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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01142726
• Collaborator: (none)
• Enrollment: 511
• Locations: 73
• Arms: 3
• Duration (Months): 46
• Patients Per Site: 7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary purpose of the protocol is to demonstrate the ability of abatacept plus methotrexate to induce remission in patients with very early rheumatoid arthritis after 12 months of treatment and to maintain remission following 6 months of drug withdrawal.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 511 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Randomized, Active Controlled Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate in Inducing Clinical Remission Compared to Methotrexate Monotherapy in Adults With Very Early RA
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Abatacept, 125 mg, plus methotrexate, 2.5 mg Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Drug: Abatacept; Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months; Other Names: Orencia BMS 188667 ; Drug: Methotrexate; Tablets, oral, 2.5 mg, once weekly, 12 months; Other Names: Rheumatrex
Active Comparator: 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	Drug: Methotrexate; Tablets, oral, 2.5 mg, once weekly, 12 months; Other Names: Rheumatrex ; Drug: Abatacept placebo; Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months
Active Comparator: 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	Drug: Abatacept; Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months; Other Names: Orencia BMS 188667 ; Drug: Methotrexate placebo; Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months

Outcome Measures

Primary Outcome Measures

1. 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 [Randomization to Months 12 and 18]

   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.)

Secondary Outcome Measures

1. 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 [Randomization to Months 12 and 18]

   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.)

2. Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population [Randomization to Month 24]

   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.)

3. Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18 [Baseline to Month 18]

   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.)

4. Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18 [Randomization to Month 18]

   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.

5. Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time [Randomization to Month 18]

   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)..

6. Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time [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.

7. Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time [Randomization to Month 18]

   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.

8. 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) [Randomization to Months 6, 12, and 18]

   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.

9. Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI) [Randomization to Month 18]

   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.

10. 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 [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]

    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. Related=having certain, probable, possible, or unknown relationship to study drug.

11. Adverse Events (AEs) of Interest During the Treatment Period [Day 1 to 56 days following last dosing day (Day 365)]

    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. Related=having certain, probable, possible, or unknown relationship to study drug. AEs of special interest are events potentially associated with the drug or disease under study.

12. Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period [Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)]

    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.

13. 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 [End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)]

    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)

14. Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period [Randomization to Month 24]

    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. Percent=number with remission/number evaluated (ITT)

15. Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods) [Day 1 to 56 days post last dose in the study, up to Month 30]

    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.

16. Adverse Events (AEs) of Interest During the Withdrawal Period [Last dose in TP + 57 days, up to Month 24]

    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.

17. Adverse Events (AEs) of Interest During the Re-exposure Period [First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days]

    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.

18. Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period [Last dose in TP + 57 days, up to Month 24]

    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.

19. Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period [Start of re-exposure period to 56 days post last dose, up to Month 30]

    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.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening

• Onset of persistent symptoms ≤ 2 years prior to screening

• Positive test result for anticyclic citrullinated peptides 2

• Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit

• Biologic naive, including no treatment with an investigational biologic prior to screening

• Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening

• Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization

• If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks

• Able to undergo magnetic resonance imaging

Key Exclusion Criteria:

• Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus)

• Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization

• Scheduled for or anticipating joint replacement surgery

• Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator

• History of malignancy in the last 5 years

• Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection

• At risk for tuberculosis

• Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheumatology Associates Of North Alabama, P.C.	Huntsville	Alabama	United States	35801
2	St. Joseph'S Mercy Clinic	Hot Springs	Arkansas	United States	71913
3	Sarasota Arthritis Research Center	Sarasota	Florida	United States	34239
4	Coeur D'Alene Arthrit Clin	Coeur D Alene	Idaho	United States	83814
5	Johns Hopkins University Division Of Rheumatology	Baltimore	Maryland	United States	21224
6	Clinical Pharmacology Study Group	Worcester	Massachusetts	United States	01605
7	Arthritis Associates Of Mississippi	Jackson	Mississippi	United States	39202
8	Physician Research Collaboration, Llc	Lincoln	Nebraska	United States	68516
9	Piedmont Rheumatology, Pa	Hickory	North Carolina	United States	28602
10	Carolina Arthritis Associates	Wilmington	North Carolina	United States	28401
11	Metrohealth Medical Center	Cleveland	Ohio	United States	44109
12	Isam A. Diab, Md	Middleburg	Ohio	United States	44130
13	Alan J. Kivitz, Md, Cpi	Duncansville	Pennsylvania	United States	16635
14	Mitchell C. Feinman, Md	Orangeburg	South Carolina	United States	29118
15	Kurt Oelke, Md	Glendale	Wisconsin	United States	53217
16	Local Institution	Cairns	Queensland	Australia	4870
17	Local Institution	Maroochydore	Queensland	Australia	4558
18	Local Institution	Woodville	South Australia	Australia	5011
19	Local Institution	Heidelberg	Victoria	Australia	3084
20	Local Institution	Malvern	Victoria	Australia	3144
21	Local Institution	Victoria Park	Western Australia	Australia	6100
22	Local Institution	Bruxelles		Belgium	1200
23	Local Institution	Kortrijk		Belgium	8500
24	Local Institution	Merksem		Belgium	2170
25	Local Institution	Calgary	Alberta	Canada	T2N 4N1
26	Local Institution	Laval	Quebec	Canada	H7T 2P5
27	Local Institution	Hjorring		Denmark	9800
28	Local Institution	Helsinki		Finland	00290
29	Local Institution	Tampere		Finland	33521
30	Local Institution	Chambray Les Tours		France	37170
31	Local Institution	Montpellier		France	34295
32	Local Institution	Paris Cedex 14		France	75679
33	Local Institution	Poitiers		France	86021
34	Local Institution	Berlin		Germany	10117
35	Local Institution	Berlin		Germany	14059
36	Local Institution	Hildesheim		Germany	31134
37	Local Institution	Muenchen		Germany	80336
38	Local Institution	Muenchen		Germany	80639
39	Local Institution	Muenchen		Germany	81541
40	Local Institution	Ancona		Italy	60055
41	Local Institution	Siena		Italy	53100
42	Local Institution	Daegu		Korea, Republic of	705-718
43	Local Institution	Daejeon		Korea, Republic of	302-799
44	Local Institution	Seoul		Korea, Republic of	133-791
45	Local Institution	Seoul		Korea, Republic of	137-701
46	Local Institution	Metepec	Estado De Mexico	Mexico	52140
47	Local Institution	Guadalajara	Jalisco	Mexico	44500
48	Local Institution	Guadalajara	Jalisco	Mexico	44690
49	Local Institution	Monterrey	Nuevo Leon	Mexico	64020
50	Local Institution	Merida	Yucatan	Mexico	97000
51	Local Institution	Chihuahua		Mexico	31000
52	Local Institution	Queretaro		Mexico	76178
53	Local Institution	San Luis Potosi		Mexico	78240
54	Local Institution	Lublin		Poland	20-954
55	Local Institution	Poznan		Poland	60-218
56	Local Institution	Torun		Poland	87100
57	Local Institution	Warszawa		Poland	01-157
58	Local Institution	Warszawa		Poland	01-868
59	Local Institution	Wroc#aw		Poland	50-088
60	Local Institution	Moscow		Russian Federation	117049
61	Local Institution	Moscow		Russian Federation	129327
62	Local Institution	Tver		Russian Federation	170036
63	Local Institution	Kempton Park	Gauteng	South Africa	1619
64	Local Institution	Pretoria	Gauteng	South Africa	0083
65	Local Institution	Pretoria	Gauteng	South Africa	0084
66	Local Institution	Pretoria	Gauteng	South Africa	0181
67	Local Institution	Durban	Kwa Zulu Natal	South Africa	4001
68	Local Institution	Panorama	Western Cape	South Africa	7500
69	Local Institution	Goteborg		Sweden	413 45
70	Local Institution	Linkoping		Sweden	581 85
71	Local Institution	Malmo		Sweden	205 02
72	Local Institution	Stockholm		Sweden	171 76
73	Local Institution	Uppsala		Sweden	751 85

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01142726
• Other Study ID Numbers: IM101-226; 2010-018674-20
• First Posted: Jun 11, 2010
• Last Update Posted: Jan 14, 2016
• Last Verified: Dec 1, 2015

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

Study Results

Participant Flow

Pre-assignment Detail	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).

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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.	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.	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.
Period Title: Treatment Phase: Day 1 Through Month 12
STARTED	119	116	116
COMPLETED	103	91	96
NOT COMPLETED	16	25	20
Period Title: Treatment Phase: Day 1 Through Month 12
STARTED	84	66	75
COMPLETED	14	10	17
NOT COMPLETED	70	56	58
Period Title: Treatment Phase: Day 1 Through Month 12
STARTED	55	48	43
COMPLETED	54	46	40
NOT COMPLETED	1	2	3

Baseline Characteristics

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo	Total
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period	Total of all reporting groups
Overall Participants	119	116	116	351
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.4 (13.20)	45.4 (11.92)	49.1 (12.36)	47.0 (12.57)
Sex: Female, Male (Count of Participants)
Female	95 79.8%	89 76.7%	89 76.7%	273 77.8%
Male	24 20.2%	27 23.3%	27 23.3%	78 22.2%
Race/Ethnicity, Customized (Number) [Number]
White	100 84%	95 81.9%	102 87.9%	297 84.6%
Asian	14 11.8%	13 11.2%	9 7.8%	36 10.3%
Black/African American	2 1.7%	4 3.4%	2 1.7%	8 2.3%
American Indian/Alaska native	1 0.8%	1 0.9%	1 0.9%	3 0.9%
Other	2 1.7%	3 2.6%	2 1.7%	7 2%
Duration of rheumatoid arthritis (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	0.58 (0.500)	0.59 (0.522)	0.50 (0.488)	0.56 (0.504)
Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	5.528 (1.2501)	5.463 (1.1493)	5.315 (1.3330)	5.435 (1.2465)
Health Assessment Questionnaire Disability Index (HAQ-DI) score (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	1.452 (0.6778)	1.419 (0.6587)	1.383 (0.6493)	1.419 (0.6609)
Rheumatoid factor status (Number) [Number]
Positive	113 95%	111 95.7%	110 94.8%	334 95.2%
Negative	6 5%	5 4.3%	6 5.2%	17 4.8%
Tender joint count (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	24.3 (15.74)	23.9 (14.47)	21.7 (14.00)	23.3 (14.77)
Swollen joint count (Joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Joints]	16.5 (12.43)	17.2 (12.88)	15.7 (11.78)	16.5 (12.35)

Outcome Measures

1. Primary Outcome

Title	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
Description	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.)
Time Frame	Randomization to Months 12 and 18

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116
Month 12 (TP Day 365) (n=115, 115)	60.9 51.2%	45.2 39%
Both Months 12 & 18 (WP Day 169) (n=115, 115)	14.8 12.4%	7.8 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg, Methotrexate, 2.5 mg, Plus Abatacept Placebo
	Comments	Power estimate assumed 2-sided alpha level of 5% and that 60% of abatacept (ABA)+methotrexate (MX) patients (pts) would be in DAS28-CRP remission at Month 12 compared with 38% of MX monotherapy pts. Also assumed that 48% of ABA monotherapy pts would be in DAS28-CRP remission at Month 12, yielding an expected treatment difference from MX of 10% in favor of ABA monotherapy; 116 pts randomized to ABA monotherapy would yield a half-length of the 95% CI around that 10% treatment difference of 13.5%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Regression, Logistic
	Comments	Statistical testing of the 2 coprimary efficacy endpoints was conducted in a hierarchical fashion to maintain the overall Type I error rate at 5%.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.01
	Confidence Interval	(2-Sided) 95%; 1.18 to 3.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.55
	Estimation Comments	At Month 12

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg, Methotrexate, 2.5 mg, Plus Abatacept Placebo
	Comments	Conditional on statistical significance of the 1st coprimary efficacy analysis (CEA), a sample of 116 patients per arm would provide 98% power for the 2nd CEA comparison of the percentage of patients in DAS28-CRP remission at Months 12 and 18 between the abatacept (ABA)+methotrexate (MTX) arm and the MTX monotherapy arm for intent-to treat population. This sample size calculation assumed 30% remission in the ABA+MTX arm and 8% in the monotherapy arm at Month 18 and a 2-sided alpha level of 5%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.045
	Comments
	Method	Regression, Logistic
	Comments	Statistical testing of the 2 coprimary efficacy endpoints was conducted in a hierarchical fashion to maintain the overall Type I error rate at 5%.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.51
	Confidence Interval	(2-Sided) 95%; 1.02 to 6.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.15
	Estimation Comments	At Months 12 and 18

2. Secondary Outcome

Title	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
Description	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.)
Time Frame	Randomization to Months 12 and 18

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	116	116
At Month 12 (TP Day 365) (n=113, 115)	42.5 35.7%	45.2 39%
At both Months 12 &18 (WP Day 169) (n=113, 115)	12.4 10.4%	7.8 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg, Methotrexate, 2.5 mg, Plus Abatacept Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments	At Month 12

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg, Methotrexate, 2.5 mg, Plus Abatacept Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.04
	Confidence Interval	(2-Sided) 95%; 0.81 to 5.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.96
	Estimation Comments	At Months 12 and 18

3. Secondary Outcome

Title	Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population
Description	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.)
Time Frame	Randomization to Month 24

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116	116
TP Day 29	13.4 11.3%	8.6 7.4%	6.0 5.2%
TP Day 57	24.4 20.5%	11.2 9.7%	9.5 8.2%
TP Day 85	36.1 30.3%	21.6 18.6%	17.2 14.8%
TP Day 113	37.8 31.8%	29.3 25.3%	19.0 16.4%
TP Day 141	45.4 38.2%	29.3 25.3%	25.0 21.6%
TP Day 169	45.4 38.2%	32.8 28.3%	26.7 23%
TP Day 197	52.1 43.8%	36.2 31.2%	25.9 22.3%
TP Day 225	57.1 48%	40.5 34.9%	30.2 26%
TP Day 253	62.2 52.3%	37.9 32.7%	30.2 26%
TP 281	51.3 43.1%	42.2 36.4%	32.8 28.3%
TP 309	56.3 47.3%	37.9 32.7%	36.2 31.2%
TP Day 337	63.0 52.9%	43.1 37.2%	33.6 29%
TP 365	61.3 51.5%	43.1 37.2%	45.7 39.4%
WP Day 29	51.3 43.1%	36.2 31.2%	27.6 23.8%
WP Day 57	40.3 33.9%	25.0 21.6%	18.1 15.6%
WP Day 85	31.1 26.1%	18.1 15.6%	18.1 15.6%
WP Day 169	19.3 16.2%	12.9 11.1%	9.5 8.2%
WP Day 253	17.6 14.8%	9.5 8.2%	13.8 11.9%
WP Day 365	9.2 7.7%	6.0 5.2%	6.0 5.2%

4. Secondary Outcome

Title	Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18
Description	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.)
Time Frame	Baseline to Month 18

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116	116
Month 6 (TP Day 169) (n=102, 96, 101)	-2.72 (0.12)	-2.33 (0.12)	-1.93 (0.12)
Month 12 (TP Day 365) (n=95, 84, 91)	-3.09 (0.13)	-2.75 (0.13)	-2.58 (0.13)
Month 18 (WP Day 169) (n=41, 31, 32)	-1.54 (0.26)	-1.51 (0.29)	-1.06 (0.29)

5. Secondary Outcome

Title	Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18
Description	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.
Time Frame	Randomization to Month 18

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116	116
Month 12 (TP Day 365)	42.0 35.3%	29.3 25.3%	25.0 21.6%
Month 18 (WP Day 169)	10.9 9.2%	8.6 7.4%	6.9 5.9%

6. Secondary Outcome

Title	Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time
Description	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)..
Time Frame	Randomization to Month 18

Outcome Measure Data

Analysis Population Description

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

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

7. Secondary Outcome

Title	Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time
Description	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.
Time Frame	Randomization to Month 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116	116
TP Day 29	42.0 35.3%	31.0 26.7%	21.6 18.6%
TP Day 57	55.5 46.6%	44.0 37.9%	37.9 32.7%
TP Day 85	63.0 52.9%	45.7 39.4%	41.4 35.7%
TP Day 113	63.0 52.9%	49.1 42.3%	45.7 39.4%
TP Day 141	62.2 52.3%	51.7 44.6%	44.0 37.9%
TP Day 169	63.9 53.7%	56.0 48.3%	41.4 35.7%
TP Day 197	66.4 55.8%	59.5 51.3%	41.4 35.7%
TP Day 225	66.4 55.8%	57.8 49.8%	38.8 33.4%
TP Day 253	68.9 57.9%	55.2 47.6%	45.7 39.4%
TP Day 281	64.7 54.4%	56.9 49.1%	46.6 40.2%
TP Day 309	65.5 55%	56.9 49.1%	46.6 40.2%
TP Day 337	64.7 54.4%	55.2 47.6%	46.6 40.2%
TP Day 365	67.2 56.5%	52.6 45.3%	44.0 37.9%
WP Day 29	52.1 43.8%	39.7 34.2%	37.1 32%
WP Day 57	43.7 36.7%	34.5 29.7%	26.7 23%
WP Day 85	39.5 33.2%	28.4 24.5%	23.3 20.1%
WP Day 169	22.7 19.1%	16.4 14.1%	10.3 8.9%
WP Day 253	15.1 12.7%	9.5 8.2%	6.9 5.9%
WP Day 365	10.1 8.5%	6.9 5.9%	5.2 4.5%

8. Secondary Outcome

Title	Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time
Description	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.
Time Frame	Randomization to Month 18

Outcome Measure Data

Analysis Population Description

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

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

9. Secondary Outcome

Title	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)
Description	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.
Time Frame	Randomization to Months 6, 12, and 18

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months Methotrexate placebo: Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months Abatacept placebo: Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months
Measure Participants	119	116	116
PCS score TP Day 169 (n=106, 95, 96)	11.68 (0.82)	9.16 (0.86)	7.47 (0.85)
PCS score TP Day 365 (n=94, 88, 91)	13.91 (0.93)	10.23 (0.97)	10.92 (0.95)
PCS score WP Day 169 (n=48, 36, 37)	6.16 (1.45)	4.59 (1.65)	6.27 (1.63)
MCS score TP Day 169 (n=106, 95, 96)	6.11 (0.92)	3.99 (0.97)	4.69 (0.95)
MCS score TP Day 365 (n=94, 88, 91)	7.67 (1.04)	5.48 (1.08)	7.23 (1.06)
MCS score WP Day 169 (n=48, 36, 37)	2.75 (1.44)	4.36 (1.64)	2.23 (1.63)

10. Secondary Outcome

Title	Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	Randomization to Month 18

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period Abatacept: Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months Methotrexate placebo: Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period Methotrexate: Tablets, oral, 2.5 mg, once weekly, 12 months Abatacept placebo: Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months
Measure Participants	119	116	116
Osteitis TP Day 169 (n=93, 94, 89)	-2.03 (0.47)	-1.13 (0.47)	-0.73 (0.48)
Osteitis TP Day 365 (n=83, 74, 78)	-2.32 (0.46)	-1.30 (0.46)	-0.90 (0.46)
Osteitis WP Day 169 (n=31, 30, 25)	-1.94 (0.88)	0.98 (0.89)	-0.33 (0.96)
Erosion TP Day 169 (n=93, 94, 89)	0.26 (0.28)	1.15 (0.28)	1.15 (0.28)
Erosion TP Day 365 (n=83, 74, 78)	0.34 (0.35)	1.57 (0.36)	1.56 (0.36)
Erosion WP Day 169 (n=31, 30, 25)	0.20 (0.47)	2.16 (0.48)	1.89 (0.50)
Synovitis TP Day 169 (n=93, 94, 89)	-1.82 (0.21)	-0.93 (0.21)	-0.78 (0.21)
Synovitis TP Day 365 (n=83, 74, 78)	-2.38 (0.29)	-1.36 (0.30)	-0.77 (0.30)
Synovitis WP Day 169 (n=31, 30, 25))	-1.71 (0.45)	-0.95 (0.45)	-0.71 (0.49)

11. Secondary Outcome

Title	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
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116	116
Deaths	0 0%	0 0%	2 1.7%
SAEs	8 6.7%	14 12.1%	9 7.8%
Related SAEs	3 2.5%	3 2.6%	1 0.9%
Discontinuations due to SAEs	2 1.7%	5 4.3%	3 2.6%
Related AEs	53 44.5%	48 41.4%	51 44%
Discontinuations due to AEs	4 3.4%	8 6.9%	5 4.3%

12. Secondary Outcome

Title	Adverse Events (AEs) of Interest During the Treatment Period
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. AEs of special interest are events potentially associated with the drug or disease under study.
Time Frame	Day 1 to 56 days following last dosing day (Day 365)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116	116
Infections	68 57.1%	64 55.2%	69 59.5%
Malignancy	1 0.8%	2 1.7%	1 0.9%
Autoimmune disorders (prespecified)	1 0.8%	2 1.7%	3 2.6%
Local injection site reactions (prespecified)	2 1.7%	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period
Description	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.
Time Frame	Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period	Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period	Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
Measure Participants	119	116	116
Platelet count (high) (n=119, 116, 115)	2 1.7%	0 0%	0 0%
Potassium, serum (low)	1 0.8%	1 0.9%	1 0.9%
Blood urea nitrogen (high)	4 3.4%	1 0.9%	2 1.7%
Creatinine (high)	2 1.7%	1 0.9%	3 2.6%
Alanine aminotransferase (ALT)(high)	3 2.5%	0 0%	2 1.7%
Aspartate aminotransferase (AST)(high)	2 1.7%	0 0%	1 0.9%
G-glutamyl transferase (GGT) (high)	3 2.5%	1 0.9%	1 0.9%
Glucose, fasting (low) (n=78, 72, 75)	2 1.7%	0 0%	2 1.7%
Glucose, fasting (high) (n=78, 72, 75)	1 0.8%	2 1.7%	1 0.9%
Glucose, serum (low) (n=84, 78, 75)	5 4.2%	6 5.2%	2 1.7%
Glucose, serum (high) (n=84, 78, 75)	1 0.8%	4 3.4%	3 2.6%
Uric acid (high)	0 0%	1 0.9%	0 0%
Albumin (low)	1 0.8%	1 0.9%	4 3.4%
Hemoglobin (low) (n=119, 116, 115)	0 0%	2 1.7%	0 0%
Hematocrit (low) (n=119, 116, 115)	0 0%	2 1.7%	0 0%

14. Secondary Outcome

Title	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
Description	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)
Time Frame	End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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 SC (125 mg/week) and MTX.	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.	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.
Measure Participants	73	50	53
WP Day 29	73.3 61.6%	72.0 62.1%	54.7 47.2%
WP Day 57	58.9 49.5%	56.0 48.3%	32.1 27.7%
WP Day 85	42.5 35.7%	40.0 34.5%	35.8 30.9%
WP Day 169	26.0 21.8%	30.0 25.9%	17.0 14.7%
WP Day 253	20.5 17.2%	22.0 19%	20.8 17.9%
WP Day 365	12.3 10.3%	14.0 12.1%	11.3 9.7%

15. Secondary Outcome

Title	Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period
Description	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. Percent=number with remission/number evaluated (ITT)
Time Frame	Randomization to Month 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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 SC (125 mg/week) and MTX.	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.	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.
Measure Participants	119	116	116
TP Day 29	4.2 3.5%	3.4 2.9%	1.7 1.5%
TP Day 57	9.2 7.7%	6.0 5.2%	1.7 1.5%
TP Day 85	17.6 14.8%	8.6 7.4%	6.0 5.2%
TP Day 113	23.5 19.7%	17.2 14.8%	7.8 6.7%
TP Day 141	31.9 26.8%	23.3 20.1%	10.3 8.9%
TP Day 169	31.1 26.1%	20.7 17.8%	11.2 9.7%
TP Day 197	33.6 28.2%	21.6 18.6%	12.9 11.1%
TP Day 225	38.7 32.5%	25.9 22.3%	14.7 12.7%
TP Day 253	37.8 31.8%	25.0 21.6%	13.8 11.9%
TP Day 281	37.8 31.8%	26.7 23%	18.1 15.6%
TP Day 309	40.3 33.9%	26.7 23%	19.0 16.4%
TP Day 337	41.2 34.6%	31.0 26.7%	19.0 16.4%
TP Day 365	42.0 35.3%	29.3 25.3%	25.0 21.6%
WP Day 29	38.7 32.5%	26.7 23%	14.7 12.7%
WP Day 57	26.9 22.6%	20.7 17.8%	10.3 8.9%
WP Day 85	21.0 17.6%	15.5 13.4%	14.7 12.7%
WP Day 169	11.8 9.9%	9.5 8.2%	6.9 5.9%
WP Day 253	11.8 9.9%	9.5 8.2%	7.8 6.7%
WP Day 365	6.7 5.6%	4.3 3.7%	4.3 3.7%

16. Secondary Outcome

Title	Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. 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.
Time Frame	Day 1 to 56 days post last dose in the study, up to Month 30

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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 SC (125 mg/week) and MTX.	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.	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.
Measure Participants	119	116	116
Death	0 0%	0 0%	2 1.7%
SAE	11 9.2%	15 12.9%	15 12.9%
Discontinued Due to AE	4 3.4%	8 6.9%	7 6%

17. Secondary Outcome

Title	Adverse Events (AEs) of Interest During the Withdrawal Period
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. 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.
Time Frame	Last dose in TP + 57 days, up to Month 24

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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 SC (125 mg/week) and MTX.	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.	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.
Measure Participants	84	66	75
Infections	8 6.7%	6 5.2%	10 8.6%
Malignancy	1 0.8%	0 0%	1 0.9%
Autoimmune disorders (prespecified)	0 0%	0 0%	1 0.9%
Local injection site reactions(prespecified)	0 0%	0 0%	0 0%

18. Secondary Outcome

Title	Adverse Events (AEs) of Interest During the Re-exposure Period
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. 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.
Time Frame	First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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 SC (125 mg/week) and MTX.	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.	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.
Measure Participants	55	48	43
Infections	17 14.3%	8 6.9%	12 10.3%
Malignancy	0 0%	0 0%	0 0%
Autoimmune Disorders (prespecified)	0 0%	0 0%	0 0%
Local Injection site reactions (prespecified)	0 0%	0 0%	0 0%

19. Secondary Outcome

Title	Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period
Description	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.
Time Frame	Last dose in TP + 57 days, up to Month 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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 SC (125 mg/week) and MTX.	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.	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.
Measure Participants	60	52	48
Hemoglobin Low (n=60, 52, 48)	1 0.8%	2 1.7%	0 0%
Creatinine High (n=60, 52, 48)	1 0.8%	2 1.7%	2 1.7%
Alanine aminotransferase (ALT) High (n=60, 52, 48)	1 0.8%	0 0%	0 0%
GGT High (n=60, 52, 48)	1 0.8%	0 0%	0 0%
Fasting Glucose High (30, 28, 25)	0 0%	2 1.7%	1 0.9%
Glucose Low (n=36,31,27)	5 4.2%	3 2.6%	0 0%
Glucose High (n=36, 31, 27)	0 0%	1 0.9%	1 0.9%

20. Secondary Outcome

Title	Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period
Description	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.
Time Frame	Start of re-exposure period to 56 days post last dose, up to Month 30

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg	Abatacept, 125 mg, Plus Methotrexate Placebo	Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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 SC (125 mg/week) and MTX.	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.	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.
Measure Participants	55	48	43
Hematocrit Low (n=55,47,43)	0 0%	1 0.9%	0 0%
Hemoglobin Low (n=55,48, 43)	0 0%	2 1.7%	0 0%
Creatinine High (n=55, 48, 43)	0 0%	1 0.9%	0 0%
ALT High (n=55, 48, 43)	2 1.7%	0 0%	2 1.7%
ALP High (n=55, 48, 43)	1 0.8%	0 0%	0 0%
AST High (n=55, 48, 43)	2 1.7%	0 0%	1 0.9%
GGT High (n=55, 48, 43)	2 1.7%	0 0%	1 0.9%
Fasting Glucose Low (n=33, 32, 28)	1 0.8%	0 0%	0 0%
Fasting Glucose High (n=33, 32, 28)	0 0%	2 1.7%	1 0.9%
Glucose Low (n=27,24,18)	0 0%	2 1.7%	0 0%
Glucose High (n=27,24,18)	0 0%	0 0%	0 0%

Adverse Events

Arm/Group Title	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg		Abatacept, 125 mg, Plus Methotrexate Placebo		Methotrexate, 2.5 mg, Plus Abatacept Placebo
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg		Abatacept, 125 mg, Plus Methotrexate Placebo		Methotrexate, 2.5 mg, Plus Abatacept Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg		Abatacept, 125 mg, Plus Methotrexate Placebo		Methotrexate, 2.5 mg, Plus Abatacept Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/119 (9.2%)		15/116 (12.9%)		15/116 (12.9%)
Blood and lymphatic system disorders
Anaemia	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Pancytopenia	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Cardiac disorders
Myocardial infarction	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Myocarditis post infection	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Gastrointestinal disorders
Small intestinal obstruction	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Incarcerated inguinal hernia	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
General disorders
Strangulated hernia	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Hepatobiliary disorders
Cholelithiasis	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Cholangitis	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Cholecystitis	1/119 (0.8%)		0/116 (0%)		1/116 (0.9%)
Infections and infestations
Urinary tract infection	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Herpes zoster	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Pneumonia	1/119 (0.8%)		1/116 (0.9%)		0/116 (0%)
Viral infection	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Abscess limb	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Pyelonephritis	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Injury, poisoning and procedural complications
Post procedural complication	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Hand fracture	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Tendon rupture	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Overdose	3/119 (2.5%)		1/116 (0.9%)		2/116 (1.7%)
Investigations
Hepatic enzyme increased	1/119 (0.8%)		0/116 (0%)		1/116 (0.9%)
Transaminases increased	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Rheumatoid arthritis	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Foot deformity	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Bursitis	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Uterine cancer	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Bowen's disease	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Prostate cancer	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Colon adenoma	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Basal cell carcinoma	1/119 (0.8%)		0/116 (0%)		0/116 (0%)
Carcinoid tumour pulmonary	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Uterine neoplasm	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Nervous system disorders
Carotid artery occlusion	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Sciatica	0/119 (0%)		1/116 (0.9%)		1/116 (0.9%)
Psychiatric disorders
Depression	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Renal and urinary disorders
Renal failure	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Reproductive system and breast disorders
Endometrial disorder	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/119 (0%)		0/116 (0%)		1/116 (0.9%)
Emphysema	0/119 (0%)		1/116 (0.9%)		0/116 (0%)
Other (Not Including Serious) Adverse Events
	Abatacept, 125 mg, Plus Methotrexate, 2.5 mg		Abatacept, 125 mg, Plus Methotrexate Placebo		Methotrexate, 2.5 mg, Plus Abatacept Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/119 (68.1%)		64/116 (55.2%)		78/116 (67.2%)
Gastrointestinal disorders
Gastritis	4/119 (3.4%)		1/116 (0.9%)		7/116 (6%)
Nausea	18/119 (15.1%)		8/116 (6.9%)		16/116 (13.8%)
Mouth ulceration	6/119 (5%)		5/116 (4.3%)		2/116 (1.7%)
Gastrooesophageal reflux disease	6/119 (5%)		1/116 (0.9%)		1/116 (0.9%)
Diarrhoea	5/119 (4.2%)		8/116 (6.9%)		4/116 (3.4%)
Abdominal pain upper	5/119 (4.2%)		6/116 (5.2%)		6/116 (5.2%)
Vomiting	6/119 (5%)		3/116 (2.6%)		1/116 (0.9%)
Infections and infestations
Pharyngitis	3/119 (2.5%)		6/116 (5.2%)		7/116 (6%)
Urinary tract infection	14/119 (11.8%)		15/116 (12.9%)		15/116 (12.9%)
Influenza	5/119 (4.2%)		9/116 (7.8%)		6/116 (5.2%)
Sinusitis	9/119 (7.6%)		4/116 (3.4%)		2/116 (1.7%)
Gastroenteritis	6/119 (5%)		3/116 (2.6%)		8/116 (6.9%)
Nasopharyngitis	28/119 (23.5%)		20/116 (17.2%)		22/116 (19%)
Bronchitis	8/119 (6.7%)		6/116 (5.2%)		10/116 (8.6%)
Upper respiratory tract infection	15/119 (12.6%)		15/116 (12.9%)		20/116 (17.2%)
Nervous system disorders
Headache	8/119 (6.7%)		8/116 (6.9%)		7/116 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	4/119 (3.4%)		9/116 (7.8%)		7/116 (6%)
Vascular disorders
Hypertension	4/119 (3.4%)		2/116 (1.7%)		6/116 (5.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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