Study to Assess Steady-State Trough Concentrations, Safety, and Immunogenicity of Abatacept After Subcutaneous (SC) Administration to Subjects With Rheumatoid Arthritis (RA)

Short Term Period: Peak Serum Concentration (Cmax) of Abatacept at Steady State in Participants With Rheumatoid Arthritis Receiving DMARDS

Peak serum concentration (Cmax) of abatacept after weekly SC administration was determined between the SC dosing interval from Day 71 to 78. Abatacept in human serum was measured by enzyme-linked immunosorbent assay (ELISA). Lower limit of quantification (LLOQ) was 0.001, Upper limit of quantification (ULOQ) was 0.030. Cmax measured in micrograms per milliliter(µg/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 71 to Day 78

Short Term Period: Area Under the Curve (AUC) in Time Interval of 7 Days [AUC(TAU)] of Abatacept in Participants With Rheumatoid Arthritis Receiving DMARDS

The steady-state pharmacokinetic parameter AUC(TAU) of abatacept after weekly SC administration was determined between the SC dosing interval from Day 71 to 78 (TAU=7 days). Abatacept in human serum was measured by enzyme-linked immunosorbent assay (ELISA). Lower limit of quantification (LLOQ) was 0.001; Upper limit of quantification (ULOQ) was 0.030. AUC(TAU) measured in in micrograms\*hours per milliliter (µg\*h/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 71 to Day 78

Short Term Period: Summary of Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs During 12 Weeks of Treatment With Either Abatacept or Placebo

Number of Participants with Adverse events (AEs), Serious AEs, discontinuations due to AEs, or Deaths occurring while participant was on treatment from Day 1 (treatment) to Day 85 or early termination from the study. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (also included hospitalizations for elective surgical procedures). Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 1 to Day 85 (or early termination)

Short Term Period: Number of Participants With Pre-specified Adverse Events (AEs) of Special Interest After Administration of Abatacept or Placebo Over 12 Weeks

AEs of special interest: infection and/or infestation; neoplasms (benign, malignant, unspecified; autoimmune disorder; infusional AEs (peri-infusional: AEs occurring during first 24 hours (hrs) after start of the IV loading dose; acute infusional: AEs occurring during the first hour after the start of the IV loading dose; injection site AEs: AEs occurring at the site of the SC injection. Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 1 to Day 85 (or early termination)

Short Term Period: Mean Percent Change From Baseline on Day 85 in Participants Positive for Serum Rheumatoid Factor During Abatacept or Placebo Administration

Serum samples were obtained on Days 1, 8, 15, 29, 57 and day of discharge (Day 85 or earlier) for determination of presence of rheumatoid factor (RF). Baseline was defined as Day 1 to calculate percent change. Lower limit of quantitation (LLQ) was 5 Units/milliliter (U/mL). Values below LLQ were set to 2.5 U/mL. Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 1 to Day 85 (or early termination)

Short Term Period: Number of Participants With Laboratory Abnormalities in Hematology at Baseline (Day 1) to End of Period (Day 85)

Blood samples were obtained: At screening, within 24 hours prior to study drug administration on Day 1, on Days 15, 29, 57 and at study discharge. Baseline (BL) defined as Day 1 prior to treatment. Common toxicity criteria (CTC), Version 3 used to assess parameters. lower limit of normal (LLN). ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:\<LLN to 3.0\*10\^9/L, Gr 2:\<3.0 to 2.0\*10\^9/L, Gr 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L. ANC Gr 1:\<LLN to 1.5\*10\^9/L, Gr 2:\<1.5 to 1.0\*10\^9/L, Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Lymphocytes Gr 1: \<LLN to 3.0, Gr 2: 2.0 \< 3.0, Gr 3: 1.0 to \< 2.0, Gr 4; \< 1.0. Platelet count Gr 1:LLN to 75.0\*10\^9/L, Gr 2:\<75.0 to 50.0\*10\^9/L, Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Hemoglobin Gr 1:\<LLN to 10.0 g/dL, Gr 2:\<10.0 to 8.0 g/dL, Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Hematocrit (%): \<0.75\*pre-treatment. Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 1 to Day 85 (or early termination)

Short Term Period: Number of Participants With Laboratory Abnormalities in Serum Chemistry at Baseline and on Treatment up to Day 85

Screening, BL, Days 15, 29, 57, 85 or discharge. Upper limit of normal (ULN). CTC grade (Gr): Alanine transaminase Gr 1:\>ULN to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Aspartate aminotransferase Gr 1: \>ULN to 2.5\*ULN; Gr 2:\>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. G-Glutamyl Transferase (U/L) Gr 1:\>ULN to 2.5\*ULN; Gr 2: \>2.5 to 5.0\*ULN; Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Alkaline phosphatase (U/L) Gr 1:\>ULN to 2.5\*ULN, Gr2:\>2.5 to 5.0\*ULN, Gr3:\>5.0 to 20.0\*ULN, Gr4: \>20.0\*ULN; creatinine (mg/dL) Gr 1: \>ULN to 1.5\*ULN; Gr 2: \>1.5 to 3.0\*ULN; Gr 3: \>3.0 to 6.0\*ULN; Gr 4: \>10.0\*ULN. Albumin (g/dL) Gr 1:\<LLN to 3.0; Gr 2:\<3.0 to 2.0; Gr 3: \<2.0. Uric Acid (mg/dL)Gr 1: \>1.0 x ULN to 10.0; Gr 4: \>10.0. Sodium (mEq/L) Gr 1: \>ULN to 150; Gr 2: \>150 to 155; Gr 3: \>155 to 160; Gr 4: \> 160. Potassium (mEq/L) Gr 1: \>ULN to 5.5; Gr 2: \>5.5 to 6.0; Gr 3: \>6.0 to 7.0; Gr 4: \>7.0. Data presented by treatment participant actually received.

Time frame: Day 1 to Day 85 (or early termination)

Short Term Period: Mean Change From Baseline at Day 85 in Blood Pressure After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS

Blood pressure (systolic and diastolic) was recorded while the participant was seated during the screening visit, at baseline on Day 1 (prior to administration of IV infusion), prior to administration of all SC injections, and at study discharge (Day 85 or 7 days after the last dose for subjects who terminated early). In addition, blood pressure was recorded at 30 and 60 minutes after the start of the IV infusion on Day 1, and 30 and 60 minutes after all SC injections. Blood pressure was measured in millimeters of mercury (mm Hg). Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 1 to Day 85 (or early termination)

Short Term Period: Mean Change From Baseline at Day 85 in Pulse Rate After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS

Pulse rate was taken while participant was seated. Pulse rate was recorded during the screening visit, at baseline on Day 1 (prior to administration of IV infusion), prior to administration of all SC injections, and at study discharge (Day 85 or 7 days after the last dose for subjects who terminated early). In addition, vital signs were recorded at 30 and 60 minutes after the start of the IV infusion on Day 1, and 30 and 60 minutes after all SC injections. Pulse rate measured in beats/min (bpm). Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Day 1 to Day 85 (or early termination)

Short Term Period: Mean Change From Screening to Day 85 in Electrocardiogram (QT, PR Intervals, QRS Width) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS

A 12-lead electrocardiogram (ECG) was recorded at screening and at discharge from the study (Day 85 or 7 days after the last dose of study drug for those subjects who terminated early). If there was no history of known cardiac events, an ECG was performed within 6 months of study entry, and documentation was on file, then the screening ECG was not repeated at screening. QT interval, PR interval and QRW Width were reported in milliseconds (msec). If no ECG issues were found in the 12 weeks of the Short Term Period, ECG was not repeated during LTE. Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Screening to Day 85 (or early termination)

Short Term Period: Mean Change From Screening at Day 85 in ECG (Heart Rate) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS

A 12-lead electrocardiogram (ECG) was recorded at screening and at discharge from the study (Day 85 or 7 days after the last dose of study drug for those subjects who terminated early). If there was no history of known cardiac events, an ECG was performed within 6 months of study entry, and documentation was on file, then the screening ECG was not repeated at screening. Heart Rate was reported in beats per minute (bpm). In no ECG issues were found in the 12 weeks of the Short Term Period, ECG was not repeated during LTE. Data are presented by treatment the participant actually received, not by what they were randomized to receive.

Time frame: Screening to Day 85 (or early termination)

Overall Study ST and LTE Periods: Number of Participants With Anti-abatacept Antibodies and/or Anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibodies

Assessment of positive antibody response based upon analysis using a validated enzyme-linked immunosorbent assay (ELISA) with a cut-off value. CTLA4 is a protein receptor that downregulates the immune system. Short Term (ST) period was initial 12 Weeks of the study. Overall LTE includes both the variable and fixed abatacept dosing periods and was from the end of the ST period (Day 85) up to 168 days post last dose (treatment in LTE ranged from 4.4 to 74.2 months. Data in the ST period are summarized by the treatment the participants actually received, while the LT period data are summarized by treatment the participant was randomized to receive.

Time frame: ST: Day 1 to Day 85; LTE: Day 85 to 168 days post last dose