Arthritis, Rheumatoid
Conditions
Brief summary
The purpose of this study is to determine whether switching to subcutaneous administration of abatacept will be safe in participants with rheumatoid arthritis who previously received long-term therapy with intravenous abatacept
Interventions
DRUGAbatacept
Subcutaneous injection, 125 mg/mL, once weekly, 48 months
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recruitment from 2 Bristol-Myers Squibb (BMS) studies (BMS IM101-029 \[NCT00048581\] and BMS IM101-102 \[NCT00048568\]). * Completion of final quarterly dosing visit in NCT00048581 or NCT00048568 as follows: US and Canadian participants: Day 1821 visit; Taiwanese participants: Day 1905 visit; Mexican participants: Day 1989 visit. * Agreement to participate in BMS IM101-185 (NCT00663702) on final quarterly dosing visit in NCT00048581 or NCT00048568 study as follows: US and Canadian participants: Day 1821 visit; Taiwanese participants: Day 1905 visit; Mexican participants: Day 1989 visit. * At the time of completion of the NCT00048581 or NCT00048568 protocol, participant did not meet any criteria requiring their discontinuation. * Drug stabilization requirements: Participants who received concomitant medications (disease-modifying antirheumatic drugs, corticosteroids, and nonsteroidal anti-inflammatory drugs) at the time of their last quarterly dosing visit for NCT00048581 or NCT00048568 were required to maintain stable dose levels from the time they signed consent until the end of the first 3 months (Day 85) of the current study. * Willingness to self-inject study medication (abatacept) or allow a caregiver to inject study medication. * Willingness to adhere to study visit schedule and comply with other protocol requirements. * Male or female (not nursing or pregnant)genders, at least 18 years of age. Women of childbearing potential (WOCBP) must have been practicing adequate contraceptive measures during the study and for up to 10 weeks after the last infusion of study medication in such a manner that the risk of pregnancy was minimized. WOCBP must have had a negative serum or urine pregnancy test result (minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 48 hours prior to the start of study medication.
Exclusion criteria
* The following treatment or therapies should not be started on or after the final quarterly dosing visit from the NCT00048581 or NCT00048568 study: Any biologic; immunoabsorption columns (such as Prosorba columns); mycophenolate mofetil; cyclosporin A or other calcineurin inhibitors; D-penicillamine; any live vaccines within 3 months of Day 1 or scheduled to receive a live vaccine during the course of the study * Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, or a concomitant medical condition that, in the opinion of the Investigator, might have placed the participation at unacceptable risk for study participation * Any clinical laboratory test result that was considered to be abnormal or not within acceptable limits on the final quarterly dosing visit of NCT00048581 or NCT00048568. Screening laboratory test results for NCT00663702 were based on the Day 1821 visit of NCT00048581 or NCT00048568 for participants enrolled at sites in the US or Canada and on the Day 1989 visit of NCT00048568 for participants enrolled at sites in Mexico. * Imprisonment or involuntarily incarceration for treatment of either a psychiatric or physical (eg, infectious disease) illness * Impairment, incapacitation, inability to complete study-related assessments, or illiteracy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Temperature | Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821 | Temperature was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early. |
| Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality | Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period | LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Sodium: \<0.95\*LLN or \>1.05\*ULN or if preRx\<LLN, \<0.95\*preRx or \>ULN, or if preRx\>ULN,\>1.05\*preRx or \<LLN. Potassium,serum: \<0.9\*LLN or \>1.1\*ULN or if preRx\<LLN, use \<0.9\*preRx or \>ULN or if preRx\>ULN, 1.1\*preRx or \<LLN. Phosphorus: 0.75\*LLN or 1.25\*ULN or, if preRx\<LLN, \<0.67\*preRx or \>ULN or, if preRx\>ULN, \<LLN. |
| Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period | LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality: . |
| Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality | Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period | preRX=pretreatment. For all values analyzed (protein, urine; glucose, urine; blood, urine: leukocyte esterase, urine; white blood cells, urine; red blood cells, urine): If missing preRx, use \>=2 or, if value \>= 4, or if preRx=0 or 0.5, use \>=2 or, if preRx= 1, use \>=3 or, if preRx=2 or 3, use \>=4. |
| Number of Participants With Adverse Events of Special Interest | Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period | AEs of special interest are AEs that may be associated with the use of immunomodulatory drugs, such as infections, malignancies, autoimmune disorders, and injection reactions (defined as local injection site reactions and systemic injection reactions occurring within 24 hours of subcutaneous injection). |
| Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821 | BP was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early. |
| Mean Heart Rate | Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821 | Heart rate was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early. |
| Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | Day 1 (Baseline) through Day 85 | An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators. Systemic injection reaction occurring ≤ 24 hours after dosing. |
| Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation | Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period | An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators. |
| Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period | LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Hemoglobin (g/dL) \>3 decrease from preRx. Hematocrit (%)\<0.75\*preRx. Erythrocytes (\*10\^6 c/uL) \<0.75\*preRx. Platelet count (\*10\^9 c/L) \<0.67\*LLN or 1.5\*ULN or, if preRx\<LLN, use \<0.5\*preRx and \<100,000 mm\^3. Leukocytes (\*10\^3 c/uL) \<0.75\*LLN or \>1.25\*ULN or, if preRx\<LLN, use \<0.8\*preRx or \>ULN or, if preRx\>ULN, use \>1.2\*preRx or \<LLN. Eosinophils \>0.750\*10\^3 c/uL. Lymphocytes \<0.750\*10\^3 c/uL or \>7.50\*10\^3 c/uL. |
| Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality | Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period | LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Alkaline phosphatase (U/L) \>2\*ULN or if preRx\>ULN, use 3\*preRx. Alanine aminotransferase (U/L)\>3\*ULN or if preRx\>ULN, use \>4\*preRx. G-glutamyl transferase (U/L)\>2\*ULN or if preRx\>ULN, use \>3\*preRx. Blood urea nitrogen (mg/dL)\>2\*preRx. Creatinine (mg/dL)\>1.5\*preRx. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With A Positive Anti-abatacept Response (Based on Enzyme-linked Immunosorbent Assay [ELISA]) at Day 85 | Day 1 (Baseline) through Day 85 | Using the ELISA, any positive (titer of 400 or greater) postbaseline sample was classified as positive immunogenicity. The percentage of participants with at least 1 positive antibody response (anti-abatacept and/or anti-CTLA4-T) during the 85 days was tabulated by antibody specificity and overall. |
| Percentage of Participants With A Positive Anti-abatacept Response (Based on Electrochemiluminescence [ECL] Immunoassay) at Day 85 | Day 1 (Baseline) through Day 85 | Number of participants was tabulated using ECL assay with at least 1 positive abatacept-induced immunogenic response (CTLA4 and possibly Ig, Ig and/or Junction Region) in the first 85 days. Positive response (titers \>10) included: * A missing baseline immunogenicity measurement and a positive immunogenicity response postbaseline * A negative baseline immunogenicity response and a positive immunogenicity response postbaseline * A positive baseline immunogenicity response and a positive immunogenicity response postbaseline that has a titer value strictly greater than the baseline titer value |
| Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 1 (Baseline) through Day 1093 | The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.) |
| Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Day 1 (Baseline) through Day 1093 | LDAS is defined as DAS 28-CRP ≤3.2. DAS 28-CRP remission is defined as DAS 28-CRP \<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.) |
| Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 1 (Baseline) to Day 1093 | The HAQ-DI assesses patients' functional ability by rating their abilities over the previous week. At least 2 questions are asked from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories is divided by the number of categories answered, yielding a score from 0-3. |
| Mean Trough Serum Concentration (Cmin) of Abatacept | Days 29, 85, 57, and 85 | Cmin of abatacept was determined from serum samples. |
Countries
Canada, Mexico, United States
Participant flow
Recruitment details
Participants were enrolled at 3 locations and 32 sites worldwide: United States (20 sites), Canada (6 sites), and Mexico (6 sites).
Pre-assignment details
A total of 126 participants were enrolled, and 3 discontinued prior to study start due to failure to continue to meet study eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| Subcutaneous Abatacept, 125 mg (Prior Anti-TNF Failure) Participants with active rheumatoid arthritis, who previously received intravenous abatacept and failed therapy with antitumor necrosis factor (anti-TNF) in an earlier study (NCT00048581, or BMS IM101-029), received subcutaneous abatacept, 125 mg, once weekly for 3 months (to Day 85). Participants received the first dose of subcutaneous abatacept within 4 weeks of the last quarterly dosing visit of the preceding intravenous abatacept study. | 52 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) Participants with active rheumatoid arthritis, who previously received intravenous abatacept and showed an inadequate response to treatment with methotrexate in an earlier study (NCT00048568,or BMS IM101-102), received subcutaneous abatacept, 125 mg, once weekly for 3 months (to Day 85). Participants received the first dose of subcutaneous abatacept within 4 weeks of the last quarterly dosing visit of the preceding intravenous abatacept study. | 71 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lack of Efficacy | 3 | 3 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Subcutaneous Abatacept, 125 mg (Prior Anti-TNF Failure) | Total | Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) |
|---|---|---|---|
| Age, Continuous | 56.5 Years STANDARD_DEVIATION 10.2 | 54.3 Years STANDARD_DEVIATION 12.5 | 52.8 Years STANDARD_DEVIATION 13.8 |
| Mean Baseline 28 Joint Disease Activity Score (DAS 28) | 3.55 Score on a scale STANDARD_DEVIATION 1.2 | 3.39 Score on a scale STANDARD_DEVIATION 1.26 | 3.28 Score on a scale STANDARD_DEVIATION 1.29 |
| Mean Baseline High Sensitivity C-Reactive Protein Level | 0.94 μg/mL STANDARD_DEVIATION 0.65 | 0.93 μg/mL STANDARD_DEVIATION 0.79 | 0.92 μg/mL STANDARD_DEVIATION 0.88 |
| Mean Number of Swollen Joints at Baseline | 5.4 Joints STANDARD_DEVIATION 6.4 | 4.8 Joints STANDARD_DEVIATION 6.1 | 4.3 Joints STANDARD_DEVIATION 5.9 |
| Mean Number of Tender Joints at Baseline | 9.1 Joints STANDARD_DEVIATION 12.8 | 8.9 Joints STANDARD_DEVIATION 12.5 | 8.8 Joints STANDARD_DEVIATION 12.4 |
| Participant Weight at Baseline 60-100 kilograms | 30 Participants | 84 Participants | 54 Participants |
| Participant Weight at Baseline Greater than 100 kilograms | 10 Participants | 13 Participants | 3 Participants |
| Participant Weight at Baseline Less than 60 kilograms | 9 Participants | 23 Participants | 14 Participants |
| Participant Weight at Baseline Missing | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 Partcipants | 1 Partcipants | 0 Partcipants |
| Race/Ethnicity, Customized Asian | 0 Partcipants | 1 Partcipants | 1 Partcipants |
| Race/Ethnicity, Customized Black/African American | 3 Partcipants | 3 Partcipants | 0 Partcipants |
| Race/Ethnicity, Customized Other | 1 Partcipants | 1 Partcipants | 0 Partcipants |
| Race/Ethnicity, Customized White | 47 Partcipants | 117 Partcipants | 70 Partcipants |
| Region of Enrollment North America | 52 Participants | 68 Participants | 16 Participants |
| Region of Enrollment South America | 0 Participants | 55 Participants | 55 Participants |
| Sex: Female, Male Female | 42 Participants | 101 Participants | 59 Participants |
| Sex: Female, Male Male | 10 Participants | 22 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 101 / 123 |
| serious Total, serious adverse events | 43 / 123 |
Outcome results
Primary
Mean Heart Rate
Heart rate was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.
Time frame: Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1 | 74.2 Beats per minute | Standard Deviation 9.56 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 29 (n=120) | 74.9 Beats per minute | Standard Deviation 8.35 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 57 (n=120) | 74.6 Beats per minute | Standard Deviation 8.63 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 85 (n=120) | 74.5 Beats per minute | Standard Deviation 8.9 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 169 (n=119) | 73.6 Beats per minute | Standard Deviation 9.05 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 253 (n=115) | 73.9 Beats per minute | Standard Deviation 9.74 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 365 (n=114) | 73.8 Beats per minute | Standard Deviation 9.37 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 449 (n=111) | 73.5 Beats per minute | Standard Deviation 9.12 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 533 (n=109) | 72.7 Beats per minute | Standard Deviation 8.41 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 617 (n=109) | 73.6 Beats per minute | Standard Deviation 9.83 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 729 (n=108) | 74.2 Beats per minute | Standard Deviation 9.71 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 813 (n=105) | 72.8 Beats per minute | Standard Deviation 7.76 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 897 (n=102) | 72.4 Beats per minute | Standard Deviation 10.05 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 981 (n=101) | 73.0 Beats per minute | Standard Deviation 8.9 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1093 (n=98) | 71.9 Beats per minute | Standard Deviation 9.07 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1177 (n=84) | 72.6 Beats per minute | Standard Deviation 8.33 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1261 (n=73) | 72.3 Beats per minute | Standard Deviation 9.41 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1345 (n=64) | 72.6 Beats per minute | Standard Deviation 8.02 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1457 (n=64) | 72.1 Beats per minute | Standard Deviation 7.78 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1541 (n=64) | 72.7 Beats per minute | Standard Deviation 8.9 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1625 (n=64) | 72.5 Beats per minute | Standard Deviation 8.73 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1709 (n=48) | 74.0 Beats per minute | Standard Deviation 9.78 |
| Subcutaneous Abatacept, 125 mg | Mean Heart Rate | Day 1821 (n=3) | 74.0 Beats per minute | Standard Deviation 6.24 |
Primary
Mean Sitting Systolic and Diastolic Blood Pressure (BP)
BP was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.
Time frame: Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 813 (n=105) | 125.6 mm Hg | Standard Deviation 16.04 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1 | 121.6 mm Hg | Standard Deviation 16.15 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 29 (n=120) | 123.6 mm Hg | Standard Deviation 16.08 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 57 (n=120) | 123.9 mm Hg | Standard Deviation 16.95 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 85 (n=120) | 124.3 mm Hg | Standard Deviation 16.62 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 169 (n=116) | 124.0 mm Hg | Standard Deviation 15.09 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 253 (n=114) | 122.3 mm Hg | Standard Deviation 14.58 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 365 (n=114) | 124.1 mm Hg | Standard Deviation 15 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 449 (n=111) | 123.9 mm Hg | Standard Deviation 15.8 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 533 (n=108) | 123.5 mm Hg | Standard Deviation 15.08 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 617 (n=109) | 124.4 mm Hg | Standard Deviation 16.03 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 729 (n=108) | 125.2 mm Hg | Standard Deviation 16.09 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 897 (n=102) | 122.8 mm Hg | Standard Deviation 13.15 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 981 (n=101) | 123.5 mm Hg | Standard Deviation 15.44 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1093 (n=98) | 122.9 mm Hg | Standard Deviation 13.46 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1177 (n=84) | 124.4 mm Hg | Standard Deviation 13.66 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1261 (n=73) | 123.0 mm Hg | Standard Deviation 15.29 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1345 (n=64) | 120.6 mm Hg | Standard Deviation 12.27 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1457 (n=64) | 124.5 mm Hg | Standard Deviation 13.17 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1541 (n=64) | 121.0 mm Hg | Standard Deviation 13.75 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1625 (n=64) | 123.4 mm Hg | Standard Deviation 14.71 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1709 (n=48) | 122.7 mm Hg | Standard Deviation 15.55 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Systolic BP Day 1821 (n=3) | 123.7 mm Hg | Standard Deviation 15.18 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1 (n=123) | 73.9 mm Hg | Standard Deviation 8.83 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 29 (n=120) | 75.6 mm Hg | Standard Deviation 9.28 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 57 (n=120) | 74.3 mm Hg | Standard Deviation 8.82 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 85 (n=120) | 74.9 mm Hg | Standard Deviation 10.37 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 169 (n=116) | 74.3 mm Hg | Standard Deviation 9.19 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 253 (n=114) | 73.9 mm Hg | Standard Deviation 9.96 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 365 (n=114) | 74.0 mm Hg | Standard Deviation 9.98 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 449 (n=111) | 74.4 mm Hg | Standard Deviation 9.53 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 533 (n=108) | 74.8 mm Hg | Standard Deviation 10.08 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 617 (n=109) | 74.9 mm Hg | Standard Deviation 9.72 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 79 (n=108) | 75.5 mm Hg | Standard Deviation 9.83 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 813 (n=105) | 75.8 mm Hg | Standard Deviation 10.2 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 897 (n=102) | 75.0 mm Hg | Standard Deviation 10.23 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 981 (n=101) | 75.2 mm Hg | Standard Deviation 9.35 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1093 (n=98) | 76.2 mm Hg | Standard Deviation 10.78 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day1177 (n=84) | 77.6 mm Hg | Standard Deviation 9.04 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1261 (n=73) | 76.3 mm Hg | Standard Deviation 9.94 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1345 (n=64) | 75.4 mm Hg | Standard Deviation 8.21 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1457 (n=64) | 76.8 mm Hg | Standard Deviation 7.14 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1541 (n=64) | 75.6 mm Hg | Standard Deviation 9.53 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1625 (n=64) | 75.6 mm Hg | Standard Deviation 9.36 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1709 (n=48) | 75.2 mm Hg | Standard Deviation 9.74 |
| Subcutaneous Abatacept, 125 mg | Mean Sitting Systolic and Diastolic Blood Pressure (BP) | Sitting Diastolic BP Day 1821 (n=3) | 69.3 mm Hg | Standard Deviation 8.14 |
Primary
Mean Temperature
Temperature was measured after the patient had been seated quietly for at least 5 minutes and recorded during the screening visit, during every office visit prior to administration of subcutaneous injections, and at study discharge or 7 days after the last dose for patients who terminated early.
Time frame: Before injection on Days 1, 29, 57, 85, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, and 1821
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1345 (n=64) | 36.3 Degrees Celsius | Standard Deviation 0.33 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1093 (n=98) | 36.3 Degrees Celsius | Standard Deviation 0.43 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1177 (n=84) | 36.3 Degrees Celsius | Standard Deviation 0.39 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1261 (n=73) | 36.3 Degrees Celsius | Standard Deviation 0.41 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1 | 36.4 Degrees Celsius | Standard Deviation 0.49 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 29 (n=120) | 36.4 Degrees Celsius | Standard Deviation 0.43 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 57 (n=120) | 36.3 Degrees Celsius | Standard Deviation 0.4 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 85 (n=120) | 36.4 Degrees Celsius | Standard Deviation 0.43 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 169 (n=119) | 36.4 Degrees Celsius | Standard Deviation 0.41 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 253 (n=115) | 36.4 Degrees Celsius | Standard Deviation 0.38 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 365 (n=114) | 36.3 Degrees Celsius | Standard Deviation 0.39 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 449 (n=111) | 36.4 Degrees Celsius | Standard Deviation 0.46 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 533 (n=109) | 36.4 Degrees Celsius | Standard Deviation 0.38 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 617 (n=109) | 36.4 Degrees Celsius | Standard Deviation 0.41 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 729 (n=108) | 36.3 Degrees Celsius | Standard Deviation 0.33 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 813 (n=105) | 36.3 Degrees Celsius | Standard Deviation 0.48 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 897 (n=102) | 36.4 Degrees Celsius | Standard Deviation 0.36 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 981 (n=101) | 36.4 Degrees Celsius | Standard Deviation 0.44 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1457 (n=64) | 36.3 Degrees Celsius | Standard Deviation 0.39 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1541 (n=64) | 36.2 Degrees Celsius | Standard Deviation 0.36 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1625 (n=64) | 36.2 Degrees Celsius | Standard Deviation 0.43 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1709 (n=48) | 36.2 Degrees Celsius | Standard Deviation 0.37 |
| Subcutaneous Abatacept, 125 mg | Mean Temperature | Day 1821 (n=3) | 36.7 Degrees Celsius | Standard Deviation 0.21 |
Primary
Number of Participants With Adverse Events of Special Interest
AEs of special interest are AEs that may be associated with the use of immunomodulatory drugs, such as infections, malignancies, autoimmune disorders, and injection reactions (defined as local injection site reactions and systemic injection reactions occurring within 24 hours of subcutaneous injection).
Time frame: Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Number of Participants With Adverse Events of Special Interest | Infections | 96 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Adverse Events of Special Interest | Malignancies | 7 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Adverse Events of Special Interest | Prespecified autoimmune disorders | 7 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Adverse Events of Special Interest | Prespecified systemic injection reactions | 14 Participants |
Primary
Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality
LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality: .
Time frame: Day 1 (Baseline) to up to 56 days past the last day of subcutaneous injection in the cumulative study period
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Protein, total, low (n=120) | 1 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Protein, total, high (n=120) | 1 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Albumin, low (n=120) | 3 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Glucose, serum, low (n=122) | 17 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Glucose, serum, high (n=122) | 12 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Glucose, serum, fasting, low (n=59) | 5 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Chemistry Laboratory Values Meeting the Criteria for Marked Abnormality | Glucose, serum, fasting, high (n=59) | 3 Participants |
Primary
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85
An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators. Systemic injection reaction occurring ≤ 24 hours after dosing.
Time frame: Day 1 (Baseline) through Day 85
Population: All participants who received at least 1 dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | Deaths | 0 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | SAEs | 1 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | Treatment-related SAEs | 0 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | SAEs leading to discontinuation | 0 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | Treatment-related AEs | 11 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | AEs leading to discontinuation | 1 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | AEIs: Infections | 20 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | AEIs: Malignancy | 0 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | AEIs: Automimmune disorders (prespecified) | 0 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | AEIs: Injection reactions (prespecified) Local | 2 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), AEs Leading to Discontinuation, and AEs of Interest (AEIs) at Day 85 | AEIs: Injection reactions (prespecified) Systemic | 2 Participants |
Primary
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation
An AE is a new or worsening illness, sign, or symptom or a clinically significant abnormal laboratory test result occurring during the study, regardless of causality, and noted by the investigators.
Time frame: Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period
Population: All participants who received at least 1 dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation | SAEs leading to discontinuation | 8 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation | Deaths | 4 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation | SAEs | 43 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation | Treatment-related SAEs | 11 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation | Treatment-related AEs | 60 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Treatment-related Adverse Events (AEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 11 Participants |
Primary
Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality
LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Sodium: \<0.95\*LLN or \>1.05\*ULN or if preRx\<LLN, \<0.95\*preRx or \>ULN, or if preRx\>ULN,\>1.05\*preRx or \<LLN. Potassium,serum: \<0.9\*LLN or \>1.1\*ULN or if preRx\<LLN, use \<0.9\*preRx or \>ULN or if preRx\>ULN, 1.1\*preRx or \<LLN. Phosphorus: 0.75\*LLN or 1.25\*ULN or, if preRx\<LLN, \<0.67\*preRx or \>ULN or, if preRx\>ULN, \<LLN.
Time frame: Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality | Sodium, serum, low (mEq/L) (n=120) | 2 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality | Potassium, serum, low (mEq/L) (n=120) | 6 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Electrolyte Laboratory Values Meeting the Criteria for Marked Abnormality | Phosphorus, inorganic, low (mg/dL) (n=120) | 2 Participants |
Primary
Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality
LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Hemoglobin (g/dL) \>3 decrease from preRx. Hematocrit (%)\<0.75\*preRx. Erythrocytes (\*10\^6 c/uL) \<0.75\*preRx. Platelet count (\*10\^9 c/L) \<0.67\*LLN or 1.5\*ULN or, if preRx\<LLN, use \<0.5\*preRx and \<100,000 mm\^3. Leukocytes (\*10\^3 c/uL) \<0.75\*LLN or \>1.25\*ULN or, if preRx\<LLN, use \<0.8\*preRx or \>ULN or, if preRx\>ULN, use \>1.2\*preRx or \<LLN. Eosinophils \>0.750\*10\^3 c/uL. Lymphocytes \<0.750\*10\^3 c/uL or \>7.50\*10\^3 c/uL.
Time frame: Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Hemoglobin, low (n=120) | 7 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Hematocrit, low (n=119) | 4 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Erythrocytes, low (n=120) | 4 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Platelet count, low (n=120) | 2 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Leukocytes, low (n=120) | 2 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Leukocytes, high (n=120) | 3 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Eosinophils (absolute), high (n=122) | 12 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Hematology Laboratory Values Meeting the Criteria for Marked Abnormality | Lymphocytes (absolute), low (n=122) | 15 Participants |
Primary
Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality
LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment. Marked abnormality criteria: Alkaline phosphatase (U/L) \>2\*ULN or if preRx\>ULN, use 3\*preRx. Alanine aminotransferase (U/L)\>3\*ULN or if preRx\>ULN, use \>4\*preRx. G-glutamyl transferase (U/L)\>2\*ULN or if preRx\>ULN, use \>3\*preRx. Blood urea nitrogen (mg/dL)\>2\*preRx. Creatinine (mg/dL)\>1.5\*preRx.
Time frame: Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality | Alkaline phosphatase, high (n=120) | 1 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality | Aspartate aminotransferase, high (n=120) | 3 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality | Alanine aminotransferase, high (n=120) | 6 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality | G-glutamyl transferase, high (n=120) | 7 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality | Blood urea nitrogen, high (n=120) | 5 Participants |
| Subcutaneous Abatacept, 125 mg | Number of Participants With Liver and Kidney Function Laboratory Values Meeting the Criteria for Marked Abnormality | Creatinine, high (n=120) | 11 Participants |
Primary
Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality
preRX=pretreatment. For all values analyzed (protein, urine; glucose, urine; blood, urine: leukocyte esterase, urine; white blood cells, urine; red blood cells, urine): If missing preRx, use \>=2 or, if value \>= 4, or if preRx=0 or 0.5, use \>=2 or, if preRx= 1, use \>=3 or, if preRx=2 or 3, use \>=4.
Time frame: Day 1 (Baseline) through 56 days past last day of subcutaneous injection in the cumulative study period
Population: All participants who received at least 1 dose of study medication. n=patients evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality | Protein, urine, high (n=122) | 12 Participants |
| Subcutaneous Abatacept, 125 mg | Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality | Glucose, urine, high (n=122) | 8 Participants |
| Subcutaneous Abatacept, 125 mg | Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality | Blood, urine, high (n=122) | 28 Participants |
| Subcutaneous Abatacept, 125 mg | Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality | Leukocyte esterase, urine, high (n=95) | 32 Participants |
| Subcutaneous Abatacept, 125 mg | Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality | White blood cells, urine, high (n=103) | 64 Participants |
| Subcutaneous Abatacept, 125 mg | Participants With Urinalysis Values Meeting the Criteria for Marked Abnormality | Red blood cells, urine, high (n=91) | 33 Participants |
Secondary
Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Time frame: Day 1 (Baseline) through Day 1093
Population: All participants who received at least 1 dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 29 (n=50, 69) | 3.60 Units on a scale | Standard Deviation 1.24 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 57 (n=49, 69) | 3.36 Units on a scale | Standard Deviation 1.11 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 85 (n=49, 70) | 3.44 Units on a scale | Standard Deviation 1.14 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 169 (n=48, 71) | 3.45 Units on a scale | Standard Deviation 1.1 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 253 (n=46, 71) | 3.60 Units on a scale | Standard Deviation 1.33 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 365 (n=45, 70) | 3.51 Units on a scale | Standard Deviation 1.32 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 449 (n=43, 69) | 3.58 Units on a scale | Standard Deviation 1.33 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 533 (n=43, 68) | 3.51 Units on a scale | Standard Deviation 1.23 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 617 (n=41, 67) | 3.31 Units on a scale | Standard Deviation 1.2 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 729 (n=41, 67) | 3.30 Units on a scale | Standard Deviation 1.12 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 813 (n=39, 65) | 3.38 Units on a scale | Standard Deviation 1.17 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 897 (n=38, 65) | 3.41 Units on a scale | Standard Deviation 1.46 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 981 (n=38, 65) | 3.32 Units on a scale | Standard Deviation 1.37 |
| Subcutaneous Abatacept, 125 mg | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 1093 (n=34, 65) | 3.21 Units on a scale | Standard Deviation 1.26 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 813 (n=39, 65) | 2.81 Units on a scale | Standard Deviation 1.05 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 29 (n=50, 69) | 2.95 Units on a scale | Standard Deviation 1.31 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 533 (n=43, 68) | 3.08 Units on a scale | Standard Deviation 1.43 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 57 (n=49, 69) | 2.96 Units on a scale | Standard Deviation 1.37 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 981 (n=38, 65) | 3.02 Units on a scale | Standard Deviation 1.28 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 85 (n=49, 70) | 2.91 Units on a scale | Standard Deviation 1.3 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 617 (n=41, 67) | 3.16 Units on a scale | Standard Deviation 1.37 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 169 (n=48, 71) | 2.93 Units on a scale | Standard Deviation 1.29 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 897 (n=38, 65) | 3.02 Units on a scale | Standard Deviation 1.19 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 253 (n=46, 71) | 3.01 Units on a scale | Standard Deviation 1.21 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 729 (n=41, 67) | 3.15 Units on a scale | Standard Deviation 1.26 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 365 (n=45, 70) | 3.09 Units on a scale | Standard Deviation 1.25 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 1093 (n=34, 65) | 3.10 Units on a scale | Standard Deviation 1.37 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Scores Over Time | Day 449 (n=43, 69) | 3.21 Units on a scale | Standard Deviation 1.35 |
Secondary
Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time
The HAQ-DI assesses patients' functional ability by rating their abilities over the previous week. At least 2 questions are asked from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories is divided by the number of categories answered, yielding a score from 0-3.
Time frame: Day 1 (Baseline) to Day 1093
Population: All participants who received at least 1 dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 533 (n=43, 68) | 1.07 Units on a scale | Standard Deviation 0.71 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 169 (n=49, 71) | 0.97 Units on a scale | Standard Deviation 0.67 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 617 (n=42, 67) | 0.99 Units on a scale | Standard Deviation 0.74 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 29 (n=51, 69) | 0.98 Units on a scale | Standard Deviation 0.7 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 729 (n=42, 67) | 0.98 Units on a scale | Standard Deviation 0.74 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 253 (n=48, 71) | 0.97 Units on a scale | Standard Deviation 0.69 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 813 (n=40, 66) | 1.02 Units on a scale | Standard Deviation 0.74 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 85 (n=49, 71) | 0.92 Units on a scale | Standard Deviation 0.67 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 897 (n=39, 65) | 1.06 Units on a scale | Standard Deviation 0.75 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 365 (n=46, 70) | 0.96 Units on a scale | Standard Deviation 0.66 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 981 (n=39, 65) | 1.02 Units on a scale | Standard Deviation 0.76 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 57 (n=50, 71) | 0.92 Units on a scale | Standard Deviation 0.68 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 1093 (n=34, 65) | 0.96 Units on a scale | Standard Deviation 0.74 |
| Subcutaneous Abatacept, 125 mg | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 449 (n=43, 69) | 0.97 Units on a scale | Standard Deviation 0.75 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 1093 (n=34, 65) | 0.92 Units on a scale | Standard Deviation 0.74 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 29 (n=51, 69) | 0.80 Units on a scale | Standard Deviation 0.67 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 57 (n=50, 71) | 0.80 Units on a scale | Standard Deviation 0.67 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 85 (n=49, 71) | 0.82 Units on a scale | Standard Deviation 0.69 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 169 (n=49, 71) | 0.87 Units on a scale | Standard Deviation 0.74 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 253 (n=48, 71) | 0.87 Units on a scale | Standard Deviation 0.73 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 365 (n=46, 70) | 0.85 Units on a scale | Standard Deviation 0.69 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 533 (n=43, 68) | 0.94 Units on a scale | Standard Deviation 0.71 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 617 (n=42, 67) | 0.87 Units on a scale | Standard Deviation 0.69 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 729 (n=42, 67) | 0.90 Units on a scale | Standard Deviation 0.71 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 813 (n=40, 66) | 0.88 Units on a scale | Standard Deviation 0.68 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 897 (n=39, 65) | 0.89 Units on a scale | Standard Deviation 0.73 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 981 (n=39, 65) | 0.91 Units on a scale | Standard Deviation 0.69 |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) Scores Over Time | Day 449 (n=43, 69) | 0.89 Units on a scale | Standard Deviation 0.69 |
Secondary
Mean Trough Serum Concentration (Cmin) of Abatacept
Cmin of abatacept was determined from serum samples.
Time frame: Days 29, 85, 57, and 85
Population: All participants who received at least 1 dose of study medication. n=patients who had at least 1 pharmacokinetic sample drawn postbaseline
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Mean Trough Serum Concentration (Cmin) of Abatacept | Day 29 (n=116) | 34.31 μg/mL | Geometric Coefficient of Variation 46 |
| Subcutaneous Abatacept, 125 mg | Mean Trough Serum Concentration (Cmin) of Abatacept | Day 57 (n=117) | 34.25 μg/mL | Geometric Coefficient of Variation 48 |
| Subcutaneous Abatacept, 125 mg | Mean Trough Serum Concentration (Cmin) of Abatacept | Day 85 (n=118) | 33.78 μg/mL | Geometric Coefficient of Variation 48 |
Secondary
Percentage of Participants With A Positive Anti-abatacept Response (Based on Electrochemiluminescence [ECL] Immunoassay) at Day 85
Number of participants was tabulated using ECL assay with at least 1 positive abatacept-induced immunogenic response (CTLA4 and possibly Ig, Ig and/or Junction Region) in the first 85 days. Positive response (titers \>10) included: * A missing baseline immunogenicity measurement and a positive immunogenicity response postbaseline * A negative baseline immunogenicity response and a positive immunogenicity response postbaseline * A positive baseline immunogenicity response and a positive immunogenicity response postbaseline that has a titer value strictly greater than the baseline titer value
Time frame: Day 1 (Baseline) through Day 85
Population: All participants who received at least 1 subcutaneous abatacept injection and who had at least 1 immunogenicity result reported (on the corresponding assay) on subcutaneous abatacept treatment. n=patients evaluable
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With A Positive Anti-abatacept Response (Based on Electrochemiluminescence [ECL] Immunoassay) at Day 85 | 0 Percentage of participants |
Secondary
Percentage of Participants With A Positive Anti-abatacept Response (Based on Enzyme-linked Immunosorbent Assay [ELISA]) at Day 85
Using the ELISA, any positive (titer of 400 or greater) postbaseline sample was classified as positive immunogenicity. The percentage of participants with at least 1 positive antibody response (anti-abatacept and/or anti-CTLA4-T) during the 85 days was tabulated by antibody specificity and overall.
Time frame: Day 1 (Baseline) through Day 85
Population: All participants who received at least 1 subcutaneous abatacept injection and who had at least 1 immunogenicity result reported (on the corresponding assay) on subcutaneous abatacept treatment. n=patients evaluable
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With A Positive Anti-abatacept Response (Based on Enzyme-linked Immunosorbent Assay [ELISA]) at Day 85 | Anti-abatacept (n=85) | 8.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With A Positive Anti-abatacept Response (Based on Enzyme-linked Immunosorbent Assay [ELISA]) at Day 85 | Anti-CTLA4-T9 (n=122) | 0.8 Percentage of participants |
Secondary
Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time:
LDAS is defined as DAS 28-CRP ≤3.2. DAS 28-CRP remission is defined as DAS 28-CRP \<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), C-reactive protein level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
Time frame: Day 1 (Baseline) through Day 1093
Population: All participants who received at least 1 dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 533 (n=43, 68) | 37.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 85 (n=49, 70) | 40.8 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 533 (n=43, 68) | 23.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 253 (n=46, 71) | 39.1 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 617 (n=41, 67) | 46.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 29 (n=50, 69) | 24.0 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 617 (n=41, 67) | 29.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 253 (n=46, 71) | 30.4 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 729 (n=41, 67) | 41.5 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 85 (n=49, 70) | 24.5 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 729 (n=41, 67) | 29.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 365 (n=45, 70) | 40.0 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 813 (n=39, 65) | 43.6 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 57 (n=49, 69) | 26.5 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 813 (n=39, 65) | 25.6 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 365 (n=45, 70) | 33.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 897 (n=38, 65) | 50.0 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 169 (n=48, 71) | 39.6 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 897 (n=38, 65) | 34.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 449 (n=43, 69) | 41.9 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | DLAS Day 981 (n=38, 65) | 50.0 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 57 (n=49, 69) | 44.9 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 981 (n=38, 65) | 42.1 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 449 (n=43, 69) | 30.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 1093 (n=34, 65) | 52.9 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 169 (n=48, 71) | 25.0 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 1093 (n=34, 65) | 41.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 29 (n=50, 69) | 40.0 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 1093 (n=34, 65) | 50.8 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 29 (n=50, 69) | 68.1 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 29 (n=50, 69) | 50.7 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 57 (n=49, 69) | 60.9 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 57 (n=49, 69) | 47.8 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 85 (n=49, 70) | 64.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 85 (n=49, 70) | 48.6 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 169 (n=48, 71) | 59.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 169 (n=48, 71) | 49.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 253 (n=46, 71) | 66.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 253 (n=46, 71) | 42.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 365 (n=45, 70) | 57.1 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 365 (n=45, 70) | 42.9 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 449 (n=43, 69) | 53.6 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 449 (n=43, 69) | 43.5 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 533 (n=43, 68) | 60.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 533 (n=43, 68) | 48.5 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 617 (n=41, 67) | 53.7 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 617 (n=41, 67) | 43.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 729 (n=41, 67) | 59.7 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 729 (n=41, 67) | 34.3 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 813 (n=39, 65) | 69.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 813 (n=39, 65) | 46.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 897 (n=38, 65) | 60.0 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 897 (n=38, 65) | 43.1 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | DLAS Day 981 (n=38, 65) | 64.6 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | Remission Day 981 (n=38, 65) | 46.2 Percentage of participants |
| Subcutaneous Abatacept, 125 mg (Prior Methotrexate Failure) | Percentage of Participants With Low Disease Activity Score (LDAS) and Disease Activity Score 28 Based on C-reactive Protein (DAS 28-CRP) Remission Over Time: | LDAS Day 1093 (n=34, 65) | 58.5 Percentage of participants |