Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3*3 wrist regions), indicating most severe damage. Change in synovitis = Follow-up synovitis score - baseline score.

All randomized participants who received at least 1 dose of study medication and had synovitis assessments available at baseline.

Bone erosion assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 (no damage) to 10 (severe damage) according to erosion of the original articular bone (each unit=10% loss of articular bone). The total erosion score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 230. Increasing score=greater severity.

All randomized participants who received at least 1 dose of study medication and had erosion OMERACT 6 assessments available at baseline.

Bone erosion assessed at 23 anatomic locations: 15 in 1 wrist and 8 in attached hand. Each site is scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. Total erosion score for hands/wrists is sum of the individual scores for each location. Thus the maximum score per hand/wrist is 230. Increasing score=greater severity. Adjusted change from baseline in erosion score=mean score at Day 113-mean erosion score at baseline. Adjustment based on ANCOVA model with treatment=factor and baseline value=covariate.

All randomized participants who received at least 1 dose of study medication and had erosion OMERACT 6 assessments available at baseline and Day 113.

Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3*3 wrist regions), indicating most severe damage. Change in synovitis=Follow-up synovitis score-baseline score.

All randomized participants who received at least 1 dose of study medication and had wrist synovitis assessments available at baseline and Day 113.

Osteitis assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 to 3, indicating involvement of original articular bone. The total score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 23 (total number of anatomic locations) * 3 (maximum per joint)=69. Minimum score=0, indicating normal. Increasing score=greater severity.

All randomized participants who received at least 1 dose of study medication and had osteitis OMERACT 6 assessments available at baseline.

Osteitis assessed at 23 anatomic locations: 15 in 1 wrist and 8 in attached. Each site scored in 1.0 increments, indicating involvement of original articular bone (0=none to 3=severe). Total score for hands/wrists is sum of scores for each location. Maximum score per hand/wrist is 23 (total anatomic locations)*3 (maximum score per joint)=69. Minimum score=0(normal). Increasing score=greater severity. Adjusted mean change from baseline in osteitis score=mean score at Day 113-mean score at baseline. Adjustment based on ANCOVA model with treatment=factor and baseline value=covariate.

All randomized participants who received at least 1 dose of study medication and had osteitis OMERACT 6 assessments available at baseline and Day 113.

Bone erosion and osteitis were assessed at a total of 23 anatomic locations according to erosion (for bone erosion) or involvement (for osteitis) of the original articular bone. Synovitis assessed as above-normal post-gadolinium enhancement in 3 wrist regions: distal radioulnar joint, radiocarpal joint, and intercarpal and carpometacarpal joints.

All randomized participants who received at least 1 dose of study medication and had erosion, edema, and synovitis assessments available at baseline and Day 113.

RAMRIS score is the sum of its core components: Synovitis Score, Osteitis Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Osteitis scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score + Osteitis Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Osteitis Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.

All randomized participants who received at least 1 dose of study medication and had RAMRIS assessments available at baseline.

RAMRIS Score=sum of core components: Synovitis (S), Osteitis (O), and Erosion (E) Scores. S scored 0 (none) to 9 (maximum distension of synovial cavity); O scored 0 (none) to 69 (maximum articular bone involvement); E scored 0 (none) to 230 (maximum erosion of articular bone). RAMRIS=S+O+E Scores. RAMRIS minimum score=0 (normal), maximum=308 (severe structural damage). Adjusted change from baseline in RAMRIS=mean RAMRIS at Day 113-mean RAMRIS at baseline. Adjustment based on ANCOVA model: treatment=factor, baseline value=covariate.

All randomized participants who received at least 1 dose of study medication and had RAMRIS assessments available at baseline and Day 113.

PINP and osteocalcin are markers of bone formation. Osteocalcin is synthesized by osteoblasts and is associated with osteoblast synthetic activity. Osteoblasts secrete type 1 procollagen, and cleavage of large fragments from the carboxy and amino terminal ends result in formation of mature type 1 collagen and production of PINP fragments.

All randomized participants who received at least 1 dose of study medication.

CTX-I and ICTP are biochemical markers of bone resorption or bone degradation

All randomized participants who received at least 1 dose of study medication.

Urinary CTX-II is a biochemical marker of type II collagen breakdown. In participants with early rheumatoid arthritis, increased levels of CTX-II can be predictive of rapid radiographic progression over periods of 1 to 5 years. These markers of cartilage destruction can predict progression of joint damage, independent of clinical and biologic indices of disease activity and baseline joint damage.

All randomized participants who received at least 1 dose of study medication.

Glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) is a specific biochemical marker reflecting the degradation of the synovial tissue membrane. It is a glycosylated derivative of the collagen crosslink pyridinoline, and it is present in significant amounts only in the synovial membrane; it is absent from bone and present in minutes amounts in cartilage and other soft tissues. Increased urinary levels of Glc-Gal-PYD have been found in early and long-standing rheumatoid arthritis, high levels being associated with rapid destruction.

All randomized participants who received at least 1 dose of study medication.

An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.

All randomized participants who received at least 1 dose of study medication.

An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including serious, opportunistic, and all other infections; autoimmune disorders; neoplasms; acute infusional AEs (prespecified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (prespecified AEs occurring within 24 hours of start of infusion).

All randomized participants who received at least 1 dose of study medication.

Infections/Infestations of Special Interest are AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment.

All randomized participants who received at least 1 dose of study medication.

Acute infusional AEs are AEs with onset during the first hour after the start of study drug infusion. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs considered possibly, probably, or certainly related to study treatment were graded according to Common Terminology Criteria for Adverse Events ,Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).

All randomized participants who received at least 1 dose of study medication.

Peri-infusional AEs are AEs occurring during the first 24 hours after the start of study drug infusion. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs considered possibly, probably, or certainly related to study treatment were graded according to Common Terminology Criteria for Adverse Events, Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).

All randomized participants who received at least 1 dose of study medication.

BL=baseline; LLN=lower limit of normal; ULN=upper limit of normal. 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/<100,000 mm^3. Leukocytes: <0.75*LLN/>1.25*ULN, or if BL<LLN, use <0.8*BL/>ULN, or if BL>ULN, use >1.2*BL/<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.

All randomized participants who received at least 1 dose of study medication.

ULN=upper limit of normal; BL=baseline. Marked abnormality criteria: Alkaline phosphatase: >2*ULN, or if BL>ULN, use >3*BL; aspartate aminotransferase: >3*ULN, or if BL>ULN,use >4*BL; alanine aminotransferase: >3*ULN, or if BL>ULN, use >4*BL; G-Glutamyl transferase: >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.

All randomized participants who received at least 1 dose of study medication.

LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Marked abnormality: 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, use 0.9*BL or >ULN, or if BL>ULN, use>1.1*BL or <LLN. Chloride: <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 \

All randomized participants who received at least 1 dose of study medication.

LLN=lower limit of normal; ULN=upper limit of normal; BL-baseline. Marked abnormality c: serum glucose:<65 mg/dL/>220 mg/dL; fasting serum glucose: <0.8* LLN/>1.5* ULN, or if BL<LLN, use 0.8*BL or >ULN, or if BL>ULN, use >2.0*BL or <LLN; total protein: <0.9*LLN/>1.1* ULN; albumin: <0.9*LLN,or if BL<LLN, use <0.75 BL; uric acid: >1.5* ULN, or if BL>ULN, use >2*BL. Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, red blood cells, white blood cells):Use ≥2 when BL value missing or value ≥4,or when predose=0 or 0.5. Use ≥3 when predose=1. Use ≥4 when predose=2 or 3

All randomized participants who received at least 1 dose of study medication.

Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3*3 wrist regions), indicating most severe damage. Change in synovitis score=Follow-up synovitis score-baseline synovitis score.

All randomized participants who received at least 1 dose of study medication and who had wrist synovitis assessments available at baseline and Day 113.

Vital signs, which included blood pressure, heart rate, respiration, and temperature, were monitored predose and 1 hour after start of infusion. Changes in vital signs were determined to be significantly abnormal at the discretion of the investigator but were generally those that either exceeded, or failed to reach, normal parameters. Normal vital sign parameter ranges varied by site.

All randomized participants who received at least 1 dose of study medication.

On-Rx=on treatment; post-Rx=post treatment. ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1.

All randomized participants who received at least 1 dose of study medication.