Rheumatoid Arthritis (RA)
Conditions
Brief summary
The purpose of this study is to determine whether a weekly subcutaneous dose of abatacept yields clinical efficacy comparable to that of monthly intravenous doses of abatacept in participants with rheumatoid arthritis and an inadequate response to current methotrexate therapy.
Interventions
Participants received 125 mg weekly SC abatacept injections (with an intravenous \[IV\] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment.
Participants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo). 500mg (for body weight up to 60 kg) 750 mg (body weight between 61 and 100 kg) 1g (body weight above 100 kg)infusions
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
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Subjects who are considered methotrexate inadequate responders * 10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)
Exclusion criteria
* Subjects who failed one or multiple anti-tumor necrosis factor (TNF) therapies * Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematous) * Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules) * Subjects with severe chronic or recurrent bacterial infections * Subjects who have received treatment with rituximab An Anti-TNF Failure Sub-study was initiated (recruited separately from Main study) using the same treatment as the Main study in order to assess the immunogenicity and safety in the Anti-TNF Failure population. The Sub-study terminated due to low recruitment and participants were permitted to roll into the LT Open Label Period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169 | Day 169 | The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline 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 acute phase reactant value (C-reactive protein). |
| Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Days 85, and 169 and postvisits on Days 28, 56, and 85 | Serum samples from all treated adult participants with active rheumatoid arthritis who were from the Anti-TNF failure population were screened for the presence of drug-specific antibodies using Enzyme Linked Immunoabsorbant Assay (ELISA). The number of participants who had the presence of anti-abatacept antibodies or anti-CTLA-4 antibodies present in their serum are summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI | Baseline to Day 169 | The HAQ-DI includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from 0 to a maximum overall score of 3.0. |
| Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169 | Day 169 | The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ-DI response=an improvement of at least 0.3 units from baseline in HAQ-DI. |
| Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first. | AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. 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 development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug |
| Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died | Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first. | AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. 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 development of drug dependency or drug abuse, is an important medical event. |
| Double-blind Period: Number of Participants With AEs of Special Interest | Day 1 up to 56 days post last dose in short- term period or first dose in the long -term period, whichever occurs 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. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections,serious infections,and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (prespecified AEs occurring within 1 hr of start of infusion), peri-infusional AEs (prespecified AEs occurring within 24 hrs of the start of infusion), system injection reactions, and local injection site reactions |
| Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements | Day 1 through end of short-term period (Day 169) | Vital sign measurements were performed for participants before and after infusion/subcutaneous injection of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator. |
| Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Day 1 through end of short-term period (Day 169) | ULN=upper limit of normal; LLN=lower limit of normal; BL= baseline. Marked abnormality criteria: Hemoglobin: \>3 g/dL decrease from BL; hematocrit: \<0.75\*BL; erythrocytes: \<0.75\*BL; platelets: \<0.67\*LLN/\>1.5\*ULN, or if BL\<LLN, use \<0.5\*BL and \<100,000 mm\^3; leukocytes: \<0.75\*LLN/\>1.25\*ULN, or if BL\<LLN use \<0.8\*BL or \>ULN, or if BL\>ULN, use \>1.2\*BL or \<LLN; neutrophils+bands: \<1.0\*10\^3 c/uL; eosinophils: \>0.750\*10\^3 c/uL; basophils: \>400 mm\^3; monocytes: \>2000 mm\^3; lymphocytes: \<0.750\*10\^3 c/uL/\>7.50\*10\^3 c/uL. |
| Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | Day 1 through end of short-term period (Day 169) | Marked abnormality criteria: Alkaline phosphatase (ALP): \>2\*ULN, or if BL\>ULN, use \>3\*BL; aspartate aminotransferase (AST): \>3\*ULN, or if BL\>ULN, use \>4\*BL; alanine aminotransferase (ALT): \>3\*ULN, or if BL\>ULN, use \>4\*BL; G-glutamyl transferase (GGT): \>2\* ULN, or if BL\>ULN, use \>3\*BL; bilirubin: \>2\* ULN, or if BL\>ULN, use \>4\*BL; blood urea nitrogen: \>2\* BL; creatinine: \>1.5\*BL |
| Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Day 1 through end of short-term period (Day 169) | Marked abnormality criteria: Sodium: \<0.95\*LLN/\>1.05\*ULN, or if BL\<LLN, use \<0.95\* BL or \>ULN, or if BL\>ULN, use\>1.05\* BL or \<LLN; potassium: \<0.9\* LLN/\>1.1\*ULN, or if BL\<LLN then use \<0.9\* BL or \>ULN, or if BL\>ULN, use\>1.1\* BL or \<LLN; chlorine: \<0.9\*LLN/\>1.1\* ULN, or if BL\<LLN, use \<0.9\*BL or \>ULN, or if BL\>ULN, use\>1.1\*BL or \<LLN; calcium: \<0.8\* LLN/\>1.2\* ULN, or if BL\<LLN, use \<0.75\*BL or \>ULN, or if BL\>ULN, use\>1.25\* BL or \<LLN; phosphorous: \<0.75\* LLN/\>1.25\*ULN, or if BL\<LLN, use 0.67\*BL or \>ULN, or if BL\>ULN, use\>1.33\* BL or \<LLN |
| Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Days 57, 85, 113, 120, 127, 134, 141, and 169 | — |
| Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Days 57, 85, 113, 120, 127, 134, 141, and 169 (ST Period) | Serum concentrations of abatacept were analyzed using a validated ELISA. Steady-state trough observed concentration in serum (Cminss) was measured in μg/mL. Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169. |
| Double-blind Period: Maximum Observed Serum Concentration of Abatacept | End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous | — |
| Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept | End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous | Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169. Cmax was measured in micrograms per milliliter (μg/mL). |
| Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept | Dosing interval between Days 113 and 141 (TAU=28 days) | — |
| Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169 | Day 169 | The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% improvement from baseline 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 acute phase reactant value (C-reactive protein). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures. |
| Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Days 85, and 169 and postvisits on Days 28, 56, and 85 | Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept (anti-ABA) or anti-CTLA4 antibody (anti-CTLA4). |
| Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Baseline to Days 15, 29, 57, 85, 113, 141, and 169 | C-reactive protein is an acute phase reactant protein that is a clinical marker for rheumatoid arthritis. Time-matched median percent change from baseline= (time-matched baseline value - Post-baseline value)/time-matched baseline value\*100, where the time-matched baseline value represents the median baseline value for only that cohort of participants with measurements available at that visit. |
| Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Days 85, and 169 and postvisits on Days 28, 56, and 85 | An electrochemiluminescence immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; abatacept molecule). Ig and/or Junction (JNCT) category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a postbaseline titer higher than Baseline, or any postbaseline positivity if Baseline value was missing. Trt=treatment. |
| Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline to Day 169 | Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process. |
| Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821 | Days 169, 729, 1261, 1821 | The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline 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 acute phase reactant value (C-reactive protein). |
| Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Days 169, 729, 1261, 1821 | The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% improvement from baseline 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 acute phase reactant value (C-reactive protein). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures. |
| Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821 | Days 169, 729, 1261, 1821 | The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from very good to very bad). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6. A clinically significant response= decrease in DAS28 score of \>1.2 from baseline. |
| Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821 | Days 169, 729, 1261, 1821 | The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from very good to very bad). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6. |
| Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821 | Days 169, 729, 1261, 1821 | The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from very good to very bad). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6. |
| Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821 | Days 169, 729, 1261, 1821 | The disability section of the full HAQ includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI overall score ranges from a minimum of 0 to a maximum of 3.0. HAQ response was defined as an improvement (reduction) from baseline (Day 1) of at least 0.3 units in the HAQ score. |
| Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014) | AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. 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 development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug |
| Open-Label LT Period: Number of Participants With AEs of Special Interest | End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014) | AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections, serious infections, and opportunistic infections; autoimmune disorders; malignancies; system injection reactions, and local injection site reactions. |
| Open-Label LT Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements | End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014) | Vital sign assessments were performed in the LT period at 12-week intervals and at a yearly visit (at 16-week intervals) and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Vital signs included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator. |
| Open-Label LT Period: Number of Participants With Clinically Significant Laboratory Abnormalities | End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014) | Laboratory assessments were performed in the LT period at 12-week intervals and at a yearly visit and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Abnormalities were determined to be clinically significant by the investigator. |
| Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept | Dosing Interval between Days 113 and 141 (TAU=28 days) | Serum concentrations of abatacept were analyzed using a validated ELISA. AUC(TAU) was measured as μg\*h/mL. Samples for AUC (TAU) were obtained on Days 113, 120, 127, 134, and 141. |
| Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169 | Day 169 | The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hungary, India, Ireland, Italy, Mexico, Netherlands, Peru, Poland, Russia, South Africa, South Korea, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
During the double blind short term (ST) period of the Main study, a sub-study in RA participants was initiated to evaluate anti-tumor necrosis factor (TNF) failure population. The sub-study was terminated early due to slow recruitment and participants from the sub-study were allowed to roll into the Main study during the LT Open Label Period.
Pre-assignment details
2492 enrolled: 2472 in Main Study:1008 not randomized: 918 no longer met criteria, 61 withdrew consent, 7 lost to follow-up, 22 other reasons. Randomized, not treated: 4 no longer met criteria, 2 withdrew consent, and 1 randomization error; 20 enrolled in Anti-TNF sub-study; 2 not randomized as no longer met criteria; 18 randomized in substudy.
Participants by arm
| Arm | Count |
|---|---|
| Subcutaneous (SC) Abatacept Participants received 125 mg weekly SC abatacept injections (with an intravenous \[IV\] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment. The Per Protocol (PP) Analysis Population (instead of the Intent-To-Treat Population) was used to perform primary and key secondary efficacy analyses as per regulatory guidelines for non-inferiority studies. | 696 |
| Intravenous (IV) Abatacept Participants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo). The Per Protocol (PP) Analysis Population (instead of the Intent-To-Treat Population) was used to perform primary and key secondary efficacy analyses as per regulatory guidelines for non-inferiority studies. | 683 |
| Total | 1,379 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Anti-TNF Sub-Study in ST Period | Lack of Efficacy | 1 | 1 |
| Double Blind ST Period Main Study | Administrative Reason By Sponsor | 1 | 0 |
| Double Blind ST Period Main Study | Adverse Event | 17 | 25 |
| Double Blind ST Period Main Study | Death | 1 | 1 |
| Double Blind ST Period Main Study | Early Discontinuation | 0 | 1 |
| Double Blind ST Period Main Study | Incomplete Breast Exam | 0 | 1 |
| Double Blind ST Period Main Study | Investigator Decision | 0 | 1 |
| Double Blind ST Period Main Study | Lack of Efficacy | 6 | 1 |
| Double Blind ST Period Main Study | Lost to Follow-up | 0 | 6 |
| Double Blind ST Period Main Study | Missed Doses | 0 | 1 |
| Double Blind ST Period Main Study | No Longer Meets Study Criteria | 2 | 1 |
| Double Blind ST Period Main Study | Ongoing Infection Risk | 1 | 0 |
| Double Blind ST Period Main Study | Participant Weight Gain | 1 | 0 |
| Double Blind ST Period Main Study | Participant Withdrew-Recurrent Infection | 0 | 1 |
| Double Blind ST Period Main Study | Poor/Non-Compliance | 3 | 0 |
| Double Blind ST Period Main Study | Suspended Drug Due To Surgery | 0 | 1 |
| Double Blind ST Period Main Study | Withdrawal by Subject | 11 | 5 |
| Open Label LT Period Main + Sub-Study | Administrative reason by Sponsor | 9 | 0 |
| Open Label LT Period Main + Sub-Study | Adverse Event | 100 | 0 |
| Open Label LT Period Main + Sub-Study | Death | 20 | 0 |
| Open Label LT Period Main + Sub-Study | Lack of Efficacy | 89 | 0 |
| Open Label LT Period Main + Sub-Study | Lost to Follow-up | 32 | 0 |
| Open Label LT Period Main + Sub-Study | no end of study status page | 1 | 0 |
| Open Label LT Period Main + Sub-Study | No longer met criteria | 1 | 0 |
| Open Label LT Period Main + Sub-Study | non-specified | 71 | 0 |
| Open Label LT Period Main + Sub-Study | Poor/non-compliance | 8 | 0 |
| Open Label LT Period Main + Sub-Study | Pregnancy | 16 | 0 |
| Open Label LT Period Main + Sub-Study | Withdrawal by Subject | 81 | 0 |
Baseline characteristics
| Characteristic | Total | Intravenous (IV) Abatacept | Subcutaneous (SC) Abatacept |
|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 12.8 | 49.9 years STANDARD_DEVIATION 12.7 | 49.9 years STANDARD_DEVIATION 13 |
| Baseline Methotrexate (MTX) Dose | 16.4 mg/wk STANDARD_DEVIATION 3.6 | 16.5 mg/wk STANDARD_DEVIATION 3.7 | 16.3 mg/wk STANDARD_DEVIATION 3.6 |
| Baseline Weight Category >100 kg | 104 participants | 47 participants | 57 participants |
| Baseline Weight Category <60 kg | 346 participants | 171 participants | 175 participants |
| Baseline Weight Category 60 to 100 kg | 929 participants | 465 participants | 464 participants |
| Disease Activity Score (CRP) | 6.24 units on a scale STANDARD_DEVIATION 0.83 | 6.22 units on a scale STANDARD_DEVIATION 0.83 | 6.25 units on a scale STANDARD_DEVIATION 0.84 |
| Duration of Disease Category > 10 yrs | 366 participants | 177 participants | 189 participants |
| Duration of Disease Category 2 - ≤5 yrs | 289 participants | 145 participants | 144 participants |
| Duration of Disease Category ≤2 Years | 435 participants | 206 participants | 229 participants |
| Duration of Disease Category 5 - ≤10 yrs | 289 participants | 155 participants | 134 participants |
| Duration of RA Disease | 7.7 years STANDARD_DEVIATION 7.9 | 7.7 years STANDARD_DEVIATION 7.9 | 7.6 years STANDARD_DEVIATION 8 |
| High Sensitivity C-Reactive Protein (hsCRP) Level | 2.69 mg/dL STANDARD_DEVIATION 2.91 | 2.72 mg/dL STANDARD_DEVIATION 2.91 | 2.65 mg/dL STANDARD_DEVIATION 2.91 |
| Number of Swollen Joints | 20.0 swollen joints STANDARD_DEVIATION 9 | 19.6 swollen joints STANDARD_DEVIATION 8.5 | 20.5 swollen joints STANDARD_DEVIATION 9.4 |
| Number of Tender Joints | 29.6 tender joints STANDARD_DEVIATION 13.6 | 29.2 tender joints STANDARD_DEVIATION 13.1 | 30 tender joints STANDARD_DEVIATION 14.1 |
| Participant Global Assessment | 66.2 units on a scale STANDARD_DEVIATION 20 | 65.2 units on a scale STANDARD_DEVIATION 19.9 | 67.2 units on a scale STANDARD_DEVIATION 20.1 |
| Participant Pain Assessment | 67.5 units on a scale STANDARD_DEVIATION 20.3 | 66.9 units on a scale STANDARD_DEVIATION 20.5 | 68.0 units on a scale STANDARD_DEVIATION 20 |
| Physical Function (Health Assessment Questionnaire Disability Index [HAQ-DI]) | 1.71 units on a scale STANDARD_DEVIATION 0.67 | 1.69 units on a scale STANDARD_DEVIATION 0.67 | 1.73 units on a scale STANDARD_DEVIATION 0.68 |
| Physician Global Assessment | 63.9 units on a scale STANDARD_DEVIATION 16.4 | 63.4 units on a scale STANDARD_DEVIATION 16.3 | 64.3 units on a scale STANDARD_DEVIATION 16.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 135 Participants | 72 Participants | 63 Participants |
| Race (NIH/OMB) Black or African American | 50 Participants | 24 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 167 Participants | 81 Participants | 86 Participants |
| Race (NIH/OMB) White | 1021 Participants | 505 Participants | 516 Participants |
| Region Of Enrollment Europe | 246 participants | 123 participants | 123 participants |
| Region Of Enrollment North America | 240 participants | 111 participants | 129 participants |
| Region Of Enrollment Rest of the World | 215 participants | 109 participants | 106 participants |
| Region Of Enrollment South America | 678 participants | 340 participants | 338 participants |
| Rheumatoid Factor Status Negative | 193 participants | 91 participants | 102 participants |
| Rheumatoid Factor Status Positive | 1165 participants | 583 participants | 582 participants |
| Rheumatoid Factor Status Unknown | 21 participants | 9 participants | 12 participants |
| Sex: Female, Male Female | 1135 Participants | 549 Participants | 586 Participants |
| Sex: Female, Male Male | 244 Participants | 134 Participants | 110 Participants |
| Weight | 71.8 kg STANDARD_DEVIATION 17.8 | 71.5 kg STANDARD_DEVIATION 17.5 | 72.1 kg STANDARD_DEVIATION 18.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 544 / 731 | 567 / 744 |
| serious Total, serious adverse events | 206 / 731 | 199 / 744 |
Outcome results
Primary
Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population
Serum samples from all treated adult participants with active rheumatoid arthritis who were from the Anti-TNF failure population were screened for the presence of drug-specific antibodies using Enzyme Linked Immunoabsorbant Assay (ELISA). The number of participants who had the presence of anti-abatacept antibodies or anti-CTLA-4 antibodies present in their serum are summarized.
Time frame: Days 85, and 169 and postvisits on Days 28, 56, and 85
Population: All randomized participants in the Anti-TNF Failure Sub-study who received at least 1 dose of study medication. n=Number of participants with at least 1 assessment available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 169 Anti-CTLA4-T(n=6,9) | 1 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 85 days post Anti-abatacept (n=0,1) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 85 Anti-abatacept (n=8,10) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 85 Anti-CTLA4-T (n=8,10) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 169 Anti-abatacept (n=6,9) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Overall Treatment Anti-abatacept (n=8,10) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Overall on Treatment Anti-CTLA4-T(n=8,10) | 1 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 28 days post Anti-abatacept (n=1,1) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 28 days post Anti-CTLA4-T (n=1,1) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 56 days post Anti-abatacept (n=0,1) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 56 days post Anti-CTLA4-T (n=0,1) | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 85 days post Anti-CTLA4-T (n=0,1) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 56 days post Anti-abatacept (n=0,1) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Overall on Treatment Anti-CTLA4-T(n=8,10) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 85 days post Anti-CTLA4-T (n=0,1) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 28 days post Anti-abatacept (n=1,1) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 85 Anti-abatacept (n=8,10) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 56 days post Anti-CTLA4-T (n=0,1) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 85 Anti-CTLA4-T (n=8,10) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 28 days post Anti-CTLA4-T (n=1,1) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 169 Anti-abatacept (n=6,9) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Day 169 Anti-CTLA4-T(n=6,9) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | 85 days post Anti-abatacept (n=0,1) | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population | Overall Treatment Anti-abatacept (n=8,10) | 0 participants |
Primary
Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline 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 acute phase reactant value (C-reactive protein).
Time frame: Day 169
Population: Per protocol (PP) population, defined as participants who are compliant with the study criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169 | 527 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169 | 514 participants |
Secondary
Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept
Serum concentrations of abatacept were analyzed using a validated ELISA. AUC(TAU) was measured as μg\*h/mL. Samples for AUC (TAU) were obtained on Days 113, 120, 127, 134, and 141.
Time frame: Dosing Interval between Days 113 and 141 (TAU=28 days)
Population: Participants in the sub-study who received at least 1 dose of study medication and who had adequate PK profiles for analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept | 4384.80 μg*h/mL | Geometric Coefficient of Variation 17 |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept | 34260.55 μg*h/mL | Geometric Coefficient of Variation 35 |
Secondary
Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept
Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169. Cmax was measured in micrograms per milliliter (μg/mL).
Time frame: End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous
Population: Participants in the Sub-study who received at least 1 dose of study medication and who had adequate PK profiles were analyzed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Abatacept | Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept | 35.84 μg/mL | Geometric Coefficient of Variation 24 |
| Intravenous Abatacept | Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept | 229.88 μg/mL | Geometric Coefficient of Variation 26 |
Secondary
Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept
Serum concentrations of abatacept were analyzed using a validated ELISA. Steady-state trough observed concentration in serum (Cminss) was measured in μg/mL. Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169.
Time frame: Days 57, 85, 113, 120, 127, 134, 141, and 169 (ST Period)
Population: Participants who received at least 1 dose of study medication and who had adequate PK profiles were analyzed. n= number of participants available at each specific time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 85 (n=6,9) | 21.51 μg/mL | Geometric Coefficient of Variation 26 |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 127 (n=3) | 25.42 μg/mL | Geometric Coefficient of Variation 9 |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 57 (n=3,4) | 25.53 μg/mL | Geometric Coefficient of Variation 16 |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 134 (n=3) | 25.55 μg/mL | Geometric Coefficient of Variation 13 |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 113 (n=6,6) | 23.14 μg/mL | Geometric Coefficient of Variation 27 |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 141 (n=4,6) | 20.85 μg/mL | Geometric Coefficient of Variation 24 |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 120 (n=4) | 25.75 μg/mL | Geometric Coefficient of Variation 17 |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 169 (n=5,7) | 19.66 μg/mL | Geometric Coefficient of Variation 25 |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 120 (n=4) | NA μg/mL | — |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 85 (n=6,9) | 12.50 μg/mL | Geometric Coefficient of Variation 48 |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 113 (n=6,6) | 11.10 μg/mL | Geometric Coefficient of Variation 31 |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 169 (n=5,7) | 9.00 μg/mL | Geometric Coefficient of Variation 53 |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 57 (n=3,4) | 15.51 μg/mL | Geometric Coefficient of Variation 25 |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 127 (n=3) | NA μg/mL | — |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 134 (n=3) | NA μg/mL | — |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept | Day 141 (n=4,6) | 8.34 μg/mL | Geometric Coefficient of Variation 44 |
Secondary
Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died
AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. 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 development of drug dependency or drug abuse, is an important medical event.
Time frame: Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died | Deaths | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died | SAEs | 0 participants |
| Subcutaneous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died | AEs Leading to Discontinuation | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died | Deaths | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died | SAEs | 0 participants |
| Intravenous Abatacept | Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died | AEs Leading to Discontinuation | 0 participants |
Secondary
Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI
The HAQ-DI includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from 0 to a maximum overall score of 3.0.
Time frame: Baseline to Day 169
Population: All participants who received at least 1 dose of study medication at any time and had HAD-QI scores available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI | -0.69 units on a scale | Standard Error 0.02 |
| Intravenous Abatacept | Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI | -0.70 units on a scale | Standard Error 0.02 |
Secondary
Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept
Time frame: Dosing interval between Days 113 and 141 (TAU=28 days)
Population: Participants who received at least 1 dose of study medication and who had adequate PK profiles for analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept | 5182.37 µg*h/mL | Standard Deviation 2854.136 |
| Intravenous Abatacept | Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept | 39587.08 µg*h/mL | Standard Deviation 15444.743 |
Secondary
Double-blind Period: Maximum Observed Serum Concentration of Abatacept
Time frame: End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous
Population: Participants who received at least 1 dose of study medication and who had adequate PK profiles for analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Maximum Observed Serum Concentration of Abatacept | 40.39 µg/mL | Standard Deviation 30.148 |
| Intravenous Abatacept | Double-blind Period: Maximum Observed Serum Concentration of Abatacept | 222.35 µg/mL | Standard Deviation 71.92 |
Secondary
Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169
The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered.
Time frame: Day 169
Population: All participants who received at least 1 dose of study medication at any time and had HAD-QI scores available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169 | 1.72 units on a scale | Standard Deviation 0.68 |
| Intravenous Abatacept | Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169 | 1.67 units on a scale | Standard Deviation 0.67 |
Secondary
Double-blind Period: Minimum Observed Serum Concentration of Abatacept
Time frame: Days 57, 85, 113, 120, 127, 134, 141, and 169
Population: Participants who received at least 1 dose of study medication and from whom at least 1 pharmacokinetic (PK) sample was collected and reported (N). Only participants with adequate PK profiles were included in the summary statistics and statistical analysis (n).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 85 (n=630, n=649) | 28.30 µg/mL | Standard Deviation 21.692 |
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 127 (n=28) | 29.16 µg/mL | Standard Deviation 14.78 |
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 57 (n=25, n=16) | 31.60 µg/mL | Standard Deviation 21.483 |
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 134 (n=27) | 25.10 µg/mL | Standard Deviation 15.753 |
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 141 (n=26, n=26) | 25.79 µg/mL | Standard Deviation 14.264 |
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 113 (n=44, n=29) | 26.49 µg/mL | Standard Deviation 16.569 |
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 169 (n=530, n=521) | 24.91 µg/mL | Standard Deviation 14.989 |
| Subcutaneous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 120 (n=27) | 25.10 µg/mL | Standard Deviation 14.933 |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 169 (n=530, n=521) | 18.10 µg/mL | Standard Deviation 17.94 |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 85 (n=630, n=649) | 20.00 µg/mL | Standard Deviation 13.441 |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 134 (n=27) | NA µg/mL | — |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 113 (n=44, n=29) | 18.76 µg/mL | Standard Deviation 16.322 |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 120 (n=27) | NA µg/mL | — |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 127 (n=28) | NA µg/mL | — |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 141 (n=26, n=26) | 18.10 µg/mL | Standard Deviation 17.717 |
| Intravenous Abatacept | Double-blind Period: Minimum Observed Serum Concentration of Abatacept | Day 57 (n=25, n=16) | 23.14 µg/mL | Standard Deviation 14.008 |
Secondary
Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169
The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% improvement from baseline 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 acute phase reactant value (C-reactive protein). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures.
Time frame: Day 169
Population: PP population, defined as participants who are compliant with the study criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169 | ACR 50 | 357 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169 | ACR 70 | 183 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169 | ACR 50 | 341 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169 | ACR 70 | 170 participants |
Secondary
Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169
The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ-DI response=an improvement of at least 0.3 units from baseline in HAQ-DI.
Time frame: Day 169
Population: All participants who received at least 1 dose of study medication at any time and had HAD-QI scores available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169 | 483 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169 | 442 participants |
Secondary
Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline
Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process.
Time frame: Baseline to Day 169
Population: All randomized participants who received at least 1 dose of study medication. n=Number of participants with at least 1 assessment available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF negative; Day 169 RF positive | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF negative | 106 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF positive | 586 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF positive ; Day 169 RF negative | 33 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF positive ; Day 169 RF negative | 40 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF positive | 582 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF negative | 93 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline | Baseline RF negative; Day 169 RF positive | 3 participants |
Secondary
Double-blind Period: Number of Participants With AEs of Special Interest
AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections,serious infections,and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (prespecified AEs occurring within 1 hr of start of infusion), peri-infusional AEs (prespecified AEs occurring within 24 hrs of the start of infusion), system injection reactions, and local injection site reactions
Time frame: Day 1 up to 56 days post last dose in short- term period or first dose in the long -term period, whichever occurs first.
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Malignancies | 3 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Acute Infusional AEs | 20 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Infections | 234 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Peri-infusional AEs | 59 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Autoimmune Disorders | 7 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Local Injection Site Reactions | 19 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Systemic Injection Reactions | 56 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Local Injection Site Reactions | 18 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Systemic Injection Reactions | 56 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Infections | 221 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Malignancies | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Autoimmune Disorders | 6 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Acute Infusional AEs | 16 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With AEs of Special Interest | Peri-infusional AEs | 59 participants |
Secondary
Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements
Vital sign measurements were performed for participants before and after infusion/subcutaneous injection of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.
Time frame: Day 1 through end of short-term period (Day 169)
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements | 0 participants |
Secondary
Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation
AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. 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 development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug
Time frame: Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Treatment-related SAEs | 5 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | AEs | 493 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | SAEs | 31 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Treatment-related AEs | 204 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | SAEs Leading to Discontinuation | 8 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | AEs Leading to Discontinuation | 15 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Deaths | 2 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | AEs Leading to Discontinuation | 25 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Deaths | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | SAEs | 35 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Treatment-related SAEs | 12 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | SAEs Leading to Discontinuation | 14 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | AEs | 470 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Treatment-related AEs | 210 participants |
Secondary
Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality
Marked abnormality criteria: Sodium: \<0.95\*LLN/\>1.05\*ULN, or if BL\<LLN, use \<0.95\* BL or \>ULN, or if BL\>ULN, use\>1.05\* BL or \<LLN; potassium: \<0.9\* LLN/\>1.1\*ULN, or if BL\<LLN then use \<0.9\* BL or \>ULN, or if BL\>ULN, use\>1.1\* BL or \<LLN; chlorine: \<0.9\*LLN/\>1.1\* ULN, or if BL\<LLN, use \<0.9\*BL or \>ULN, or if BL\>ULN, use\>1.1\*BL or \<LLN; calcium: \<0.8\* LLN/\>1.2\* ULN, or if BL\<LLN, use \<0.75\*BL or \>ULN, or if BL\>ULN, use\>1.25\* BL or \<LLN; phosphorous: \<0.75\* LLN/\>1.25\*ULN, or if BL\<LLN, use 0.67\*BL or \>ULN, or if BL\>ULN, use\>1.33\* BL or \<LLN
Time frame: Day 1 through end of short-term period (Day 169)
Population: All randomized participants who received at least 1 dose of study medication. N=number of participants with assessments available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low sodium (LLN=135 mEq/L) | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High potassium (ULN=5.5 mEq/L) | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High chlorine (ULN=109 mEq/L) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High calcium (ULN=10.6 mg/dL) | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High phosphorous (ULN=5.6 mg/dL) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High sodium (ULN=148 mEq/L) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low potassium (LLN=3.5 mEq/L) | 9 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low chlorine (LLN= 96 mEq/L) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low calcium (LLN=8.4 mg/dL) | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low phosphorous (LLN=0.8 mg/dL) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low calcium (LLN=8.4 mg/dL) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low potassium (LLN=3.5 mEq/L) | 9 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High potassium (ULN=5.5 mEq/L) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High calcium (ULN=10.6 mg/dL) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low chlorine (LLN= 96 mEq/L) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low phosphorous (LLN=0.8 mg/dL) | 2 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High chlorine (ULN=109 mEq/L) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low sodium (LLN=135 mEq/L) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High phosphorous (ULN=5.6 mg/dL) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality | High sodium (ULN=148 mEq/L) | 0 participants |
Secondary
Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality
ULN=upper limit of normal; LLN=lower limit of normal; BL= baseline. Marked abnormality criteria: Hemoglobin: \>3 g/dL decrease from BL; hematocrit: \<0.75\*BL; erythrocytes: \<0.75\*BL; platelets: \<0.67\*LLN/\>1.5\*ULN, or if BL\<LLN, use \<0.5\*BL and \<100,000 mm\^3; leukocytes: \<0.75\*LLN/\>1.25\*ULN, or if BL\<LLN use \<0.8\*BL or \>ULN, or if BL\>ULN, use \>1.2\*BL or \<LLN; neutrophils+bands: \<1.0\*10\^3 c/uL; eosinophils: \>0.750\*10\^3 c/uL; basophils: \>400 mm\^3; monocytes: \>2000 mm\^3; lymphocytes: \<0.750\*10\^3 c/uL/\>7.50\*10\^3 c/uL.
Time frame: Day 1 through end of short-term period (Day 169)
Population: All randomized participants who received at least 1 dose of study medication. n=Number of participants with assessments available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High platelets (ULN=450*10^9 c/L); n=725, 709 | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low hemoglobin (LLN=11.5 g/dL); n=729, 713 | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low leukocytes (LLN= 3.8*10^3 c/uL); n=729, 713 | 6 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low neutrophils+bands(LLN=1.8*10^3 c/uL);n=730,713 | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High leukocytes (ULN = 10.6*10^3 c/uL);n=729, 713 | 25 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low hematocrit (LLN=34%); n=726, 713 | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High eosinophils (ULN= 7*10^3 c/uL); n=730, 712 | 22 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High basophils (ULN= 0.2*10^3 c/uL); n=730, 712 | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High monocytes (ULN=1*10^3 c/uL); n=730, 712 | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low platelets (LLN=140*10^9 c/L); n=725, 709 | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low lymphocytes (LLN= 0.7*10^3 c/uL);n=730,712 | 40 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low erythrocytes(LLN=3.8 x10*6c/uL);n=729, 713 | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High lymphocytes(ULN=4.5*10^3 c/uL);n=730,712 | 40 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High lymphocytes(ULN=4.5*10^3 c/uL);n=730,712 | 42 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low neutrophils+bands(LLN=1.8*10^3 c/uL);n=730,713 | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High eosinophils (ULN= 7*10^3 c/uL); n=730, 712 | 16 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High basophils (ULN= 0.2*10^3 c/uL); n=730, 712 | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low hemoglobin (LLN=11.5 g/dL); n=729, 713 | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low hematocrit (LLN=34%); n=726, 713 | 4 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low platelets (LLN=140*10^9 c/L); n=725, 709 | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High platelets (ULN=450*10^9 c/L); n=725, 709 | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low leukocytes (LLN= 3.8*10^3 c/uL); n=729, 713 | 2 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High leukocytes (ULN = 10.6*10^3 c/uL);n=729, 713 | 18 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | High monocytes (ULN=1*10^3 c/uL); n=730, 712 | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low lymphocytes (LLN= 0.7*10^3 c/uL);n=730,712 | 42 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality | Low erythrocytes(LLN=3.8 x10*6c/uL);n=729, 713 | 3 participants |
Secondary
Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality
Marked abnormality criteria: Alkaline phosphatase (ALP): \>2\*ULN, or if BL\>ULN, use \>3\*BL; aspartate aminotransferase (AST): \>3\*ULN, or if BL\>ULN, use \>4\*BL; alanine aminotransferase (ALT): \>3\*ULN, or if BL\>ULN, use \>4\*BL; G-glutamyl transferase (GGT): \>2\* ULN, or if BL\>ULN, use \>3\*BL; bilirubin: \>2\* ULN, or if BL\>ULN, use \>4\*BL; blood urea nitrogen: \>2\* BL; creatinine: \>1.5\*BL
Time frame: Day 1 through end of short-term period (Day 169)
Population: All randomized participants who received at least 1 dose of study medication. n=Number of participants with assessments available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High ALT (ULN=55 U/L);n=729, 713 | 12 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High GGT (ULN=65 U/L); n=730, 713 | 8 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High ALP (ULN=400 U/L); n=730, 713 | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High bilirubin (ULN=1.2 mg/dL); n=730, 713 | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High AST (ULN=44 U/L); n=729, 713 | 5 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High creatinine (ULN=1.5 mg/dL); n=730, 713 | 19 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High blood urea nitrogen (26 mg/dL); n=730, 713 | 21 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High creatinine (ULN=1.5 mg/dL); n=730, 713 | 30 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High blood urea nitrogen (26 mg/dL); n=730, 713 | 27 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High AST (ULN=44 U/L); n=729, 713 | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High ALT (ULN=55 U/L);n=729, 713 | 16 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High GGT (ULN=65 U/L); n=730, 713 | 14 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High bilirubin (ULN=1.2 mg/dL); n=730, 713 | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality | High ALP (ULN=400 U/L); n=730, 713 | 3 participants |
Secondary
Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA)
Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept (anti-ABA) or anti-CTLA4 antibody (anti-CTLA4).
Time frame: Days 85, and 169 and postvisits on Days 28, 56, and 85
Population: All randomized participants who received at least 1 dose of study medication. n=Number of participants with at least 1 assessment available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 85 total (n=706, n=689) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 28 days post last dose total (n=20, n=27) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 85 days post last dose anti-CTLA4 (n=13, n=15) | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall post visits anti-CTLA4 (n=28, n=31) | 3 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall post visits total (n=28, n=31) | 3 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 85 anti-ABA (n=700, n=682) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 85 anti-CTLA4 (n=705, n=689 | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall on-treatment visits total (n=716, 702) | 5 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 169 anti-ABA (n=671, n=648) | 3 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 169 anti-CTLA4 (n=681, n=658) | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 169 total (n=681, n=658) | 5 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall on-treatment visits anti-ABA (n=707, 691) | 3 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall on-treatment visits anti-CTLA4 (n=716,702) | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 28 days post last dose anti-ABA (n=18, n=25) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 28 days post last dose anti-CTLA4 (n=20, n=27) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 56 days post last dose anti-ABA (n=19, n=22) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 56 days post last dose anti-CTLA4 (n=19, n=23) | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 56 days post last dose total (n=19, n=23) | 1 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 85 days post last dose anti-ABA (n=12, n=15) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 85 days post last dose total (n=13, n=15) | 2 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall post visits anti-ABA (n=26, n=29) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall anti-ABA (n=714, n=698) | 3 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall anti-CTLA4 (n=725, n=710) | 5 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall total (n=725, n=710) | 8 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall on-treatment visits total (n=716, 702) | 9 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 85 days post last dose anti-CTLA4 (n=13, n=15) | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 85 days post last dose anti-ABA (n=12, n=15) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 28 days post last dose anti-ABA (n=18, n=25) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall anti-ABA (n=714, n=698) | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall post visits anti-CTLA4 (n=28, n=31) | 7 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 28 days post last dose anti-CTLA4 (n=20, n=27) | 2 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall post visits total (n=28, n=31) | 7 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 28 days post last dose total (n=20, n=27) | 2 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 85 anti-ABA (n=700, n=682) | 2 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 85 days post last dose total (n=13, n=15) | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 85 anti-CTLA4 (n=705, n=689 | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 56 days post last dose anti-ABA (n=19, n=22) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 85 total (n=706, n=689) | 2 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall total (n=725, n=710) | 16 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 169 anti-ABA (n=671, n=648) | 4 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 56 days post last dose anti-CTLA4 (n=19, n=23) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 169 anti-CTLA4 (n=681, n=658) | 4 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall post visits anti-ABA (n=26, n=29) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Day 169 total (n=681, n=658) | 8 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | 56 days post last dose total (n=19, n=23) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall on-treatment visits anti-ABA (n=707, 691) | 5 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall anti-CTLA4 (n=725, n=710) | 11 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA) | Overall on-treatment visits anti-CTLA4 (n=716,702) | 4 participants |
Secondary
Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized
An electrochemiluminescence immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; abatacept molecule). Ig and/or Junction (JNCT) category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a postbaseline titer higher than Baseline, or any postbaseline positivity if Baseline value was missing. Trt=treatment.
Time frame: Days 85, and 169 and postvisits on Days 28, 56, and 85
Population: All participants who received at least 1 dose of abatacept and had at least 1 immunogenicity result reported during the short-term period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall post visits CTLA4+possibly Ig (n=3, n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall on-TRT Ig +/- JNCT (n=79, 70) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 169 CTLA4 + possibly Ig (n=75, n=67) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall on-TRT total (n=79, 70) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall post visits Ig +/- JNCT (n=3, n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 28 days post last dose CTLA4+possibly Ig (n=2,n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 28 days post last dose Total (n=2, n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 28 days post last dose Ig +/- JNCT (n=2, n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall CTLA4+possibly Ig (n=82, n=71) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 56 days post last dose CTLA4+possibly Ig (n=2,n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall Ig +/- JNCT (n=82, n=71) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 56 days post last dose Ig +/- JNCT (n=2, n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall total (n=82, n=71) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 56 days post last dose total (n=2, n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 85 CTLA4 + possibly Ig (n=78, n=67) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 85 total (n=78, n=67) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 85 Ig +/- JNCT (n=78, n=67) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 85 days post last dose total (n=1, n=1) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 85 days post last dose CTLA4+possibly Ig (n=1,n=1) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 169 Ig +/- JNCT (n=75, n=67) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall post visits total (n=3, n=2) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 85 days post last dose Ig +/- JNCT (n=1, n=1) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 169 total (n=75, n=67) | 0 participants |
| Subcutaneous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall on-TRT CTLA4 + possibly Ig (n=79, 70) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 28 days post last dose CTLA4+possibly Ig (n=2,n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 169 CTLA4 + possibly Ig (n=75, n=67) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 169 total (n=75, n=67) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 28 days post last dose Total (n=2, n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall post visits CTLA4+possibly Ig (n=3, n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall post visits total (n=3, n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 85 CTLA4 + possibly Ig (n=78, n=67) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 85 total (n=78, n=67) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 169 Ig +/- JNCT (n=75, n=67) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall on-TRT CTLA4 + possibly Ig (n=79, 70) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall on-TRT Ig +/- JNCT (n=79, 70) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall on-TRT total (n=79, 70) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Day 85 Ig +/- JNCT (n=78, n=67) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 28 days post last dose Ig +/- JNCT (n=2, n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 56 days post last dose CTLA4+possibly Ig (n=2,n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 56 days post last dose Ig +/- JNCT (n=2, n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 56 days post last dose total (n=2, n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 85 days post last dose CTLA4+possibly Ig (n=1,n=1) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 85 days post last dose Ig +/- JNCT (n=1, n=1) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | 85 days post last dose total (n=1, n=1) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall post visits Ig +/- JNCT (n=3, n=2) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall CTLA4+possibly Ig (n=82, n=71) | 1 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall Ig +/- JNCT (n=82, n=71) | 0 participants |
| Intravenous Abatacept | Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized | Overall total (n=82, n=71) | 1 participants |
Secondary
Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period
C-reactive protein is an acute phase reactant protein that is a clinical marker for rheumatoid arthritis. Time-matched median percent change from baseline= (time-matched baseline value - Post-baseline value)/time-matched baseline value\*100, where the time-matched baseline value represents the median baseline value for only that cohort of participants with measurements available at that visit.
Time frame: Baseline to Days 15, 29, 57, 85, 113, 141, and 169
Population: All randomized participants who received at least 1 dose of study medication. n=Number of participants with at least 1 assessment available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Subcutaneous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 169 (n=727, n=711) | 57.18 percent change |
| Subcutaneous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 15 (n=720, n=703) | 34.16 percent change |
| Subcutaneous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 29 (n=727, n=711) | 39.74 percent change |
| Subcutaneous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 57 (n=727, n=711) | 47.88 percent change |
| Subcutaneous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 113 (n=727, n=711) | 53.33 percent change |
| Subcutaneous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 141 (n=727, n=711) | 56.12 percent change |
| Subcutaneous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 85 (n=727, n=711) | 52.90 percent change |
| Intravenous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 113 (n=727, n=711) | 58.12 percent change |
| Intravenous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 141 (n=727, n=711) | 58.39 percent change |
| Intravenous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 169 (n=727, n=711) | 56.81 percent change |
| Intravenous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 57 (n=727, n=711) | 51.42 percent change |
| Intravenous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 15 (n=720, n=703) | 33.74 percent change |
| Intravenous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 85 (n=727, n=711) | 53.65 percent change |
| Intravenous Abatacept | Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period | Day 29 (n=727, n=711) | 42.52 percent change |
Secondary
Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821
The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from very good to very bad). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6. A clinically significant response= decrease in DAS28 score of \>1.2 from baseline.
Time frame: Days 169, 729, 1261, 1821
Population: All participants who entered the LT period and received at least 1 dose of study drug during the LT period were summarized.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821 | Day 169 (n=1353) | -2.65 units on a scale |
| Subcutaneous Abatacept | Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821 | Day 729 (n=1181) | -2.94 units on a scale |
| Subcutaneous Abatacept | Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821 | Day 1261 (n=1063) | -3.09 units on a scale |
| Subcutaneous Abatacept | Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821 | Day 1821 (n=413) | -3.24 units on a scale |
Secondary
Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline 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 acute phase reactant value (C-reactive protein).
Time frame: Days 169, 729, 1261, 1821
Population: All participants who entered the LT period and received at least 1 dose of study drug during the LT period were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821 | Day 1261 (n=1068) | 904 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821 | Day 1821 (n=421) | 356 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821 | Day 169 (n=1357) | 1087 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821 | Day 729 (n=1187) | 973 participants |
Secondary
Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821
The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% improvement from baseline 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 acute phase reactant value (C-reactive protein). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures.
Time frame: Days 169, 729, 1261, 1821
Population: All participants who entered the LT period and received at least 1 dose of study drug during the LT period were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 169 ACR 50 (n=1362) | 724 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 729 ACR 50 (n=1185) | 720 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 1261 ACR 50(n=1069) | 672 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 1821 ACR 50 (n=423) | 277 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 169 ACR 70 (n=1362) | 371 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 729 ACR 70 (n=1186) | 443 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 1261 ACR 70 (n=1070) | 438 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821 | Day 1821 ACR 70 (n=425) | 191 participants |
Secondary
Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821
The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from very good to very bad). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6.
Time frame: Days 169, 729, 1261, 1821
Population: All participants who entered the LT period and received at least 1 dose of study drug during the LT period were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821 | Day 169 (n=1355) | 553 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821 | Day 729 (n=1183) | 600 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821 | Day 1261 (n=1064) | 585 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821 | Day 1821 (n=413) | 238 participants |
Secondary
Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821
The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from very good to very bad). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6.
Time frame: Days 169, 729, 1261, 1821
Population: All participants who entered the LT period and received at least 1 dose of study drug during the LT period were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821 | Day 729 (n=1183) | 411 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821 | Day 1261 (n=1064) | 425 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821 | Day 169 (n=1355) | 334 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821 | Day 1821 (n=413) | 169 participants |
Secondary
Open-Label LT Period: Number of Participants With AEs of Special Interest
AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections, serious infections, and opportunistic infections; autoimmune disorders; malignancies; system injection reactions, and local injection site reactions.
Time frame: End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)
Population: All participants who entered the LT Period and received at least 1 dose of study drug during the LT Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | Serious Infections leading to Discontinuation | 16 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | Malignancies | 56 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | All Infections | 962 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | Serious Infections | 85 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | Infections leading to Discontinuation | 25 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | Autoimmune Disorders | 67 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | Local Injection Site Reactions | 33 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With AEs of Special Interest | Systemic Injection Reactions | 161 participants |
Secondary
Open-Label LT Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements
Vital sign assessments were performed in the LT period at 12-week intervals and at a yearly visit (at 16-week intervals) and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Vital signs included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.
Time frame: End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)
Population: All participants who entered the LT Period and received at least 1 dose of study drug during the LT Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements | 0 participants |
Secondary
Open-Label LT Period: Number of Participants With Clinically Significant Laboratory Abnormalities
Laboratory assessments were performed in the LT period at 12-week intervals and at a yearly visit and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Abnormalities were determined to be clinically significant by the investigator.
Time frame: End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)
Population: All participants who entered the LT Period and received at least 1 dose of study drug during the LT Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Clinically Significant Laboratory Abnormalities | 0 participants |
Secondary
Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation
AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. 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 development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug
Time frame: End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)
Population: All participants who entered the LT Period and received at least 1 dose of study drug during the LT Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | SAE | 353 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Death | 41 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Treatment-related SAE | 88 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | SAEs leading to Discontinuation | 73 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | Treatment-related AEs | 632 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation | AEs leading to Discontinuation | 97 participants |
Secondary
Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821
The disability section of the full HAQ includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI overall score ranges from a minimum of 0 to a maximum of 3.0. HAQ response was defined as an improvement (reduction) from baseline (Day 1) of at least 0.3 units in the HAQ score.
Time frame: Days 169, 729, 1261, 1821
Population: All participants who entered the LT period, received at least 1 dose of study drug during the LT period, and had HAD-QI scores at baseline and at specified days were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821 | Day 169 (n=1364) | 962 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821 | Day 729 (n=1190) | 853 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821 | Day 1261 (n=1068) | 780 participants |
| Subcutaneous Abatacept | Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821 | Day 1821 (n=427) | 315 participants |