A Rheumatoid Arthritis Study to Assess Early Response to Abatacept+MTX as Defined by Improvement of Synovitis Measures by Power Doppler Ultrasonography

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00767325
• Collaborator: (none)
• Enrollment: 104
• Locations: 21
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to assess early signs of response to abatacept+methotrexate in metacarpophalangeal joints in both hands using power Doppler ultrasonography in patients with active rheumatoid arthritis.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Abatacept; Drug: Methotrexate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Multi-Center, Open Label Study to Assess Early Response to Abatacept With Background Methotrexate Using Power Doppler Ultrasonography in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abatacept, 10 mg/kg	Drug: Abatacept; Abatacept, 10 mg/kg, solution given intravenously on Days 1, 15, 29,57, 85, 113, 141, and 169; Other Names: Orencia® BMS-188667 ; Drug: Methotrexate; Methotrexate administered in a dose of 15 mg/week or higher for at least 3 months and at a stable dose for at least 28 days prior to baseline

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) [Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169]

   LOCF=last observation carried forward. PDUS assessed the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. Total PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and Grade 2 Doppler signal; Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤Grade 3 Doppler signal or minimal or moderate synovial hypertrophy and Grade 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for 2 hands. Higher grade/score=more severe disease. Change=score Day x - baseline score.

2. Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed [Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169]

   MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography. Time point at which early signs of Global PDUS improvement were observed=earliest time point for which 0 was not included in the 95% confidence interval for the mean changes from baseline in Global PDUS (MCP 2-5) score at that and all later time points. Total PDUS scores are independent of the presence and grade of joint effusion: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH, with ≤Gr 2 Doppler signal or minimal SH and grade 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher Gr/score=more severe disease.

Secondary Outcome Measures

1. Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) [Days 7, 15, 29, and 169]

   PDUS=power Doppler ultrasonography; MCP=metacarpophalangeal; LOCF=last observation carried forward. PDUS was used to assess the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and grade 2 Doppler signal); Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤ Grade 3 Doppler signal or minimal or 1-3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher grade/score=more severe disease. Change=score Day X-baseline score.

2. Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP [Days 1 to 169]

   MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography; DAS=Disease Activity Score;CRP=C-reactive protein. Receiver Operator Characteristics (ROC) analysis assessed predicatability. ROC curve analyses performed; area under the curve of ≥0.7 was considered acceptable for prediction. Clinical response defined as: Clinically Meaningful Improvement=drop from baseline of ≥1.2 in DAS28-CRP; Remission=DAS28-CRP score <2.6; Low Disease Activity=≤3.2. PDUS scores: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH with ≤Gr 2 Doppler signal or minimal SH and Gr 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint rated 1-3, for a total possible score ranging from 8-24 (8*1, 8*3)for the 2 hands. Higher gr/score=more severe disease.

3. Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs [Days 1 to 169 to 56 days following last infusion]

   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. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

4. Number of Participants With Adverse Events (AEs) of Interest [Days 1 to 169 to 56 days following last infusion]

   AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Infusion reaction: acute=1 hour or less after start of dosing; periinfusional=24 hours or less after start of dosing.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key inclusion riteria:

• Disease activity defined by a disease activity score 28-C-reactive protein >3.2, or meeting the following criteria: a tender joint count ≥6; a swollen joint count ≥6; C-reactive protein measurement greater than the upper limit of normal

• Diagnosis of rheumatoid arthritis for longer than 6 months from time of initial diagnosis

• Total synovitis power Doppler ultrasonography (PDUS) score >1 for at least 2 metacarpophalangeal (MCP) joints (MCP2-5) and a total synovitis PDUS score ≥1 for at least 1 other MCP joint (MCP2-5)

• Concomitant treatment with methotrexate at a dose ≥15 mg for at least 3 months before Day 1 and a stable dose for the last 28 days before Day 1

• No treatment with any background nonbiologic disease-modifying antirheumatic drug (DMARD) other than methotrexate for at least 28 days before treatment (Day 1)

• Stable dose of corticosteroids equivalent of 10 mg prednisone /day during the 28 days prior to Day 1

• Naive to treatment with biologic DMARDs

Key exclusion criteria:

• Women of childbearing potential who are unwilling or unable to use birth control

• Women who are pregnant or breastfeeding

• Meeting all diagnostic criteria for any other rheumatic disease

• Previous MCP arthroplasty, with such a procedure scheduled, or anticipating the need for such a procedure during the study. Participants who had undergone or were scheduled to undergo joint arthroplasties other than of the MCP joints were permitted to enroll in the study provided all other eligibility criteria were met.

• Active vasculitis of a major organ system with the exception of rheumatoid nodule

• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not related to rheumatoid arthritis

• History of cancer in the last 5 years, other than nonmelanoma skin cell cancer cured by local resection or carcinoma in situ. Existing nonmelanoma skin cell cancers should have been removed, the lesion site healed, and residual cancer ruled out prior to administration of study medication

• Clinically significant abuse of alcohol or drugs

• Evidence of active or latent bacterial or viral infections at the time of potential enrollment

• Herpes zoster or cytomegalovirus infection that resolved less than 2 months before the informed consent document was signed

• For participants at risk for tuberculosis (TB):

• A history of active (TB) within the last 3 years, even if treated

• Latent TB that was not successfully treated ≥4 weeks

• Current clinical, radiographic, or laboratory evidence of active TB.

• Participants who have received live vaccines within 3 months of the anticipated first dose of study medication

• Participants with positive test results for hepatitis B surface antigen or hepatitis C antibody, with hepatitis C virus detected with polymerase chain reaction or recombinant immunoblot assay.

• Participants with hemoglobin level <8.5 g/dL or white blood cell count< 3000/mm^{3 or platelet count <100,000/mm}3 or serum creatinin level >2the upper limit of normal (ULN) or serum alanine transaminase level or aspartate aminotransferase level >2ULN

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Glostrup		Denmark	DK-2600
2	Local Institution	Bois Guillaume Cedex		France	76230
3	Local Institution	Boulogne		France	92104
4	Local Institution	Echirolles		France	38434
5	Local Institution	Nice Cedex 03		France	06202
6	Local Institution	Munchen		Germany	80639
7	Local Institution	Budapest		Hungary	1036
8	Local Institution	Jesi (Ancona)		Italy	60035
9	Local Institution	Pisa		Italy	56126
10	Local Institution	Roma		Italy	00161
11	Local Institution	Roma		Italy	00168
12	Local Institution	Siena		Italy	53100
13	Local Institution	Verona		Italy	37126
14	Local Institution	Oslo		Norway	N0319
15	Local Institution	Trondheim		Norway	7006
16	Local Institution	Barcelona		Spain	08006
17	Local Institution	Madrid		Spain	28006
18	Local Institution	Madrid		Spain	28040
19	Local Institution	Madrid		Spain	28911
20	Local Institution	Madrid		Spain	28935
21	Local Institution	Leeds	North Yorkshire	United Kingdom	LS7 4SA

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00767325
• Other Study ID Numbers: IM101-179
• First Posted: Oct 7, 2008
• Last Update Posted: Jul 2, 2013
• Last Verified: Jun 1, 2013

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Methotrexate; Abatacept

Study Results

Participant Flow

Pre-assignment Detail	A total of 164 participants were screened; 104 were enrolled in the study and received open-label treatment with abatacept.

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Period Title: Overall Study
STARTED	104
COMPLETED	89
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Overall Participants	104
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.4 (14.1)
Sex: Female, Male (Count of Participants)
Female	87 83.7%
Male	17 16.3%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	1 1%
Asian	1 1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	101 97.1%
Other	1 1%
Tender joint count (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	19.5 (12.5)
Duration of rheumatoid arthritis (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	7.3 (9.1)
Swollen joint count (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	13.0 (7.6)
DAS 28-CRP score (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	5.2888 (1.105)
Global PDUS (MCP 2-5) score (n=96) (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	12.6 (4.1)

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis)
Description	LOCF=last observation carried forward. PDUS assessed the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. Total PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and Grade 2 Doppler signal; Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤Grade 3 Doppler signal or minimal or moderate synovial hypertrophy and Grade 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for 2 hands. Higher grade/score=more severe disease. Change=score Day x - baseline score.
Time Frame	Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Measure Participants	96
Day 7 (n=86)	-0.7 (0.282)
Day 15 (n=94)	-1.3 (0.308)
Day 29 (n=95)	-2.4 (0.383)
Day 43 (n=95)	-2.9 (0.384)
Day 57 (n=95)	-3.2 (0.393)
Day 85 (n=95)	-3.8 (0.454)
Day 113 (n=95)	-4.5 (0.472)
Day 141 (n=95)	-4.8 (0.492)
Day 169 (n=95)	-4.8 (0.473)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.282
	Estimation Comments	Day 7

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.0 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.308
	Estimation Comments	Day 15

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -3.2 to -1.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.383
	Estimation Comments	Day 29

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -3.7 to -2.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.384
	Estimation Comments	Day 43

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -4.0 to -2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.393
	Estimation Comments	Day 57

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95%; -4.7 to -2.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.454
	Estimation Comments	Day 85

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -5.4 to -3.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.472
	Estimation Comments	Day 113

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -5.8 to -3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.492
	Estimation Comments	Day 141

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 10 mg/kg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -5.8 to -3.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.473
	Estimation Comments	Day 169

2. Secondary Outcome

Title	Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis)
Description	PDUS=power Doppler ultrasonography; MCP=metacarpophalangeal; LOCF=last observation carried forward. PDUS was used to assess the degree of synovial inflammation of the MCP joints (2nd to 5th) of both hands and was performed at approximately the same time of day for each participant. PDUS scores are independent of the presence and grade of joint effusion and are evaluated as follows: Grade 0 or normal=normal joint (no synovial hypertrophy, no Doppler signal); Grade 1 or minimal=minimal synovitis (minimal synovial hypertrophy, with ≤Grade 1 Doppler signal); Grade 2 or moderate=moderate synovitis (moderate synovial hypertrophy with ≤Grade 2 Doppler signal or minimal synovial hypertrophy and grade 2 Doppler signal); Grade 3 or severe=severe synovitis (severe synovial hypertrophy with ≤ Grade 3 Doppler signal or minimal or 1-3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher grade/score=more severe disease. Change=score Day X-baseline score.
Time Frame	Days 7, 15, 29, and 169

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Measure Participants	96
Synovial hypertrophy (n=86): Day 7	-0.6 (0.297)
Synovial hypertrophy (n=94): Day 15	-1.0 (0.306)
Synovial hypertrophy (n=95): Day 29	-2.1 (0.377)
Synovial hypertrophy (n=95): Day 169	-4.5 (0.449)
Doppler signal: Day 7 (n=86)	-0.9 (0.305)
Doppler signal: Day 15 (n=94)	-1.9 (0.296)
Doppler signal: Day 29 (n=95)	-2.2 (0.350)
Doppler signal: Day 169 (n=95)	-4.8 (0.457)
Joint effusion: Day 7 (n=86)	0.1 (0.237)
Joint effusion: Day 15 (n=94)	0.1 (0.243)
Joint effusion: Day 29 (n=95)	-0.8 (0.294)
Joint effusion: Day 169 (n=95)	-1.9 (0.351)

3. Primary Outcome

Title	Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed
Description	MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography. Time point at which early signs of Global PDUS improvement were observed=earliest time point for which 0 was not included in the 95% confidence interval for the mean changes from baseline in Global PDUS (MCP 2-5) score at that and all later time points. Total PDUS scores are independent of the presence and grade of joint effusion: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH, with ≤Gr 2 Doppler signal or minimal SH and grade 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint is rated 1 to 3, for a total possible score ranging from 8 to 24 (8*1, 8*3) for the 2 hands. Higher Gr/score=more severe disease.
Time Frame	Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Measure Participants	96
Number [Day]	7

4. Secondary Outcome

Title	Number of Early (Days 7 to 113) Global PDUS MCP 2-5 Scores or Global PDUS Component MCP 2-5 Scores Associated With an Acceptable Predictability of Clinical Response at Day 169, As Assessed by DAS28-CRP
Description	MCP=metacarpophalangeal; PDUS=power Doppler ultrasonography; DAS=Disease Activity Score;CRP=C-reactive protein. Receiver Operator Characteristics (ROC) analysis assessed predicatability. ROC curve analyses performed; area under the curve of ≥0.7 was considered acceptable for prediction. Clinical response defined as: Clinically Meaningful Improvement=drop from baseline of ≥1.2 in DAS28-CRP; Remission=DAS28-CRP score <2.6; Low Disease Activity=≤3.2. PDUS scores: Grade (Gr) 0 or normal=normal joint (no synovial hypertrophy [SH], no Doppler signal); Gr 1 or minimal=minimal synovitis (minimal SH, with ≤Gr 1 Doppler signal); Gr 2 or moderate=moderate synovitis (moderate SH with ≤Gr 2 Doppler signal or minimal SH and Gr 2 Doppler signal); Gr 3 or severe=severe synovitis (severe SH with ≤Gr 3 Doppler signal or minimal or moderate SH and Gr 3 Doppler signal). Each joint rated 1-3, for a total possible score ranging from 8-24 (8*1, 8*3)for the 2 hands. Higher gr/score=more severe disease.
Time Frame	Days 1 to 169

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 infusion of study drug and who had baseline and at least 1 postbaseline efficacy measurements available. Excludes 8 participants with PDUS values from 1 site that experienced technical and quality issues with PDUS scoring and compliance.

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Measure Participants	96
Clinically meaningful improvement	0
Remission	0
Low disease activity	0

5. Secondary Outcome

Title	Number of Participants With Death as Outcome, Serious Adverse Events(SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, Discontinuations Due to AEs
Description	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. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Time Frame	Days 1 to 169 to 56 days following last infusion

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 infusion of study drug.

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Measure Participants	104
Deaths	0 0%
SAEs	6 5.8%
Treatment-related SAEs	2 1.9%
Discontinuations due to SAEs	1 1%
AEs	62 59.6%
Treatment-related AEs	22 21.2%
Discontinuations due to AEs	6 5.8%

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) of Interest
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Infusion reaction: acute=1 hour or less after start of dosing; periinfusional=24 hours or less after start of dosing.
Time Frame	Days 1 to 169 to 56 days following last infusion

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 infusion of study drug.

Arm/Group Title	Abatacept, 10 mg/kg
Arm/Group Description	All participants received abatacept by intravenous infusion at a fixed-dose approximating 10 mg/kg on Days 1, 15, 29, 57, 85, 113, 141, and 169 in addition to oral methotrexate. Abatacept dose was based on body weight at screening.
Measure Participants	104
Infections	20 19.2%
Malignancy	1 1%
Autoimmune disorders (prespecified)	2 1.9%
Infusion reactions (prespecified): Acute	4 3.8%
Infusion reactions (prespecified): Periinfusional	10 9.6%

Adverse Events

Arm/Group Title	Aba 10 mg/kg
Arm/Group Description
All Cause Mortality
	Aba 10 mg/kg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aba 10 mg/kg
	Affected / at Risk (%)	# Events
Total	6/104 (5.8%)
Cardiac disorders
Atrial fibrillation	1/104 (1%)
Infections and infestations
Bursitis infective	1/104 (1%)
Nervous system disorders
Dementia	1/104 (1%)
Reproductive system and breast disorders
Endometriosis	1/104 (1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary fistula	1/104 (1%)
Pleural effusion	1/104 (1%)
Vascular disorders
Hypertension	1/104 (1%)
Other (Not Including Serious) Adverse Events
	Aba 10 mg/kg
	Affected / at Risk (%)	# Events
Total	15/104 (14.4%)
Infections and infestations
Nasopharyngitis	7/104 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	9/104 (8.7%)

Limitations/Caveats

Power Doppler ultrasonography values from 1 site (8 participants were excluded due to technical and quality issues with PDUS scoring and compliance issues.)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.