Trial Outcomes & Findings for Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis (NCT NCT01142726)

Last Updated: 2016-01-14

Results Overview

DAS28-CRP remission defined as \<2.6; TP=treatment phase; WP=withdrawal phase. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

511 participants

Primary outcome timeframe

Randomization to Months 12 and 18

Results posted on

2016-01-14

Participant Flow

A total of 511 patients were enrolled in the study, and 351 were randomized. The primary reasons that 160 enrolled patients were not randomized were failure to meet study criteria (130/160) and withdrawal of consent (20/160).

Participant milestones

Participant milestones
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX.	Abatacept, 125 mg, Plus Methotrexate Placebo Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.	Methotrexate, 2.5 mg, Plus Abatacept Placebo Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Treatment Phase: Day 1 Through Month 12 STARTED	119	116	116
Treatment Phase: Day 1 Through Month 12 COMPLETED	103	91	96
Treatment Phase: Day 1 Through Month 12 NOT COMPLETED	16	25	20
Withdrawal Phase: Months 12 up to 24 STARTED	84	66	75
Withdrawal Phase: Months 12 up to 24 COMPLETED	14	10	17
Withdrawal Phase: Months 12 up to 24 NOT COMPLETED	70	56	58
Re-Exposure Phase: Months 24 up to 30 STARTED	55	48	43
Re-Exposure Phase: Months 24 up to 30 COMPLETED	54	46	40
Re-Exposure Phase: Months 24 up to 30 NOT COMPLETED	1	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg Participants received abatacept, 125 mg subcutaneously, plus methotrexate (MTX), 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept subcutaneous (SC) 125 mg/week and MTX.	Abatacept, 125 mg, Plus Methotrexate Placebo Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.	Methotrexate, 2.5 mg, Plus Abatacept Placebo Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a Low Disease Activity Score (LDAS) defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of rheumatoid arthritis (RA) symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX.
Treatment Phase: Day 1 Through Month 12 Adverse Event	5	8	5
Treatment Phase: Day 1 Through Month 12 Withdrawal by Subject	4	9	3
Treatment Phase: Day 1 Through Month 12 Lost to Follow-up	1	2	1
Treatment Phase: Day 1 Through Month 12 Poor compliance/noncompliance	1	0	0
Treatment Phase: Day 1 Through Month 12 Lack of Efficacy	5	6	11
Withdrawal Phase: Months 12 up to 24 Adverse Event	0	0	1
Withdrawal Phase: Months 12 up to 24 Withdrawal by Subject	1	1	2
Withdrawal Phase: Months 12 up to 24 Pregnancy	1	0	1
Withdrawal Phase: Months 12 up to 24 Lost to Follow-up	2	0	0
Withdrawal Phase: Months 12 up to 24 No longer met study criteria	1	0	0
Withdrawal Phase: Months 12 up to 24 Lack of Efficacy	65	54	53
Withdrawal Phase: Months 12 up to 24 non-specified	0	1	1
Re-Exposure Phase: Months 24 up to 30 Adverse Event	0	0	1
Re-Exposure Phase: Months 24 up to 30 Withdrawal by Subject	1	1	1
Re-Exposure Phase: Months 24 up to 30 Pregnancy	0	0	1
Re-Exposure Phase: Months 24 up to 30 Lack of Efficacy	0	1	0

Baseline Characteristics

Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Abatacept, 125 mg, Plus Methotrexate Placebo n=116 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Total n=351 Participants Total of all reporting groups
Age, Continuous	46.4 Years STANDARD_DEVIATION 13.20 • n=93 Participants	45.4 Years STANDARD_DEVIATION 11.92 • n=4 Participants	49.1 Years STANDARD_DEVIATION 12.36 • n=27 Participants	47.0 Years STANDARD_DEVIATION 12.57 • n=483 Participants
Sex: Female, Male Female	95 Participants n=93 Participants	89 Participants n=4 Participants	89 Participants n=27 Participants	273 Participants n=483 Participants
Sex: Female, Male Male	24 Participants n=93 Participants	27 Participants n=4 Participants	27 Participants n=27 Participants	78 Participants n=483 Participants
Race/Ethnicity, Customized White	100 Participants n=93 Participants	95 Participants n=4 Participants	102 Participants n=27 Participants	297 Participants n=483 Participants
Race/Ethnicity, Customized Asian	14 Participants n=93 Participants	13 Participants n=4 Participants	9 Participants n=27 Participants	36 Participants n=483 Participants
Race/Ethnicity, Customized Black/African American	2 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	8 Participants n=483 Participants
Race/Ethnicity, Customized American Indian/Alaska native	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants
Race/Ethnicity, Customized Other	2 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	7 Participants n=483 Participants
Duration of rheumatoid arthritis	0.58 Years STANDARD_DEVIATION 0.500 • n=93 Participants	0.59 Years STANDARD_DEVIATION 0.522 • n=4 Participants	0.50 Years STANDARD_DEVIATION 0.488 • n=27 Participants	0.56 Years STANDARD_DEVIATION 0.504 • n=483 Participants
Disease Activity Score 28 based on C-reactive protein (DAS28-CRP)	5.528 Units on a scale STANDARD_DEVIATION 1.2501 • n=93 Participants	5.463 Units on a scale STANDARD_DEVIATION 1.1493 • n=4 Participants	5.315 Units on a scale STANDARD_DEVIATION 1.3330 • n=27 Participants	5.435 Units on a scale STANDARD_DEVIATION 1.2465 • n=483 Participants
Health Assessment Questionnaire Disability Index (HAQ-DI) score	1.452 Units on a scale STANDARD_DEVIATION 0.6778 • n=93 Participants	1.419 Units on a scale STANDARD_DEVIATION 0.6587 • n=4 Participants	1.383 Units on a scale STANDARD_DEVIATION 0.6493 • n=27 Participants	1.419 Units on a scale STANDARD_DEVIATION 0.6609 • n=483 Participants
Rheumatoid factor status Positive	113 Participants n=93 Participants	111 Participants n=4 Participants	110 Participants n=27 Participants	334 Participants n=483 Participants
Rheumatoid factor status Negative	6 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	17 Participants n=483 Participants
Tender joint count	24.3 Joints STANDARD_DEVIATION 15.74 • n=93 Participants	23.9 Joints STANDARD_DEVIATION 14.47 • n=4 Participants	21.7 Joints STANDARD_DEVIATION 14.00 • n=27 Participants	23.3 Joints STANDARD_DEVIATION 14.77 • n=483 Participants
Swollen joint count	16.5 Joints STANDARD_DEVIATION 12.43 • n=93 Participants	17.2 Joints STANDARD_DEVIATION 12.88 • n=4 Participants	15.7 Joints STANDARD_DEVIATION 11.78 • n=27 Participants	16.5 Joints STANDARD_DEVIATION 12.35 • n=483 Participants

PRIMARY outcome

Timeframe: Randomization to Months 12 and 18

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Month 12 and at both Months 12 and 18, and b=number of patients in the analysis. n=number evaluable

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18 Month 12 (TP Day 365) (n=115, 115)	60.9 Percentage of participants	45.2 Percentage of participants	—
Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18 Both Months 12 & 18 (WP Day 169) (n=115, 115)	14.8 Percentage of participants	7.8 Percentage of participants	—

SECONDARY outcome

Timeframe: Randomization to Months 12 and 18

Population: All randomized participants who received at least 1 dose of double-blind monotherapy in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Month 12 and at both Months 12 and 18, and b=number of patients in the analysis. n=number evaluable

TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP\<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=116 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18 At Month 12 (TP Day 365) (n=113, 115)	42.5 Percentage of participants Interval 33.36 to 51.59	45.2 Percentage of participants Interval 36.12 to 54.31	—
Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18 At both Months 12 &18 (WP Day 169) (n=113, 115)	12.4 Percentage of participants Interval 6.31 to 18.46	7.8 Percentage of participants Interval 2.92 to 12.73	—

SECONDARY outcome

Timeframe: Randomization to Month 24

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Day x, and b=number of patients in the analysis (intent to treat).

TP=treatment period; WP=withdrawal period. Remission defined as DAS28-CRP\<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 29	13.4 Percentage of participants Interval 7.32 to 19.57	8.6 Percentage of participants Interval 3.51 to 13.73	6.0 Percentage of participants Interval 1.7 to 10.37
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 57	24.4 Percentage of participants Interval 16.66 to 32.08	11.2 Percentage of participants Interval 5.47 to 16.95	9.5 Percentage of participants Interval 4.15 to 14.81
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 85	36.1 Percentage of participants Interval 27.5 to 44.77	21.6 Percentage of participants Interval 14.07 to 29.03	17.2 Percentage of participants Interval 10.37 to 24.12
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 113	37.8 Percentage of participants Interval 29.1 to 46.53	29.3 Percentage of participants Interval 21.03 to 37.59	19.0 Percentage of participants Interval 11.83 to 26.1
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 141	45.4 Percentage of participants Interval 36.43 to 54.32	29.3 Percentage of participants Interval 21.03 to 37.59	25.0 Percentage of participants Interval 17.12 to 32.88
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 169	45.4 Percentage of participants Interval 36.43 to 54.32	32.8 Percentage of participants Interval 24.22 to 41.3	26.7 Percentage of participants Interval 18.67 to 34.78
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 197	52.1 Percentage of participants Interval 43.13 to 61.08	36.2 Percentage of participants Interval 27.46 to 44.95	25.9 Percentage of participants Interval 17.89 to 33.83
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 225	57.1 Percentage of participants Interval 48.25 to 66.03	40.5 Percentage of participants Interval 31.58 to 49.45	30.2 Percentage of participants Interval 21.82 to 38.53
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 253	62.2 Percentage of participants Interval 53.47 to 70.9	37.9 Percentage of participants Interval 29.1 to 46.76	30.2 Percentage of participants Interval 21.82 to 38.53
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP 281	51.3 Percentage of participants Interval 42.28 to 60.24	42.2 Percentage of participants Interval 33.25 to 51.23	32.8 Percentage of participants Interval 24.22 to 41.3
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP 309	56.3 Percentage of participants Interval 47.39 to 65.21	37.9 Percentage of participants Interval 29.1 to 46.76	36.2 Percentage of participants Interval 27.46 to 44.95
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP Day 337	63.0 Percentage of participants Interval 54.35 to 71.7	43.1 Percentage of participants Interval 34.09 to 52.12	33.6 Percentage of participants Interval 25.02 to 42.22
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population TP 365	61.3 Percentage of participants Interval 52.6 to 70.09	43.1 Percentage of participants Interval 34.09 to 52.12	45.7 Percentage of participants Interval 36.62 to 54.75
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population WP Day 29	51.3 Percentage of participants Interval 42.28 to 60.24	36.2 Percentage of participants Interval 27.46 to 44.95	27.6 Percentage of participants Interval 19.45 to 35.72
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population WP Day 57	40.3 Percentage of participants Interval 31.52 to 49.15	25.0 Percentage of participants Interval 17.12 to 32.88	18.1 Percentage of participants Interval 11.1 to 25.11
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population WP Day 85	31.1 Percentage of participants Interval 22.78 to 39.41	18.1 Percentage of participants Interval 11.1 to 25.11	18.1 Percentage of participants Interval 11.1 to 25.11
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population WP Day 169	19.3 Percentage of participants Interval 12.23 to 26.42	12.9 Percentage of participants Interval 6.82 to 19.04	9.5 Percentage of participants Interval 4.15 to 14.81
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population WP Day 253	17.6 Percentage of participants Interval 10.8 to 24.5	9.5 Percentage of participants Interval 4.15 to 14.81	13.8 Percentage of participants Interval 7.52 to 20.07
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population WP Day 365	9.2 Percentage of participants Interval 4.04 to 14.45	6.0 Percentage of participants Interval 1.7 to 10.37	6.0 Percentage of participants Interval 1.7 to 10.37

SECONDARY outcome

Timeframe: Baseline to Month 18

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable

TP=treatment period; WP=withdrawal period. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18 Month 6 (TP Day 169) (n=102, 96, 101)	-2.72 Units on a scale Standard Error 0.12	-2.33 Units on a scale Standard Error 0.12	-1.93 Units on a scale Standard Error 0.12
Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18 Month 12 (TP Day 365) (n=95, 84, 91)	-3.09 Units on a scale Standard Error 0.13	-2.75 Units on a scale Standard Error 0.13	-2.58 Units on a scale Standard Error 0.13
Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18 Month 18 (WP Day 169) (n=41, 31, 32)	-1.54 Units on a scale Standard Error 0.26	-1.51 Units on a scale Standard Error 0.29	-1.06 Units on a scale Standard Error 0.29

SECONDARY outcome

Timeframe: Randomization to Month 18

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Percentage calculated as a/b, where a=number of patients who achieved remission at Months 12 and 18, and b=number of patients in the analysis.

TP=treatment period; WP=withdrawal period. SDAI-defined remission= ≤3.3. The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11=low disease activity, \>11 to 26=moderate disease activity, and \>26=high disease activity. TJC is assessed and recorded at each visit, with no swelling=0, swelling=1. SJC is assessed through identification of joints that are painful under pressure or to passive motion. TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1. Higher score indicates greater affection due to disease activity.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18 Month 12 (TP Day 365)	42.0 Percentage of participants Interval 33.15 to 50.89	29.3 Percentage of participants Interval 21.03 to 37.59	25.0 Percentage of participants Interval 17.12 to 32.88
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18 Month 18 (WP Day 169)	10.9 Percentage of participants Interval 5.32 to 16.53	8.6 Percentage of participants Interval 3.51 to 13.73	6.9 Percentage of participants Interval 2.29 to 11.51

SECONDARY outcome

Timeframe: Randomization to Month 18

Population: Intent to Treat (ITT) population. n= number of participants with both post baseline and baseline measurements.

TP=treatment period; WP=withdrawal period. The SDAI is the simple linear sum of 5 outcome parameters: swollen joint count (SJC) and tender joint count (TJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL). SDAI total score=0-86. SJC is assessed and recorded at each visit, with no swelling=0, swelling=1 (higher score indicates greater swelling). TJC is assessed at each visit through identification of joints that are painful under pressure or to passive motion, with no tenderness=0, tenderness=1 (higher score indicates greater affection due to disease activity)..

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 337 (n=93, 84, 87)	-31.11 Units on a scale Standard Error 1.15	-29.34 Units on a scale Standard Error 1.19	-27.26 Units on a scale Standard Error 1.17
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP 365 (n=95, 84, 91)	-31.24 Units on a scale Standard Error 1.17	-28.88 Units on a scale Standard Error 1.21	-28.34 Units on a scale Standard Error 1.19
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 29 (n=109, 101, 107)	-13.11 Units on a scale Standard Error 1.33	-12.14 Units on a scale Standard Error 1.37	-10.12 Units on a scale Standard Error 1.33
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 57 (n=108, 101, 103)	-18.90 Units on a scale Standard Error 1.25	-15.83 Units on a scale Standard Error 1.28	-15.99 Units on a scale Standard Error 1.26
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 85 (n=108, 99, 103)	-24.13 Units on a scale Standard Error 1.16	-20.51 Units on a scale Standard Error 1.20	-19.55 Units on a scale Standard Error 1.17
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 113 (n=103, 98, 101)	-25.47 Units on a scale Standard Error 1.12	-23.56 Units on a scale Standard Error 1.15	-21.02 Units on a scale Standard Error 1.13
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 141 (n=104, 96, 104)	-27.15 Units on a scale Standard Error 1.10	-25.99 Units on a scale Standard Error 1.13	-22.14 Units on a scale Standard Error 1.10
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 169 (n=102, 96, 100)	-28.42 Units on a scale Standard Error 1.08	-26.20 Units on a scale Standard Error 1.11	-22.80 Units on a scale Standard Error 1.09
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 197 (n=103, 97, 96)	-29.66 Units on a scale Standard Error 1.01	-27.57 Units on a scale Standard Error 1.03	-24.37 Units on a scale Standard Error 1.02
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 225 (n=99, 94, 92)	-30.13 Units on a scale Standard Error 1.04	-28.39 Units on a scale Standard Error 1.06	-24.73 Units on a scale Standard Error 1.06
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP Day 253 (n=98, 94, 91)	-31.14 Units on a scale Standard Error 1.04	-28.10 Units on a scale Standard Error 1.06	-25.80 Units on a scale Standard Error 1.05
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP 281 (n=96, 93, 89)	-30.98 Units on a scale Standard Error 1.10	-28.16 Units on a scale Standard Error 1.12	-26.23 Units on a scale Standard Error 1.12
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time TP 309 (n=91, 87, 92)	-30.82 Units on a scale Standard Error 1.16	-27.79 Units on a scale Standard Error 1.18	-26.36 Units on a scale Standard Error 1.17
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time WP Day 29 (n=73, 59, 64)	-30.42 Units on a scale Standard Error 1.32	-28.05 Units on a scale Standard Error 1.39	-23.52 Units on a scale Standard Error 1.36
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time WP Day 57 (n=69, 54, 59)	-27.68 Units on a scale Standard Error 1.59	-24.17 Units on a scale Standard Error 1.74	-17.94 Units on a scale Standard Error 1.68
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time WP Day 85 (n=67, 47, 52)	-22.00 Units on a scale Standard Error 2.18	-21.55 Units on a scale Standard Error 2.57	-17.54 Units on a scale Standard Error 2.44
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time WP Day 169 (n=41, 31, 32)	-17.43 Units on a scale Standard Error 2.82	-19.13 Units on a scale Standard Error 3.25	-13.64 Units on a scale Standard Error 3.19

SECONDARY outcome

Timeframe: Randomization to Month 24

HAQ response defined as a reduction of at least 0.3 units from baseline in score on the Health Assessment Questionnaire Disability Index (HAQ-DI), which assesses patients' functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 169	63.9 Percentage of participants Interval 55.23 to 72.5	56.0 Percentage of participants Interval 47.0 to 65.07	41.4 Percentage of participants Interval 32.42 to 50.34
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 197	66.4 Percentage of participants Interval 57.9 to 74.87	59.5 Percentage of participants Interval 50.55 to 68.42	41.4 Percentage of participants Interval 32.42 to 50.34
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 225	66.4 Percentage of participants Interval 57.9 to 74.87	57.8 Percentage of participants Interval 48.77 to 66.75	38.8 Percentage of participants Interval 29.93 to 47.66
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 253	68.9 Percentage of participants Interval 60.59 to 77.22	55.2 Percentage of participants Interval 46.12 to 64.22	45.7 Percentage of participants Interval 36.62 to 54.75
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 281	64.7 Percentage of participants Interval 56.12 to 73.29	56.9 Percentage of participants Interval 47.88 to 65.91	46.6 Percentage of participants Interval 37.47 to 55.63
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 309	65.5 Percentage of participants Interval 57.01 to 74.08	56.9 Percentage of participants Interval 47.88 to 65.91	46.6 Percentage of participants Interval 37.47 to 55.63
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 337	64.7 Percentage of participants Interval 56.12 to 73.29	55.2 Percentage of participants Interval 46.12 to 64.22	46.6 Percentage of participants Interval 37.47 to 55.63
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 365	67.2 Percentage of participants Interval 58.79 to 75.66	52.6 Percentage of participants Interval 43.5 to 61.67	44.0 Percentage of participants Interval 34.93 to 53.0
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time WP Day 29	52.1 Percentage of participants Interval 43.13 to 61.08	39.7 Percentage of participants Interval 30.75 to 48.56	37.1 Percentage of participants Interval 28.28 to 45.86
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time WP Day 57	43.7 Percentage of participants Interval 34.79 to 52.61	34.5 Percentage of participants Interval 25.83 to 43.13	26.7 Percentage of participants Interval 18.67 to 34.78
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time WP Day 85	39.5 Percentage of participants Interval 30.71 to 48.28	28.4 Percentage of participants Interval 20.24 to 36.66	23.3 Percentage of participants Interval 15.59 to 30.97
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time WP Day 169	22.7 Percentage of participants Interval 15.16 to 30.21	16.4 Percentage of participants Interval 9.64 to 23.11	10.3 Percentage of participants Interval 4.8 to 15.89
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time WP Day 253	15.1 Percentage of participants Interval 8.69 to 21.56	9.5 Percentage of participants Interval 4.15 to 14.81	6.9 Percentage of participants Interval 2.29 to 11.51
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time WP Day 365	10.1 Percentage of participants Interval 4.67 to 15.49	6.9 Percentage of participants Interval 2.29 to 11.51	5.2 Percentage of participants Interval 1.14 to 9.2
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 29	42.0 Percentage of participants Interval 33.15 to 50.89	31.0 Percentage of participants Interval 22.62 to 39.45	21.6 Percentage of participants Interval 14.07 to 29.03
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 57	55.5 Percentage of participants Interval 46.53 to 64.39	44.0 Percentage of participants Interval 34.93 to 53.0	37.9 Percentage of participants Interval 29.1 to 46.76
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 85	63.0 Percentage of participants Interval 54.35 to 71.7	45.7 Percentage of participants Interval 36.62 to 54.75	41.4 Percentage of participants Interval 32.42 to 50.34
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 113	63.0 Percentage of participants Interval 54.35 to 71.7	49.1 Percentage of participants Interval 40.04 to 58.24	45.7 Percentage of participants Interval 36.62 to 54.75
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time TP Day 141	62.2 Percentage of participants Interval 53.47 to 70.9	51.7 Percentage of participants Interval 42.63 to 60.82	44.0 Percentage of participants Interval 34.93 to 53.0

SECONDARY outcome

Timeframe: Randomization to Month 18

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable

The Health Assessment Questionnaire Disability Index (HAQ-DI) assesses patients' functional ability by rating their abilities over the previous week. The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities. Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3. When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 29 (n=104, 103, 91)	-0.33 Units on a scale Standard Error 0.05	-0.21 Units on a scale Standard Error 0.05	-0.09 Units on a scale Standard Error 0.05
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 57 (n=102, 100, 93)	-0.48 Units on a scale Standard Error 0.05	-0.38 Units on a scale Standard Error 0.05	-0.32 Units on a scale Standard Error 0.05
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 85 (n=105, 97, 88)	-0.64 Units on a scale Standard Error 0.05	-0.45 Units on a scale Standard Error 0.05	-0.40 Units on a scale Standard Error 0.05
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 113 (n=105, 98, 90)	-0.67 Units on a scale Standard Error 0.05	-0.55 Units on a scale Standard Error 0.05	-0.50 Units on a scale Standard Error 0.05
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 141 (n=100, 98, 88)	-0.72 Units on a scale Standard Error 0.05	-0.53 Units on a scale Standard Error 0.05	-0.46 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 169 (n=95, 95, 85)	-0.74 Units on a scale Standard Error 0.05	-0.59 Units on a scale Standard Error 0.05	-0.52 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 197 (n=99, 96, 83)	-0.78 Units on a scale Standard Error 0.05	-0.62 Units on a scale Standard Error 0.06	-0.54 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 225 (n=98, 95, 83)	-0.79 Units on a scale Standard Error 0.06	-0.67 Units on a scale Standard Error 0.06	-0.56 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 253 (n=96, 91, 84)	-0.82 Units on a scale Standard Error 0.05	-0.65 Units on a scale Standard Error 0.06	-0.63 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 281 (n=90, 93, 81)	-0.82 Units on a scale Standard Error 0.06	-0.65 Units on a scale Standard Error 0.06	-0.62 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 309 (n=89, 88, 82)	-0.81 Units on a scale Standard Error 0.06	-0.67 Units on a scale Standard Error 0.06	-0.66 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 337 (n=88, 85, 80)	-0.84 Units on a scale Standard Error 0.06	-0.70 Units on a scale Standard Error 0.06	-0.70 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time TP Day 365 (n=90, 82, 77)	-0.87 Units on a scale Standard Error 0.06	-0.73 Units on a scale Standard Error 0.06	-0.72 Units on a scale Standard Error 0.06
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time WP Day 29 (n=70, 55, 55)	-0.85 Units on a scale Standard Error 0.06	-0.67 Units on a scale Standard Error 0.07	-0.63 Units on a scale Standard Error 0.07
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time WP Day 57 (n=66, 53, 54)	-0.67 Units on a scale Standard Error 0.07	-0.58 Units on a scale Standard Error 0.08	-0.39 Units on a scale Standard Error 0.08
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time WP Day 85 (n=65, 45, 46)	-0.54 Units on a scale Standard Error 0.08	-0.48 Units on a scale Standard Error 0.09	-0.37 Units on a scale Standard Error 0.09
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time WP Day 169 (n=34, 28, 26)	-0.52 Units on a scale Standard Error 0.10	-0.49 Units on a scale Standard Error 0.11	-0.33 Units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Randomization to Months 6, 12, and 18

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable

TP=treatment period; WP=withdrawal period. The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health). Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36) PCS score TP Day 169 (n=106, 95, 96)	11.68 Units on a scale Standard Error 0.82	9.16 Units on a scale Standard Error 0.86	7.47 Units on a scale Standard Error 0.85
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36) PCS score TP Day 365 (n=94, 88, 91)	13.91 Units on a scale Standard Error 0.93	10.23 Units on a scale Standard Error 0.97	10.92 Units on a scale Standard Error 0.95
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36) PCS score WP Day 169 (n=48, 36, 37)	6.16 Units on a scale Standard Error 1.45	4.59 Units on a scale Standard Error 1.65	6.27 Units on a scale Standard Error 1.63
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36) MCS score TP Day 169 (n=106, 95, 96)	6.11 Units on a scale Standard Error 0.92	3.99 Units on a scale Standard Error 0.97	4.69 Units on a scale Standard Error 0.95
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36) MCS score TP Day 365 (n=94, 88, 91)	7.67 Units on a scale Standard Error 1.04	5.48 Units on a scale Standard Error 1.08	7.23 Units on a scale Standard Error 1.06
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36) MCS score WP Day 169 (n=48, 36, 37)	2.75 Units on a scale Standard Error 1.44	4.36 Units on a scale Standard Error 1.64	2.23 Units on a scale Standard Error 1.63

SECONDARY outcome

Timeframe: Randomization to Month 18

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=the number of patients with both baseline and postbaseline measurements.

TP=treatment period; WP=withdrawal period. Change from Baseline=Postbaseline-baseline value. MRI was used to assess joint damage progression at Months 6, 12, and 18. If \>20% of joints with a missing score for a parameter (erosion, osteitis, and synovitis), the MRI score of each parameter was considered missing. If ≤20% of joints had a missing score for a parameter, the MRI score for that parameter from the missing joints was carried forward from the previous MRI assessment, or carried backward from the next MRI assessment, if missing score occurred at baseline. MRI total score ranged from 0 (best outcome) to 4 (worst outcome). A gadolinium-enhanced MRI of the dominant hand-wrist was performed on all randomized patients at 5 points. The hand/wrist assessed to have more synovitis was selected initially and used for all subsequent evaluations. The MRI examination was standardized to ensure sufficient image quality for the evaluation of radiographic progression of rheumatoid arthritis.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Synovitis TP Day 169 (n=93, 94, 89)	-1.82 Units on a scale Standard Error 0.21	-0.93 Units on a scale Standard Error 0.21	-0.78 Units on a scale Standard Error 0.21
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Synovitis TP Day 365 (n=83, 74, 78)	-2.38 Units on a scale Standard Error 0.29	-1.36 Units on a scale Standard Error 0.30	-0.77 Units on a scale Standard Error 0.30
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Synovitis WP Day 169 (n=31, 30, 25))	-1.71 Units on a scale Standard Error 0.45	-0.95 Units on a scale Standard Error 0.45	-0.71 Units on a scale Standard Error 0.49
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Osteitis TP Day 169 (n=93, 94, 89)	-2.03 Units on a scale Standard Error 0.47	-1.13 Units on a scale Standard Error 0.47	-0.73 Units on a scale Standard Error 0.48
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Osteitis TP Day 365 (n=83, 74, 78)	-2.32 Units on a scale Standard Error 0.46	-1.30 Units on a scale Standard Error 0.46	-0.90 Units on a scale Standard Error 0.46
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Osteitis WP Day 169 (n=31, 30, 25)	-1.94 Units on a scale Standard Error 0.88	0.98 Units on a scale Standard Error 0.89	-0.33 Units on a scale Standard Error 0.96
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Erosion TP Day 169 (n=93, 94, 89)	0.26 Units on a scale Standard Error 0.28	1.15 Units on a scale Standard Error 0.28	1.15 Units on a scale Standard Error 0.28
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Erosion TP Day 365 (n=83, 74, 78)	0.34 Units on a scale Standard Error 0.35	1.57 Units on a scale Standard Error 0.36	1.56 Units on a scale Standard Error 0.36
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) Erosion WP Day 169 (n=31, 30, 25)	0.20 Units on a scale Standard Error 0.47	2.16 Units on a scale Standard Error 0.48	1.89 Units on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period Deaths	0 Participants	0 Participants	2 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period SAEs	8 Participants	14 Participants	9 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period Related SAEs	3 Participants	3 Participants	1 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period Discontinuations due to SAEs	2 Participants	5 Participants	3 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period Related AEs	53 Participants	48 Participants	51 Participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period Discontinuations due to AEs	4 Participants	8 Participants	5 Participants

SECONDARY outcome

Timeframe: Day 1 to 56 days following last dosing day (Day 365)

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adverse Events (AEs) of Interest During the Treatment Period Infections	68 Participants	64 Participants	69 Participants
Adverse Events (AEs) of Interest During the Treatment Period Malignancy	1 Participants	2 Participants	1 Participants
Adverse Events (AEs) of Interest During the Treatment Period Autoimmune disorders (prespecified)	1 Participants	2 Participants	3 Participants
Adverse Events (AEs) of Interest During the Treatment Period Local injection site reactions (prespecified)	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. n=number evaluable

Lower limit of normal (LLN); Upper limit of normal (ULN); Pretreatment (preRX). Criteria for marked abnormality: Platelet count (\*10\^9 c/µL) \<0.67\*LLN or \>1.5\*ULN, or if preRX\<LLN, use 0.5\*preRX and \<100,000/mm\^3; potassium, serum (mEq) \<0.9\*LLN or \>1.1\*ULN, or if preRX \<LLN, use \<0.9\*preRX or \>ULN if preRX\>ULN, use \>1.1\*preRX or \<LLN; blood urea nitrogen (mg/dL) \>2\*preRX; creatinine (mg/dL) \>1.5\*preRX; ALT (U/L) \>3\*ULN, or if preRX\>ULN, use \>4\*preRX; AST (U/L) \>3\*ULN, or if preRX\>ULN, use \>4\*preRX; ALP (U/L) \>2\*ULN, or if preRX\>ULN, use \>3\*preRX; G-glutamyl transferase U/L) \>2\*ULN, or if preRX\>ULN, use \>3\*preRX; glucose, fasting (mg/dL) \<0.8\*LLN or \>1.5\*ULN, or if preRX\<LLN use \<0.8\*preRX or \>ULN if preRX \>ULN, use \>2.0\*preRX or OR \<LLN; glucose, serum (mg/dL) \<65 or \>220; uric acid (mg/dL)\>1.5\*ULN, or if preRX, use \>2\*preRX; albumin (g/dL) \<0.9\*LLN, or if preRX\<LLN, use \<0.75\*preRX; hemoglobin (g/dL)\>3 decrease from preRX; hematocrit (%) \< 0.75\*preRX.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Platelet count (high) (n=119, 116, 115)	2 Participants	0 Participants	0 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Potassium, serum (low)	1 Participants	1 Participants	1 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Blood urea nitrogen (high)	4 Participants	1 Participants	2 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Creatinine (high)	2 Participants	1 Participants	3 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Alanine aminotransferase (ALT)(high)	3 Participants	0 Participants	2 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Aspartate aminotransferase (AST)(high)	2 Participants	0 Participants	1 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period G-glutamyl transferase (GGT) (high)	3 Participants	1 Participants	1 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Glucose, fasting (low) (n=78, 72, 75)	2 Participants	0 Participants	2 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Glucose, fasting (high) (n=78, 72, 75)	1 Participants	2 Participants	1 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Glucose, serum (low) (n=84, 78, 75)	5 Participants	6 Participants	2 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Glucose, serum (high) (n=84, 78, 75)	1 Participants	4 Participants	3 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Uric acid (high)	0 Participants	1 Participants	0 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Albumin (low)	1 Participants	1 Participants	4 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Hemoglobin (low) (n=119, 116, 115)	0 Participants	2 Participants	0 Participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period Hematocrit (low) (n=119, 116, 115)	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)

Population: Treated participants who were in remission at Month 12 (DAS28-CRP\<2.6) and entered the Withdrawal Period were analyzed.( N=number of participants analyzed).

WP=withdrawal period. Remission defined as DAS28-CRP\<2.6. The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity. Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.). Percentage= number of participants with remission divided by number of participants who were analyzed (all treated participants who were in remission at end of treatment period and entered the Withdrawal Period)

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=73 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=50 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=53 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12 WP Day 29	73.3 percentage of participants Interval 65.46 to 85.23	72.0 percentage of participants Interval 59.55 to 84.45	54.7 percentage of participants Interval 41.32 to 68.12
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12 WP Day 57	58.9 percentage of participants Interval 47.62 to 70.19	56.0 percentage of participants Interval 42.24 to 69.76	32.1 percentage of participants Interval 19.51 to 44.64
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12 WP Day 85	42.5 percentage of participants Interval 31.13 to 53.8	40.0 percentage of participants Interval 26.42 to 53.58	35.8 percentage of participants Interval 22.94 to 48.76
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12 WP Day 169	26.0 percentage of participants Interval 15.96 to 36.09	30.0 percentage of participants Interval 17.3 to 42.7	17.0 percentage of participants Interval 6.87 to 27.09
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12 WP Day 253	20.5 percentage of participants Interval 11.28 to 29.82	22.0 percentage of participants Interval 10.52 to 33.48	20.8 percentage of participants Interval 9.84 to 31.67
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12 WP Day 365	12.3 percentage of participants Interval 4.79 to 19.87	14.0 percentage of participants Interval 4.38 to 23.62	11.3 percentage of participants Interval 2.79 to 19.85

SECONDARY outcome

Timeframe: Randomization to Month 24

Population: ITT analysis population: Included all randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period. Participants were grouped according to the treatment regimen to which they were randomized.N= number evaluated.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 225	38.7 percentage of participants Interval 29.91 to 47.4	25.9 percentage of participants Interval 17.89 to 33.83	14.7 percentage of participants Interval 8.22 to 21.09
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 253	37.8 percentage of participants Interval 29.1 to 46.53	25.0 percentage of participants Interval 17.12 to 32.88	13.8 percentage of participants Interval 7.52 to 20.07
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 281	37.8 percentage of participants Interval 29.1 to 46.53	26.7 percentage of participants Interval 18.67 to 34.78	18.1 percentage of participants Interval 11.1 to 25.11
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 309	40.3 percentage of participants Interval 31.52 to 49.15	26.7 percentage of participants Interval 18.67 to 34.78	19.0 percentage of participants Interval 11.83 to 26.1
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 29	4.2 percentage of participants Interval 1.38 to 9.53	3.4 percentage of participants Interval 0.95 to 8.59	1.7 percentage of participants Interval 0.21 to 6.09
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 57	9.2 percentage of participants Interval 4.71 to 15.94	6.0 percentage of participants Interval 2.46 to 12.04	1.7 percentage of participants Interval 0.21 to 6.09
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 85	17.6 percentage of participants Interval 10.8 to 24.5	8.6 percentage of participants Interval 3.51 to 13.73	6.0 percentage of participants Interval 1.7 to 10.37
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 113	23.5 percentage of participants Interval 15.91 to 31.15	17.2 percentage of participants Interval 10.37 to 24.12	7.8 percentage of participants Interval 2.89 to 12.63
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 141	31.9 percentage of participants Interval 23.56 to 40.31	23.3 percentage of participants Interval 15.59 to 30.97	10.3 percentage of participants Interval 4.8 to 15.89
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 169	31.1 percentage of participants Interval 22.78 to 39.41	20.7 percentage of participants Interval 13.32 to 28.06	11.2 percentage of participants Interval 5.47 to 16.95
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 197	33.6 percentage of participants Interval 25.13 to 42.1	21.6 percentage of participants Interval 14.07 to 29.03	12.9 percentage of participants Interval 6.82 to 19.04
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 337	41.2 percentage of participants Interval 32.33 to 50.02	31.0 percentage of participants Interval 22.62 to 39.45	19.0 percentage of participants Interval 11.83 to 26.1
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period TP Day 365	42.0 percentage of participants Interval 33.15 to 50.89	29.3 percentage of participants Interval 21.03 to 37.59	25.0 percentage of participants Interval 17.12 to 32.88
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period WP Day 29	38.7 percentage of participants Interval 29.91 to 47.4	26.7 percentage of participants Interval 18.67 to 34.78	14.7 percentage of participants Interval 8.22 to 21.09
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period WP Day 57	26.9 percentage of participants Interval 18.92 to 34.86	20.7 percentage of participants Interval 13.32 to 28.06	10.3 percentage of participants Interval 4.8 to 15.89
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period WP Day 85	21.0 percentage of participants Interval 13.69 to 28.33	15.5 percentage of participants Interval 8.93 to 22.11	14.7 percentage of participants Interval 8.22 to 21.09
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period WP Day 169	11.8 percentage of participants Interval 5.98 to 17.55	9.5 percentage of participants Interval 4.15 to 14.81	6.9 percentage of participants Interval 2.29 to 11.51
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period WP Day 253	11.8 percentage of participants Interval 5.98 to 17.55	9.5 percentage of participants Interval 4.15 to 14.81	7.8 percentage of participants Interval 2.89 to 12.63
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period WP Day 365	6.7 percentage of participants Interval 2.22 to 11.22	4.3 percentage of participants Interval 0.61 to 8.01	4.3 percentage of participants Interval 0.61 to 8.01

SECONDARY outcome

Timeframe: Day 1 to 56 days post last dose in the study, up to Month 30

Population: All randomized participants who received at least 1 dose of study medication were analyzed.

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. Includes data up to last active dose date +56 days if the participant discontinued the Treatment Period or did not enter the Withdrawal Period, up to the day of discontinuation in the Withdrawal Period for participants discontinuing the Withdrawal Period without entering the Re-exposure Period (RP), up to Day 729 visit (Month 24) for participants who complete the Withdrawal Period, and up to 56 days post last active dose in Re-exposure Period for participants entering the Re-exposure Period.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods) Death	0 participants	0 participants	2 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods) SAE	11 participants	15 participants	15 participants
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods) Discontinued Due to AE	4 participants	8 participants	7 participants

SECONDARY outcome

Timeframe: Last dose in TP + 57 days, up to Month 24

Population: All randomized participants who received at least 1 dose of double-blind study medication in the Treatment Period and entered the Withdrawal Period. Treatment groups represent treatment during the TP.

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. AEs of special interest are events potentially associated with the drug or disease under study. Includes events with an onset date on or after 57 days post last dosing day (active abatacept or active MTX whichever is the later) in the Treatment Period and up to end of Withdrawal Period. Treatment groups represent treatment received during the Treatment Period.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=84 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=66 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=75 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adverse Events (AEs) of Interest During the Withdrawal Period Infections	8 participants	6 participants	10 participants
Adverse Events (AEs) of Interest During the Withdrawal Period Malignancy	1 participants	0 participants	1 participants
Adverse Events (AEs) of Interest During the Withdrawal Period Autoimmune disorders (prespecified)	0 participants	0 participants	1 participants
Adverse Events (AEs) of Interest During the Withdrawal Period Local injection site reactions(prespecified)	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days

Population: Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period. Treatment groups represent Treatment received during Treatment Period.

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. AEs of special interest are events potentially associated with the drug or disease under study. Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period. Treatment groups represent Treatment received during Treatment Period.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=55 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=48 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=43 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Adverse Events (AEs) of Interest During the Re-exposure Period Infections	17 participants	8 participants	12 participants
Adverse Events (AEs) of Interest During the Re-exposure Period Malignancy	0 participants	0 participants	0 participants
Adverse Events (AEs) of Interest During the Re-exposure Period Autoimmune Disorders (prespecified)	0 participants	0 participants	0 participants
Adverse Events (AEs) of Interest During the Re-exposure Period Local Injection site reactions (prespecified)	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Last dose in TP + 57 days, up to Month 24

Population: All randomized participants who received at least 1 dose of study drug in the Treatment Period, entered the Withdrawal Period, and had values available. n=number evaluable

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: Platelet count (\*10\^9 c/µL) \<0.67\*LLN or \>1.5\*ULN, or if preRX\<LLN, use 0.5\*preRX and \<100,000/mm\^3; potassium, serum (mEq) \<0.9\*LLN or \>1.1\*ULN, or if preRX \<LLN, use \<0.9\*preRX or \>ULN if preRX\>ULN, use \>1.1\*preRX or \<LLN; blood urea nitrogen (mg/dL) \>2\*preRX; creatinine (mg/dL) \>1.5\*preRX; ALT (U/L) \>3\*ULN, or if preRX\>ULN, use \>4\*preRX; AST (U/L) \>3\*ULN, or if preRX\>ULN, use \>4\*preRX; ALP (U/L) \>2\*ULN, or if preRX\>ULN, use \>3\*preRX; G-glutamyl transferase (GGT) (U/L) \>2\*ULN, or if preRX\>ULN, use \>3\*preRX; glucose, fasting (mg/dL) \<0.8\*LLN or \>1.5\*ULN, or if preRX\<LLN use \<0.8\*preRX or \>ULN if preRX \>ULN, use \>2.0\*preRX or OR \<LLN; glucose, serum (mg/dL) \<65 or \>220; uric acid (mg/dL)\>1.5\*ULN, or if preRX, use \>2\*preRX; albumin (g/dL) \<0.9\*LLN, or if preRX\<LLN, use \<0.75\*preRX; hemoglobin (g/dL)\>3 decrease from preRX; hematocrit (%) \< 0.75\*preRX.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=60 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=52 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=48 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period Hemoglobin Low (n=60, 52, 48)	1 participants	2 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period Creatinine High (n=60, 52, 48)	1 participants	2 participants	2 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period Alanine aminotransferase (ALT) High (n=60, 52, 48)	1 participants	0 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period GGT High (n=60, 52, 48)	1 participants	0 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period Fasting Glucose High (30, 28, 25)	0 participants	2 participants	1 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period Glucose Low (n=36,31,27)	5 participants	3 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period Glucose High (n=36, 31, 27)	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Start of re-exposure period to 56 days post last dose, up to Month 30

Population: All treated participants entering the Re-exposure Period and having measurements available were analyzed. n=evaluable. Treatment groups represent Treatment received during Treatment Period.

LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Criteria for marked abnormality on laboratory test results: Platelet count (\*10\^9 c/µL) \<0.67\*LLN or \>1.5\*ULN, or if preRX\<LLN, use 0.5\*preRX and \<100,000/mm\^3; potassium, serum (mEq) \<0.9\*LLN or \>1.1\*ULN, or if preRX \<LLN, use \<0.9\*preRX or \>ULN if preRX\>ULN, use \>1.1\*preRX or \<LLN; blood urea nitrogen (mg/dL) \>2\*preRX; creatinine (mg/dL) \>1.5\*preRX; ALT (U/L) \>3\*ULN, or if preRX\>ULN, use \>4\*preRX; AST (U/L) \>3\*ULN, or if preRX\>ULN, use \>4\*preRX; ALP (U/L) \>2\*ULN, or if preRX\>ULN, use \>3\*preRX; G-glutamyl transferase U/L) \>2\*ULN, or if preRX\>ULN, use \>3\*preRX; glucose, fasting (mg/dL) \<0.8\*LLN or \>1.5\*ULN, or if preRX\<LLN use \<0.8\*preRX or \>ULN if preRX \>ULN, use \>2.0\*preRX or OR \<LLN; glucose, serum (mg/dL) \<65 or \>220; uric acid (mg/dL)\>1.5\*ULN, or if preRX, use \>2\*preRX; albumin (g/dL) \<0.9\*LLN, or if preRX\<LLN, use \<0.75\*preRX; hemoglobin (g/dL)\>3 decrease from preRX; hematocrit (%) \< 0.75\*preRX.

Outcome measures

Outcome measures
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=55 Participants Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=48 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=43 Participants Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period Hematocrit Low (n=55,47,43)	0 participants	1 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period Hemoglobin Low (n=55,48, 43)	0 participants	2 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period Creatinine High (n=55, 48, 43)	0 participants	1 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period ALT High (n=55, 48, 43)	2 participants	0 participants	2 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period ALP High (n=55, 48, 43)	1 participants	0 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period AST High (n=55, 48, 43)	2 participants	0 participants	1 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period GGT High (n=55, 48, 43)	2 participants	0 participants	1 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period Fasting Glucose Low (n=33, 32, 28)	1 participants	0 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period Fasting Glucose High (n=33, 32, 28)	0 participants	2 participants	1 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period Glucose Low (n=27,24,18)	0 participants	2 participants	0 participants
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period Glucose High (n=27,24,18)	0 participants	0 participants	0 participants

Adverse Events

Abatacept, 125 mg, Plus Methotrexate, 2.5 mg

Serious events: 11 serious events

Other events: 81 other events

Deaths: 0 deaths

Abatacept, 125 mg, Plus Methotrexate Placebo

Serious events: 15 serious events

Other events: 64 other events

Deaths: 0 deaths

Methotrexate, 2.5 mg, Plus Abatacept Placebo

Serious events: 15 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 participants at risk Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC 125 mg/week and MTX. Safety data was collected from Day 1 to 56 days post last dose.	Abatacept, 125 mg, Plus Methotrexate Placebo n=116 participants at risk Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. Safety data was collected from Day 1 to 56 days post last dose.	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 participants at risk Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. Safety data was collected from Day 1 to 56 days post last dose.
Nervous system disorders Carotid artery occlusion	0.00% 0/119	0.86% 1/116	0.00% 0/116
Hepatobiliary disorders Cholelithiasis	0.00% 0/119	0.00% 0/116	0.86% 1/116
Reproductive system and breast disorders Endometrial disorder	0.00% 0/119	0.86% 1/116	0.00% 0/116
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/119	0.00% 0/116	0.86% 1/116
Infections and infestations Urinary tract infection	0.00% 0/119	0.00% 0/116	0.86% 1/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/119	0.00% 0/116	0.86% 1/116
Musculoskeletal and connective tissue disorders Osteoarthritis	0.84% 1/119	0.00% 0/116	0.00% 0/116
Injury, poisoning and procedural complications Post procedural complication	0.84% 1/119	0.00% 0/116	0.00% 0/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/119	0.00% 0/116	0.86% 1/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/119	0.86% 1/116	0.00% 0/116
Hepatobiliary disorders Cholangitis	0.84% 1/119	0.00% 0/116	0.00% 0/116
Psychiatric disorders Depression	0.00% 0/119	0.86% 1/116	0.00% 0/116
Investigations Hepatic enzyme increased	0.84% 1/119	0.00% 0/116	0.86% 1/116
Cardiac disorders Myocardial infarction	0.00% 0/119	0.86% 1/116	0.00% 0/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.84% 1/119	0.00% 0/116	0.00% 0/116
Nervous system disorders Sciatica	0.00% 0/119	0.86% 1/116	0.86% 1/116
Injury, poisoning and procedural complications Hand fracture	0.00% 0/119	0.86% 1/116	0.00% 0/116
Gastrointestinal disorders Incarcerated inguinal hernia	0.00% 0/119	0.00% 0/116	0.86% 1/116
Renal and urinary disorders Renal failure	0.00% 0/119	0.00% 0/116	0.86% 1/116
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/119	0.00% 0/116	0.86% 1/116
Investigations Transaminases increased	0.84% 1/119	0.00% 0/116	0.00% 0/116
Hepatobiliary disorders Cholecystitis	0.84% 1/119	0.00% 0/116	0.86% 1/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.00% 0/119	0.00% 0/116	0.86% 1/116
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/119	0.00% 0/116	0.86% 1/116
Injury, poisoning and procedural complications Tendon rupture	0.84% 1/119	0.00% 0/116	0.00% 0/116
Blood and lymphatic system disorders Anaemia	0.00% 0/119	0.86% 1/116	0.00% 0/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.84% 1/119	0.00% 0/116	0.00% 0/116
Infections and infestations Herpes zoster	0.00% 0/119	0.86% 1/116	0.00% 0/116
Injury, poisoning and procedural complications Overdose	2.5% 3/119	0.86% 1/116	1.7% 2/116
General disorders Strangulated hernia	0.00% 0/119	0.86% 1/116	0.00% 0/116
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/119	0.00% 0/116	0.86% 1/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour pulmonary	0.00% 0/119	0.86% 1/116	0.00% 0/116
Infections and infestations Pneumonia	0.84% 1/119	0.86% 1/116	0.00% 0/116
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/119	0.00% 0/116	0.86% 1/116
Infections and infestations Viral infection	0.00% 0/119	0.86% 1/116	0.00% 0/116
Infections and infestations Abscess limb	0.00% 0/119	0.86% 1/116	0.00% 0/116
Respiratory, thoracic and mediastinal disorders Emphysema	0.00% 0/119	0.86% 1/116	0.00% 0/116
Cardiac disorders Myocarditis post infection	0.00% 0/119	0.86% 1/116	0.00% 0/116
Blood and lymphatic system disorders Pancytopenia	0.84% 1/119	0.00% 0/116	0.00% 0/116
Infections and infestations Pyelonephritis	0.00% 0/119	0.00% 0/116	0.86% 1/116
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine neoplasm	0.00% 0/119	0.00% 0/116	0.86% 1/116

Other adverse events

Other adverse events
Measure	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg n=119 participants at risk Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC 125 mg/week and MTX. Safety data was collected from Day 1 to 56 days post last dose.	Abatacept, 125 mg, Plus Methotrexate Placebo n=116 participants at risk Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. Safety data was collected from Day 1 to 56 days post last dose.	Methotrexate, 2.5 mg, Plus Abatacept Placebo n=116 participants at risk Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period. Participants with a LDAS defined as DAS28-CRP score of \< 3.2 at Month 12 (end of Treatment Period) entered the Withdrawal Period for up to 12 months, during which all study medication was withdrawn. Participants with a DAS28-CRP score of \>3.2 were discontinued from the study. All MTX and corticosteroids, if not already discontinued, were to be tapered off during the first month of the Withdrawal Period. Participants who experienced a worsening of RA symptoms or a RA flare after at least 3 months in the Withdrawal Period were eligible to enroll into a 6-month Re-exposure Period, during which they received open-label treatment with abatacept SC (125 mg/week) and MTX. Safety data was collected from Day 1 to 56 days post last dose.
Nervous system disorders Headache	6.7% 8/119	6.9% 8/116	6.0% 7/116
Infections and infestations Pharyngitis	2.5% 3/119	5.2% 6/116	6.0% 7/116
Infections and infestations Urinary tract infection	11.8% 14/119	12.9% 15/116	12.9% 15/116
Gastrointestinal disorders Gastritis	3.4% 4/119	0.86% 1/116	6.0% 7/116
Gastrointestinal disorders Nausea	15.1% 18/119	6.9% 8/116	13.8% 16/116
Respiratory, thoracic and mediastinal disorders Cough	3.4% 4/119	7.8% 9/116	6.0% 7/116
Gastrointestinal disorders Mouth ulceration	5.0% 6/119	4.3% 5/116	1.7% 2/116
Gastrointestinal disorders Gastrooesophageal reflux disease	5.0% 6/119	0.86% 1/116	0.86% 1/116
Vascular disorders Hypertension	3.4% 4/119	1.7% 2/116	5.2% 6/116
Gastrointestinal disorders Diarrhoea	4.2% 5/119	6.9% 8/116	3.4% 4/116
Infections and infestations Influenza	4.2% 5/119	7.8% 9/116	5.2% 6/116
Infections and infestations Sinusitis	7.6% 9/119	3.4% 4/116	1.7% 2/116
Infections and infestations Gastroenteritis	5.0% 6/119	2.6% 3/116	6.9% 8/116
Infections and infestations Nasopharyngitis	23.5% 28/119	17.2% 20/116	19.0% 22/116
Gastrointestinal disorders Abdominal pain upper	4.2% 5/119	5.2% 6/116	5.2% 6/116
Infections and infestations Bronchitis	6.7% 8/119	5.2% 6/116	8.6% 10/116
Infections and infestations Upper respiratory tract infection	12.6% 15/119	12.9% 15/116	17.2% 20/116
Gastrointestinal disorders Vomiting	5.0% 6/119	2.6% 3/116	0.86% 1/116

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