Trial Outcomes & Findings for A Rheumatoid Arthritis Study to Assess Early Response to Abatacept+MTX as Defined by Improvement of Synovitis Measures by Power Doppler Ultrasonography (NCT NCT00767325)

Last Updated: 2013-07-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

104 participants

Primary outcome timeframe

Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169

Results posted on

2013-07-02

Participant Flow

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

Participant milestones

Participant milestones
Measure	Abatacept, 10 mg/kg 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 Study STARTED	104
Overall Study COMPLETED	89
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Abatacept, 10 mg/kg 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 Study Lack of Efficacy	2
Overall Study Adverse Event	7
Overall Study Lost to Follow-up	3
Overall Study No longer met study criteria	2
Overall Study Missed visit due to family reasons	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abatacept, 10 mg/kg n=104 Participants 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.
Age Continuous	56.4 Years STANDARD_DEVIATION 14.1 • n=5 Participants
Sex: Female, Male Female	87 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants
Race/Ethnicity, Customized White	101 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Tender joint count	19.5 Joints STANDARD_DEVIATION 12.5 • n=5 Participants
Duration of rheumatoid arthritis	7.3 Years STANDARD_DEVIATION 9.1 • n=5 Participants
Swollen joint count	13.0 Joints STANDARD_DEVIATION 7.6 • n=5 Participants
DAS 28-CRP score	5.2888 Units on a scale STANDARD_DEVIATION 1.105 • n=5 Participants
Global PDUS (MCP 2-5) score (n=96)	12.6 Units on a scale STANDARD_DEVIATION 4.1 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Days 7, 15, 29, 43, 57, 85, 113, 141, and 169

Population: 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.

Outcome measures

Outcome measures
Measure	Abatacept, 10 mg/kg n=96 Participants 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.
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 7 (n=86)	-0.7 Units on a scale 95% Confidence Interval 0.282 • Interval -1.2 to -0.1
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 15 (n=94)	-1.3 Units on a scale 95% Confidence Interval 0.308 • Interval -2.0 to -0.7
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 29 (n=95)	-2.4 Units on a scale 95% Confidence Interval 0.383 • Interval -3.2 to -1.7
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 43 (n=95)	-2.9 Units on a scale 95% Confidence Interval 0.384 • Interval -3.7 to -2.1
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 57 (n=95)	-3.2 Units on a scale 95% Confidence Interval 0.393 • Interval -4.0 to -2.4
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 85 (n=95)	-3.8 Units on a scale 95% Confidence Interval 0.454 • Interval -4.7 to -2.9
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 113 (n=95)	-4.5 Units on a scale 95% Confidence Interval 0.472 • Interval -5.4 to -3.5
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 141 (n=95)	-4.8 Units on a scale 95% Confidence Interval 0.492 • Interval -5.8 to -3.8
Mean Change From Baseline in Global Power Doppler Ultrasonography (PDUS) Score Assessing the Metacarpophalangeal (MCP) 2-5 Joints of Both Hands (LOCF Analysis) Day 169 (n=95)	-4.8 Units on a scale 95% Confidence Interval 0.473 • Interval -5.8 to -3.9

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Abatacept, 10 mg/kg n=96 Participants 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.
Earliest Time Point at Which Improvement of Core Component of the Global PDUS in the MCP (2-5) Joints of Both Hands Was Assessed	7 Day Interval -1.5 to -0.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Abatacept, 10 mg/kg n=96 Participants 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.
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Synovial hypertrophy (n=86): Day 7	-0.6 Units on a scale Standard Error 0.297
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Synovial hypertrophy (n=94): Day 15	-1.0 Units on a scale Standard Error 0.306
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Synovial hypertrophy (n=95): Day 29	-2.1 Units on a scale Standard Error 0.377
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Synovial hypertrophy (n=95): Day 169	-4.5 Units on a scale Standard Error 0.449
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Doppler signal: Day 7 (n=86)	-0.9 Units on a scale Standard Error 0.305
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Doppler signal: Day 15 (n=94)	-1.9 Units on a scale Standard Error 0.296
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Doppler signal: Day 29 (n=95)	-2.2 Units on a scale Standard Error 0.350
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Doppler signal: Day 169 (n=95)	-4.8 Units on a scale Standard Error 0.457
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Joint effusion: Day 7 (n=86)	0.1 Units on a scale Standard Error 0.237
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Joint effusion: Day 15 (n=94)	0.1 Units on a scale Standard Error 0.243
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Joint effusion: Day 29 (n=95)	-0.8 Units on a scale Standard Error 0.294
Mean Change From Baseline in Global PDUS MCP 2-5 Component Scores Over Time (LOCF Analysis) Joint effusion: Day 169 (n=95)	-1.9 Units on a scale Standard Error 0.351

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Abatacept, 10 mg/kg n=96 Participants 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.
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 Clinically meaningful improvement	0 Scores
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 Remission	0 Scores
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 Low disease activity	0 Scores

SECONDARY outcome

Timeframe: Days 1 to 169 to 56 days following last infusion

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

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.

Outcome measures

Outcome measures
Measure	Abatacept, 10 mg/kg n=104 Participants 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.
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 Deaths	0 Participants
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 SAEs	6 Participants
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 Treatment-related SAEs	2 Participants
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 Discontinuations due to SAEs	1 Participants
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 AEs	62 Participants
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 Treatment-related AEs	22 Participants
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 Discontinuations due to AEs	6 Participants

SECONDARY outcome

Timeframe: Days 1 to 169 to 56 days following last infusion

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

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.

Outcome measures

Outcome measures
Measure	Abatacept, 10 mg/kg n=104 Participants 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.
Number of Participants With Adverse Events (AEs) of Interest Infections	20 Participants
Number of Participants With Adverse Events (AEs) of Interest Malignancy	1 Participants
Number of Participants With Adverse Events (AEs) of Interest Autoimmune disorders (prespecified)	2 Participants
Number of Participants With Adverse Events (AEs) of Interest Infusion reactions (prespecified): Acute	4 Participants
Number of Participants With Adverse Events (AEs) of Interest Infusion reactions (prespecified): Periinfusional	10 Participants

Adverse Events

Aba 10 mg/kg

Serious events: 6 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aba 10 mg/kg n=104 participants at risk
Cardiac disorders Atrial fibrillation	0.96% 1/104
Infections and infestations Bursitis infective	0.96% 1/104
Respiratory, thoracic and mediastinal disorders Pulmonary fistula	0.96% 1/104
Nervous system disorders Dementia	0.96% 1/104
Reproductive system and breast disorders Endometriosis	0.96% 1/104
Vascular disorders Hypertension	0.96% 1/104
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.96% 1/104

Other adverse events

Other adverse events
Measure	Aba 10 mg/kg n=104 participants at risk
Respiratory, thoracic and mediastinal disorders Cough	8.7% 9/104
Infections and infestations Nasopharyngitis	6.7% 7/104

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER