
Population: All randomized participants who received study drug. Participants with baseline and post-baseline measurements were included, not the participants who had only baseline measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline in Surrogate Marker Erythrocyte Sedimentation Rate (ESR) at Day 169 | -30.0 mm/h | Standard Error 2.86 |
| Placebo | Change From Baseline in Surrogate Marker Erythrocyte Sedimentation Rate (ESR) at Day 169 | -4.44 mm/h | Standard Error 3.87 |
Secondary
Change From Baseline in Surrogate Marker Rheumatoid Factor (RF) at Day 169
Mean change in RF. A surrogate marker is an indirect measurement of effectiveness. Mean change from Baseline = postbaseline - baseline value.
Time frame: Baseline, Day 169
Population: All Randomized and Treated Participants. The summary was based on the last observation carried forward (LOCF) procedure. Participants with baseline and post-baseline measurements were included, not the participants who had only baseline measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline in Surrogate Marker Rheumatoid Factor (RF) at Day 169 | -54.1 IU/mL | Standard Error 20.52 |
| Placebo | Change From Baseline in Surrogate Marker Rheumatoid Factor (RF) at Day 169 | -12.1 IU/mL | Standard Error 14.38 |
Secondary
Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains
Adjusted mean change from baseline. The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life and comprised of 8 domains( including 4 physical and 4 mental subscales) used to derive the physical and mental component summary scores. All subscales were scored using norm-based methods that standardized the scores to a mean of 50 and a standard deviation of 10 in the general population. The scores range from 0 to 100, with a higher score indicating better quality of life. Change from baseline=postbaseline - baseline value.
Time frame: From Baseline to Day 169
Population: All randomized participants who received study drug and were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains | Physical Component Summary | 6.52 Units on a scale | Standard Error 1.05 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains | Mental Component Summary | 8.18 Units on a scale | Standard Error 1.37 |
| Placebo | Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains | Physical Component Summary | 2.16 Units on a scale | Standard Error 1.06 |
| Placebo | Change From Baseline to Day 169 in Analysis of Short-Form 36 (SF-36) Health Survey Questionnaire Domains | Mental Component Summary | 4.36 Units on a scale | Standard Error 1.38 |
Secondary
Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
Adjusted mean change from baseline. The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning. Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24. Higher score indicates greater disability. Change from baseline= postbaseline - baseline value.
Time frame: From Baseline to Day 169
Population: All randomized participants who received study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | HAQ Disability Index | -0.53 Units on a scale | Standard Error 0.07 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Hygiene | -0.37 Units on a scale | Standard Error 0.09 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Arising | -0.58 Units on a scale | Standard Error 0.1 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Reaching | -0.34 Units on a scale | Standard Error 0.11 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Eating | -0.52 Units on a scale | Standard Error 0.09 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Gripping | -0.67 Units on a scale | Standard Error 0.11 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Dressing and Grooming | -0.58 Units on a scale | Standard Error 0.09 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Activities | -0.56 Units on a scale | Standard Error 0.1 |
| Abatacept, 10 mg/kg | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Walking | -0.54 Units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Activities | -0.25 Units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | HAQ Disability Index | -0.24 Units on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Dressing and Grooming | -0.37 Units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Eating | -0.13 Units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Walking | -0.23 Units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Hygiene | -0.21 Units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Reaching | -0.11 Units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Gripping | -0.36 Units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline to Day 169 in Health Assessment Questionnaire Disability Index (HAQ-DI) Score | Arising | -0.36 Units on a scale | Standard Error 0.1 |
Secondary
Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries
The SF-36 is a 36-item questionnaire used to measure Quality of Life over 8 physically and emotionally based areas: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health. Answers to each question correspond to a precoded numeric value. An aggregate percentage score is reached for each of the 8 sections and is based on answers to questions. The mean average is worked out for each section. Scores range from 0% (lowest level of functioning) to 100% (highest level of functioning, with higher score indicated increasing levels of functioning.
Time frame: At Day 1485
Population: All participants who received study drug and who were evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries | Physical component score | 10.34 Units on a scale | Standard Error 1.8 |
| Abatacept, 10 mg/kg | Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries | Mental component score | 7.93 Units on a scale | Standard Error 2.44 |
| Placebo | Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries | Physical component score | 8.48 Units on a scale | Standard Error 1.57 |
| Placebo | Changes From Baseline in Short-Form 36 (SF-36) Physical and Mental Health Summaries | Mental component score | 7.73 Units on a scale | Standard Error 2.34 |
Secondary
Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores
The SDAI is the sum of 5 parameters: Tender joint (TJC) and swollen joint(SJC)counts, based on a 28-joint assessment; patient global (PtGA)and physician global assessments (PGA), assessed on 0-10 cm visual analog scale (VAS), on which higher scores=greater affection due to disease activity DA); and C-reactive protein level. SDAI total score=0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11=low DA, \>11 to 26=moderate DA, and \>26=high DA. SJC is assessed at each visit, with no swelling=0, swelling=1. TJC is assessed through identification of joints painful under pressure or to passive motion at each visit, with no tenderness=0, tenderness=1. Higher score=greater affection due to DA. CDAI is sum of 4 parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PGA (assessed on 0-10 cm VAS; higher scores=greater affection due to disease activity). CDAI total score=0-76. CDAI \<=2.8 indicates disease remission, \>2.8 to 10=low DA, \>10 to 22=moderate DA, and \>22=high DA.
Time frame: At Days 169 and 1569
Population: All participants who received study drug and who were evaluable
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | SDAI score (Day 169) | -22.84 Units on a scale |
| Abatacept, 10 mg/kg | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | SDAI score (Day 1569) (n=20, 18) | -29.74 Units on a scale |
| Abatacept, 10 mg/kg | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | CDAI score (Day 169) | -20.99 Units on a scale |
| Abatacept, 10 mg/kg | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | CDAI score (Day 1569) (n=20, 18) | -27.79 Units on a scale |
| Placebo | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | CDAI score (Day 1569) (n=20, 18) | -27.34 Units on a scale |
| Placebo | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | SDAI score (Day 169) | -14.07 Units on a scale |
| Placebo | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | CDAI score (Day 169) | -13.49 Units on a scale |
| Placebo | Changes From Baseline in the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) Scores | SDAI score (Day 1569) (n=20, 18) | -29.20 Units on a scale |
Secondary
Immunogenicity of Abatacept- Number of Participants With Reactivity Toward CTLA4-IG and CTLA4-T at Day 169
Immunogenicity was determined by measuring adult subject sera for reactivity against the whole Abatacept molecule (CTLA4Ig) and CTLA4-T (CTLA4 without the Ig regions).
Time frame: Day 169
Population: All participants who received study drug (abatacept)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Immunogenicity of Abatacept- Number of Participants With Reactivity Toward CTLA4-IG and CTLA4-T at Day 169 | Reactivity toward CTLA4-T | 0 participants |
| Abatacept, 10 mg/kg | Immunogenicity of Abatacept- Number of Participants With Reactivity Toward CTLA4-IG and CTLA4-T at Day 169 | Reactivity toward CTLA4Ig | 0 participants |
Secondary
LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples
Positive antibody titers were identified by validated enzyme-linked immunosorbent assay results. On-treatment samples were obtained during the LTE period, and posttreatment samples were following the last infusion of study medication.
Time frame: Days 169, at 6-month intervals on-treatment, and at Days 28, 56, and 85 after the last infusion of study medication in the LTE period
Population: All participants who during the LTE period, received at least 1 infusion of abatacept and had at least 1 immunogenicity sample collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples | Overall | 14 Participants |
| Abatacept, 10 mg/kg | LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples | On-treatment | 9 Participants |
| Abatacept, 10 mg/kg | LTE Period: Overall Number of Participants With Positive Results of Immunogenicity Samples | Posttreatment | 11 Participants |
Secondary
Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time
The ACR 20, ACR50, and ACR70 are based on 20%, 50% and 70% improvement, respectively, (compared with baseline values) in tender and swollen joint counts and on 20%, 50% and 70%, respectively, improvement in 3 of the remaining 5 core set measures (participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function) and 1 acute phase reactant value.
Time frame: Days 15 through 1569
Population: All participants who completed the ST period and received at least 1 infusion of abatacept during the LTE period. n=evaluable participants at that timepoint for that measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 15 ACR20 | 13.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1065 ACR70 (n=45, 48) | 42.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 15 ACR50 | 1.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 645 ACR20 (n=50, 50) | 86.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 15 ACR70 | 0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1149 ACR20 (n=45, 48) | 84.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 29 ACR20 | 24.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 813 ACR70 (n=48, 49) | 41.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 29 ACR50 | 1.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1149 ACR50 (n=45, 48) | 55.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 29 ACR70 | 1.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 729 ACR20 (n=49, 50) | 83.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 57 ACR20 (n=52, 52) | 51.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1149 ACR70 (n=45, 48) | 35.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 57 ACR50 (n=52, 52) | 5.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 897 ACR20 (n=46, 49) | 80.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 57 ACR70 (n=52, 52) | 1.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day1233 ACR20 (n=44, 48) | 84.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 85 ACR20 | 58.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 561 ACR70 (n=50, 50) | 38.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 85 ACR50 | 17.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day1233 ACR50 (n=44, 48) | 63.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 85 ACR70 | 5.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 897 ACR50 (n=46, 49) | 56.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 113 ACR20 | 64.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day1233 ACR70 (n=44, 48) | 43.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 113 ACR50 | 30.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 729 ACR50 (n=49, 50) | 63.3 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 113 ACR70 | 3.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1317 ACR20 (n=44, 47) | 90.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 141 ACR20 | 66.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 897 ACR70 (n=46, 49) | 39.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 141 ACR50 | 30.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1317 ACR50 (n=44, 47) | 63.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 141 ACR70 | 15.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 645 ACR50 (n=50, 50) | 54.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 169 ACR20 | 67.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1317 ACR70 (n=44, 47) | 40.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 169 ACR50 | 34.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 981 ACR20 (n=44, 48) | 84.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 169 ACR70 | 15.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1401 ACR20 (n=41, 43) | 90.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 197 ACR20 (n=53, 50) | 75.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 729 ACR70 (n=49, 50) | 34.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 197 ACR50 (n=53, 51) | 45.3 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1401 ACR50 (n=41, 43) | 68.3 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 197 ACR70 (n=53, 51) | 22.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 981 ACR50 (n=44, 48) | 61.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 225 ACR20 | 75.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1401 ACR70 (n=41, 43) | 39.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 225 ACR50 | 49.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 561 ACR50 (n=50, 50) | 64.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 225 ACR70 | 22.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1485 ACR20 (n=31, 35) | 83.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 253 ACR20 (n=52, 51) | 71.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 981 ACR70 (n=43, 48) | 34.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 253 ACR50 (n=52, 51) | 44.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1485 ACR50 (n=31, 35) | 67.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 253 ACR70 (n=52, 51) | 21.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 813 ACR20 (n=48, 49) | 91.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 337 ACR20 (n=52, 51) | 78.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1485 ACR70 (n=31, 35) | 38.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 337 ACR50 (n=52, 51) | 48.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1065 ACR20 (n=45, 48) | 80.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 337 ACR70 (n=52, 51) | 30.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1569 ACR20 (n=20, 18) | 100.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 421 ACR20 (n=51, 51) | 84.3 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 645 ACR70 (n=50, 50) | 38.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 421 ACR50 (n=51, 51) | 49.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1569 ACR50 (n=20, 18) | 80.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 421 ACR70 (n=51, 51) | 29.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1065 ACR50 (n=45, 48) | 64.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 505 ACR20 (n=50, 51) | 88.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1569 ACR70 (n=20, 18) | 30.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 505 ACR50 (n=50, 51) | 62.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 813 ACR50 (n=48, 49) | 58.3 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 505 ACR70 (n=50, 51) | 40.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 561 ACR20 (n=50, 50) | 88.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 505 ACR70 (n=50, 51) | 25.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 561 ACR20 (n=50, 50) | 86.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 561 ACR50 (n=50, 50) | 60.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 561 ACR70 (n=50, 50) | 32.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 645 ACR20 (n=50, 50) | 82.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 645 ACR50 (n=50, 50) | 56.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 645 ACR70 (n=50, 50) | 34.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 729 ACR20 (n=49, 50) | 74.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 729 ACR50 (n=49, 50) | 54.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 729 ACR70 (n=49, 50) | 32.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 813 ACR20 (n=48, 49) | 79.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 813 ACR50 (n=48, 49) | 59.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 813 ACR70 (n=48, 49) | 34.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 897 ACR20 (n=46, 49) | 79.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 897 ACR50 (n=46, 49) | 53.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 897 ACR70 (n=46, 49) | 34.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 981 ACR20 (n=44, 48) | 79.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 981 ACR50 (n=44, 48) | 60.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 981 ACR70 (n=43, 48) | 41.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1065 ACR20 (n=45, 48) | 79.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1065 ACR50 (n=45, 48) | 60.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1065 ACR70 (n=45, 48) | 43.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1149 ACR20 (n=45, 48) | 75.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1149 ACR50 (n=45, 48) | 62.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1149 ACR70 (n=45, 48) | 43.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day1233 ACR20 (n=44, 48) | 79.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day1233 ACR50 (n=44, 48) | 52.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day1233 ACR70 (n=44, 48) | 41.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1317 ACR20 (n=44, 47) | 76.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1317 ACR50 (n=44, 47) | 53.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1317 ACR70 (n=44, 47) | 36.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1401 ACR20 (n=41, 43) | 81.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1401 ACR50 (n=41, 43) | 51.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1401 ACR70 (n=41, 43) | 39.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1485 ACR20 (n=31, 35) | 85.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1485 ACR50 (n=31, 35) | 62.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1485 ACR70 (n=31, 35) | 45.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1569 ACR20 (n=20, 18) | 88.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1569 ACR50 (n=20, 18) | 72.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 1569 ACR70 (n=20, 18) | 44.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 15 ACR20 | 11.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 15 ACR50 | 3.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 15 ACR70 | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 29 ACR20 | 21.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 29 ACR50 | 7.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 29 ACR70 | 3.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 57 ACR20 (n=52, 52) | 23.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 57 ACR50 (n=52, 52) | 7.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 57 ACR70 (n=52, 52) | 5.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 85 ACR20 | 36.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 85 ACR50 | 9.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 85 ACR70 | 7.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 113 ACR20 | 48.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 113 ACR50 | 11.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 113 ACR70 | 7.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 141 ACR20 | 53.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 141 ACR50 | 11.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 141 ACR70 | 7.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 169 ACR20 | 46.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 169 ACR50 | 17.3 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 169 ACR70 | 7.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 197 ACR20 (n=53, 50) | 60.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 197 ACR50 (n=53, 51) | 37.3 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 197 ACR70 (n=53, 51) | 11.8 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 225 ACR20 | 65.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 225 ACR50 | 32.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 225 ACR70 | 13.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 253 ACR20 (n=52, 51) | 64.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 253 ACR50 (n=52, 51) | 35.3 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 253 ACR70 (n=52, 51) | 13.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 337 ACR20 (n=52, 51) | 62.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 337 ACR50 (n=52, 51) | 43.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 337 ACR70 (n=52, 51) | 17.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 421 ACR20 (n=51, 51) | 78.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 421 ACR50 (n=51, 51) | 56.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 421 ACR70 (n=51, 51) | 31.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 505 ACR20 (n=50, 51) | 84.3 Percentage of participants |
| Placebo | Percentage of Participants Achieving ACR20, ACR50, and ACR70 Over Time | Day 505 ACR50 (n=50, 51) | 56.9 Percentage of participants |
Secondary
Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period
AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time frame: Throughout double-blind study period (up to Day 169); table includes data up to 56 days past double-blind period or start of the open-label period, whichever occurred first.
Population: All randomized participants who received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Related SAEs | 0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | AEs | 70.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | SAEs | 3.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Related AEs | 12.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Discontinued due to SAEs | 0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Discontinued due to AEs | 0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Deaths | 0 Percentage of participants |
| Placebo | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Discontinued due to AEs | 1.8 Percentage of participants |
| Placebo | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Deaths | 1.8 Percentage of participants |
| Placebo | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | SAEs | 5.3 Percentage of participants |
| Placebo | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Related SAEs | 1.8 Percentage of participants |
| Placebo | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Discontinued due to SAEs | 1.8 Percentage of participants |
| Placebo | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | AEs | 70.2 Percentage of participants |
| Placebo | Percentage of Participants Experiencing Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), Related SAEs and AEs, and Discontinuations Due to SAEs and AEs During the Double-Blind Period | Related AEs | 15.8 Percentage of participants |
Secondary
Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169
The ACR defines ACR 50 and ACR70 response as a 50% or 70% improvement (compared with baseline values) in tender and swollen joint counts and 50% or 70% improvement in 3 of the remaining 5 core set measures (patient global assessment of pain, patient global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function) and 1 acute phase reactant value (C-reactive protein).
Time frame: At Day 169
Population: All randomized participants who received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169 | ACR 50 | 32.7 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169 | ACR 70 | 14.5 Percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169 | ACR 50 | 15.8 Percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) ACR50 and ACR70 Response at Day 169 | ACR 70 | 7.0 Percentage of participants |
Secondary
Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components
The ACR defines improvement in core components as 20%, 50%, or 70% improvement in tender and swollen joint counts and 3 of the remaining core components: patient global assessment of disease activity, physician global assessment of disease activity, patient assessment of pain, patient self-assessed disability (Health Assessment Questionnaire Disability Index \[HAQ-DI\]), and levels of 1 acute phase reactant (C-reactive protein levels or erythrocyte sedimentation rate.) The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning; scale=0 (no disability) to 3 (completely disabled); total possible score=24. The higher the score, the greater the disability.
Time frame: From Baseline to Day 169
Population: All randomized participants who received study drug and who were evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Tender Joints ≥ 20% improvement | 81.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Tender Joints ≥ 50% improvement | 66.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Tender Joints ≥ 70% improvement | 49.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Swollen Joints ≥ 20% improvement | 92.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Swollen Joints ≥ 50% improvement | 77.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Swollen Joints ≥ 70% improvement | 60.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Pain Assessment ≥ 20% improvement | 73.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Pain Assessment ≥ 50% improvement | 47.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Pain Assessment ≥ 70% improvement | 28.3 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | HAQ-DI ≥ 20% improvement | 67.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | HAQ-DI ≥ 50% improvement | 32.1 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | HAQ-DI ≥ 70% improvement | 20.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Global Assessment ≥ 20% improvement | 66.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Global Assessment ≥ 50% improvement | 39.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Global Assessment ≥ 70% improvement | 26.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Physician Global Assessment ≥ 20% improvement | 86.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Physician Global Assessment ≥ 50% improvement | 60.4 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Physician Global Assessment ≥ 70% improvement | 30.2 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | C-reactive Protein ≥ 20% improvement | 83.0 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | C-reactive Protein ≥ 50% improvement | 75.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | C-reactive Protein ≥ 70% improvement | 64.2 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | HAQ-DI ≥ 50% improvement | 23.1 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Tender Joints ≥ 20% improvement | 76.9 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | C-reactive Protein ≥ 20% improvement | 61.5 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Tender Joints ≥ 50% improvement | 50.0 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | HAQ-DI ≥ 70% improvement | 5.8 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Tender Joints ≥ 70% improvement | 23.1 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Physician Global Assessment ≥ 50% improvement | 40.4 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Swollen Joints ≥ 20% improvement | 76.9 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Global Assessment ≥ 20% improvement | 53.9 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Swollen Joints ≥ 50% improvement | 57.7 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | C-reactive Protein ≥ 70% improvement | 28.9 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Swollen Joints ≥ 70% improvement | 40.4 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Global Assessment ≥ 50% improvement | 21.2 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Pain Assessment ≥ 20% improvement | 53.9 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Physician Global Assessment ≥ 70% improvement | 19.2 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Pain Assessment ≥ 50% improvement | 23.1 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Global Assessment ≥ 70% improvement | 11.5 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Patient Pain Assessment ≥ 70% improvement | 11.5 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | C-reactive Protein ≥ 50% improvement | 53.9 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | HAQ-DI ≥ 20% improvement | 44.2 Percentage of participants |
| Placebo | Percentage of Participants With at Least 20%, 50%, or 70% Improvement From Baseline in American College of Rheumatology (ACR) Core Components | Physician Global Assessment ≥ 20% improvement | 71.2 Percentage of participants |
Secondary
Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission
EULAR defines LDAS as a disease activity score as measured by c-reactive protein (DAS28-CRP) ≤3.2 and remission as DAS28-CRP \<2.6
Time frame: At Days 169 and 1485
Population: All participants who received study drug and who were evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined remission (Day 169) | 24.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined LDAS (Day 169) | 35.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined remission(Day 1485) (n=31, 35) | 35.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined LDAS (Day 1485) (n=31, 35) | 61.3 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined remission(Day 1485) (n=31, 35) | 54.3 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined LDAS (Day 169) | 13.5 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined remission (Day 169) | 9.6 Percentage of participants |
| Placebo | Percentage of Participants With European League Against Rheumatism (EULAR)-Defined Low Disease Activity Score (LDAS) and With EULAR-defined Remission | EULAR-defined LDAS (Day 1485) (n=31, 35) | 68.6 Percentage of participants |
Secondary
Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission
LDAS is defined as a Disease Activity Score C-reactive protein (DAS28-CRP) level \<=3.2. Remission is defined as a DAS28-CRP level \<2.6.
Time frame: At Days 169, 337, 729, 1149, and 1485
Population: All participants who finished the Short-term period. n=Number of evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 169) | 35.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 337) (n=52, 51) | 51.9 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 729) (n=48, 50) | 62.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 1149) (n=44,48) | 63.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 1485) (n=31, 35) | 61.3 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 169) | 24.5 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 337) (n=52, 51) | 34.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 729) (n=48, 50) | 43.8 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 1149) (n=44,8) | 38.6 Percentage of participants |
| Abatacept, 10 mg/kg | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 1485) (n=31, 35) | 35.5 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 729) (n=48, 50) | 38.0 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 169) | 13.5 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 169) | 9.6 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 337) (n=52, 51) | 35.3 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 1485) (n=31, 35) | 54.3 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 729) (n=48, 50) | 56.0 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 337) (n=52, 51) | 23.5 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 1149) (n=44,48) | 60.4 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | Remission (Day 1149) (n=44,8) | 50.0 Percentage of participants |
| Placebo | Percentage of Participants With Low Disease Activity Score (LDAS) or Who Are in Remission | LDAS (Day 1485) (n=31, 35) | 68.6 Percentage of participants |
Secondary
Percentage of Participants With Physical Function Response as Assessed Using the Health Assessment Questionnaire Disability Index (HAQ-DI)
Improvement is measured by an improved response of at least 0.3 units from baseline on the HAQ-DI score. The HAQ-DI assesses a patient's level of functional ability via 20 questions in 8 categories of functioning. Patients respond on a scale from 0 (no disability) to 3 (completely disabled); total possible score=24. Higher score indicates greater disability. Change from baseline= postbaseline - baseline value.
Time frame: At Day 1485
Population: All participants who received study drug and who were evaluable
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept, 10 mg/kg | Percentage of Participants With Physical Function Response as Assessed Using the Health Assessment Questionnaire Disability Index (HAQ-DI) | 77.4 Percentage of participants |
| Placebo | Percentage of Participants With Physical Function Response as Assessed Using the Health Assessment Questionnaire Disability Index (HAQ-DI) | 60.0 Percentage of participants |
Secondary
Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept
Minimum concentration (Cmin) of Abatacept 500 mg and 750 mg at given time points
Time frame: At the end of infusion and 2 to 4 hours after the start of the infusion on Day 85
Population: Participants with measurement at timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept, 10 mg/kg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 85 | 17.45 μg/mL | Standard Deviation 7.442 |
| Abatacept, 10 mg/kg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 57 | 19.96 μg/mL | Standard Deviation 11.337 |
| Abatacept, 10 mg/kg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 29 | 37.76 μg/mL | Standard Deviation 10.971 |
| Abatacept, 10 mg/kg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 113 | 17.51 μg/mL | Standard Deviation 6.858 |
| Placebo | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 85 | 20.83 μg/mL | Standard Deviation 10.749 |
| Placebo | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 29 | 52.19 μg/mL | Standard Deviation 19.619 |
| Placebo | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 57 | 24.42 μg/mL | Standard Deviation 7.697 |
| Placebo | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 113 | 22.06 μg/mL | Standard Deviation 9.365 |
| Abatacept 500 mg and 750 mg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 29 | 42.30 μg/mL | Standard Deviation 15.611 |
| Abatacept 500 mg and 750 mg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 85 | 18.52 μg/mL | Standard Deviation 8.661 |
| Abatacept 500 mg and 750 mg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 113 | 18.94 μg/mL | Standard Deviation 7.936 |
| Abatacept 500 mg and 750 mg | Summary Statistics of Minimum Observed Serum Concentration (Cmin) for Abatacept | Day 57 | 21.31 μg/mL | Standard Deviation 10.504 |