Abatacept Versus Adalimumab Head-to-Head

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00929864
• Collaborator: (none)
• Enrollment: 869
• Locations: 84
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is demonstrate that subcutaneous abatacept is non-inferior (no worse than) to subcutaneous adalimumab in the treatment of subjects with rheumatoid arthritis who are biologic naive

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 869 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Head-to-Head, Single-Blind Study to Compare the Efficacy and Safety of Subcutaneous Abatacept Versus Subcutaneous Adalimumab, Both With Background Methotrexate, in Biologic-Naive Subjects With Rheumatoid Arthritis
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Abatacept	Drug: Abatacept; Syringes, Subcutaneous, 125 mg/syringe for Subcutaneous, Weekly Subcutaneous injections, 24 months (729 days); Other Names: Orencia BMS-188667
Active Comparator: Adalimumab	Drug: Adalimumab; Syringes, Subcutaneous, 40 mg, Biweekly Subcutaneous injections, 24 months (729 days); Other Names: Humira

Outcome Measures

Primary Outcome Measures

1. The Proportion of Participants Meeting the American College of Rheumatology (ACR) Criteria of 20% Improvement (ACR20) After 12 Months of Treatment - Intent to Treat Population [Day 1 to Day 365]

   Proportion(%)=number of participants meeting criteria (n) divided by number of participants who received drug (N). The ACR score indicates degree of improvement in a patient's rheumatoid arthritis (RA), based on guidelines set forth by the ACR and represents a percentage. To qualify a ACR20 score, patient must have >=20% fewer tender joints and >=20% fewer swollen joints and show 20% improvement from baseline in at least 3 of: patient overall assessment of his/her RA, physician global assessment of the patient's RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein (CRP) test (to assess inflammation). Baseline was Day 1. Randomization was stratified using screening Disease Activity Score-28 (DAS28) CRP, a composite of 4 variables: number of tender joints/28, number of swollen joints/28, CRP in mg/L and participant assessment of disease activity with visual analogue scale.

Secondary Outcome Measures

1. Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population [Day 1 to 12 Months]

   n=number of participants with a pre-specified local injection site reaction event, N=number of participants at risk. Proportion (%) = n/N. 12 Months includes data up to 56 days post last dose of the first 12 months Period or start of the first dose of second 12 months period.

2. Incidence Rate of Local Injection Site Reactions (Pre-specified) Reported During 24 Month Period - ITT Population [Day 1 to Day 729]

   Incidence Rate: (incidence/100 person-years) = number of participants with event * 100 /exposure (person-years) Exposure (person-years) = the sum over all participants of the exposure per participant in the 24 months (censored at the time of first occurrence of AE) expressed in days, divided by 365.25. The 24 Month Period includes data up to 56 days post the last dose in the 24 month period. Poisson distribution used to construct the 95% CIs.

3. Proportion of Participants Without Radiographic Progression in Total Score Less Than or Equal to the Smallest Detectable Change (SDC) From Baseline to Months 12 and 24 Using Modified Van Der Heijde Total Sharp Score (mSvdHS) - ITT Population [Baseline to Day 729]

   Plain radiographs of hands and feet taken at baseline (BL), Day 365, and Day 729. BL and Day 365 radiographs were re-read concurrent with Day 729 films by readers blinded to sequence and treatment (a second pre-specified reading campaign). SDC defined as amount of change for which anything smaller could not be reliably distinguished from random error in measurement of simultaneously read films. Non-progression defined: change from BL (Day 1, prior to dosing) in total score less than, equal to (<=) SDC(2.2). Proportion n/m (%)=number meeting criteria (n); number analyzed (m). SDC calculated as SD/sqrt(2)*1.96/sqrt(2)with standard deviation (SD) of paired differences of change from BL in total score between 2 readers; squared root(sqrt). mSvdHS=summary of erosion severity in 32 hand and 12 foot joints. Hand joints scored 0 to 5; foot joints 0 to 10 with 0=no erosion and higher numbers indicating greater erosion severity. BL: radiographic data within 14 days or less of first dose.

4. Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 12 Months of Treatment - ITT Population [Day 1 to Day 365]

   Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post-last dose of first 12 months or start of first dose of second 12 months); denominator was overall total exposure (person-years) within this period, calculated as sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is 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.

5. Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 24 Months of Treatment - ITT Population [Day 1 to Day 729]

   Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, and all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post the last dose of the 24 Months period); denominator was overall total exposure (person-years) within this period, which was calculated as the sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express the rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is 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.

6. Proportion of Participants With Induction of Autoantibodies During the 12 Months and 24 Months Periods - ITT Population [Day 1 to Day 729]

   The induction of autoantibodies was defined as participant's antinuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) converting from a negative status at baseline to a positive status at a post-baseline measurement time point (Day 365 or Day 729). Proportion (%) = n/m, where n=number of participants with positive ANA or dsDNA at a time point and m=number of participants who had negative ANA or dsDNA at baseline. Blood samples were first tested for ANA by indirect fluorescent assay using HEp-2 Cell Line Substrate, and when positive, samples were further tested for anti-dsDNA by indirect fluorescent assay using Crithidia Luciliae Substrate.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Moderate to severe Rheumatoid arthritis (RA) according to American College of Rheumatology (ACR) criteria

• Methotrexate failure

• Naive to RA biologics

• ≤5 years duration of disease

• Disease Activity Score-28 C-reactive protein (DAS28 CRP) ≥ 3.2

• Willingness to self-inject subcutaneous (SC) drug

Exclusion Criteria:

• Previous or current medical conditions that are warnings against the use of tumor necrosis factor (TNF)-blocking agents

• History of active or chronic hepatitis

• Cancer in the last 5 years

• History of severe chronic or recurrent bacterial or viral infections

• Risk of tuberculosis

• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, Gastro-intestinal, pulmonary, cardiac, neurologic, or cerebral disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheumatology Associates, Pc	Birmingham	Alabama	United States	35205
2	University Of Alabama At Birmingham	Birmingham	Alabama	United States	35294
3	Clinical And Translational Research Center Of Alabama, Pc	Tuscaloosa	Alabama	United States	35406
4	Sun Valley Arthritis Center, Ltd.	Peoria	Arizona	United States	85381
5	Mercy Clinic Hot Springs Communities	Hot Springs	Arkansas	United States	71913
6	Talbert Medical Group	Huntington Beach	California	United States	92646
7	Allergy & Rheumatology Medical Clinic, Inc.	La Jolla	California	United States	92037
8	Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.	Long Beach	California	United States	90806
9	Irene Y. Tong	Pasadena	California	United States	91107
10	San Diego Arthritis Medical Clinic	San Diego	California	United States	92108
11	Healthcare Partners Medical Group	Torrance	California	United States	90503
12	Drs. Goldin, Nies, Klashman & Eng	Torrance	California	United States	90505
13	Inland Rheumatology & Osteoporosis Medical Group	Upland	California	United States	91786
14	Arthritis And Rheumatic Disease Specialties	Aventura	Florida	United States	33180
15	University Of Florida College Of Medicine At Jacksonville	Gainesville	Florida	United States	32610
16	Center For Arthritis And Rheumatic Diseases	Miami	Florida	United States	33173
17	Arthritis Research Of Florida, Inc.	Palm Harbor	Florida	United States	34684
18	Sarasota Arthritis Research Center	Sarasota	Florida	United States	34239
19	Miami Research Associates	South Miami	Florida	United States	33143
20	West Broward Rheumatology Associates	Tamarac	Florida	United States	33321
21	Lovelace Scientific Resources, Inc	Venice	Florida	United States	34292
22	Arthritis & Rheumatology Of Georgia	Atlanta	Georgia	United States	30342
23	Laureate Clinical Research Group	Atlanta	Georgia	United States	30342
24	Arthritis Center Of North Georgia	Gainesville	Georgia	United States	30501
25	St. Luke'S Clinic - Rheumatology	Boise	Idaho	United States	83702
26	Coeur D'Alene Arthrit Clin	Coeur D Alene	Idaho	United States	83814
27	Quincy Medical Group	Quincy	Illinois	United States	62301
28	Rockford Orthopedic Associates, Ltd.	Rockford	Illinois	United States	61107
29	Physicians Clinic Of Iowa	Cedar Rapids	Iowa	United States	52401
30	Center For Arthritis And Osteoporosis	Elizabethtown	Kentucky	United States	42701
31	Bluegrass Community Research, Inc.	Lexington	Kentucky	United States	40504
32	Klein And Associates, M.D., Pa	Cumberland	Maryland	United States	21502
33	The Center For Rheumatology And Bone Research	Wheaton	Maryland	United States	20902
34	Brigham And Women'S Hospital	Boston	Massachusetts	United States	02115
35	Mansfield Health Center	Mansfield	Massachusetts	United States	02048
36	Associated Internal Medicine Specialists	Battle Creek	Michigan	United States	49015
37	Rheumatology Pc	Kalamazoo	Michigan	United States	49009
38	Arthritis Associates Of Mississippi	Jackson	Mississippi	United States	39202
39	Physician Groups, Lc Dba	St.Louis	Missouri	United States	63131
40	Arthritis Center Of Reno	Reno	Nevada	United States	89502
41	Seacoast Arthritis And Osteoporosis Center	Dover	New Hampshire	United States	03820
42	Nashua Rheumatology	Nashua	New Hampshire	United States	03060
43	Arthritis And Osteoporosis Associates Of New Mexico	Las Cruces	New Mexico	United States	88011
44	North Shore Lij Health System	Lake Success	New York	United States	11042
45	Winthrop University Hospital	Mineola	New York	United States	11501
46	Rheumatology Associates Of Long Island	Smithtown	New York	United States	11787
47	Asheville Rheumatology & Osteoporosis Research Asso P. A.	Asheville	North Carolina	United States	28803
48	Carolina Pharmaceutical Research	Statesville	North Carolina	United States	28625
49	Health Research Of Oklahoma	Oklahoma City	Oklahoma	United States	73103
50	Health Research Institute	Oklahoma City	Oklahoma	United States	73109
51	Lynn Health Sciences Institute	Oklahoma City	Oklahoma	United States	73112
52	East Penn Rheumatology Associates, P.C.	Bethlehem	Pennsylvania	United States	18015
53	Altoona Center For Clinical Research	Duncansville	Pennsylvania	United States	16635
54	Clinical Research Center Of Reading, Llp	Wyomissing	Pennsylvania	United States	19610
55	Low Country Rheumatology, Pa	Charleston	South Carolina	United States	29406
56	Columbia Arthritis Center, P.A.	Columbia	South Carolina	United States	29204
57	Lovelace Scientific Resources, Inc.	Austin	Texas	United States	78758
58	Arthritis Centers Of Texas	Dallas	Texas	United States	75246
59	Rheumatic Disease Clinical Research Center, Llc	Houston	Texas	United States	77004
60	Center For Arthritis & Rheumatic Diseases, Pc	Chesapeake	Virginia	United States	23320
61	Rockwood Research Center	Spokane	Washington	United States	99202
62	Mountain State Clinical Research	Clarksburg	West Virginia	United States	26301
63	Rheumatic Disease Center	Glendale	Wisconsin	United States	53217
64	Local Institution	Ciudad Autonoma De Beunos Aire	Buenos Aires	Argentina	1431
65	Local Institution	Ciudad Autonoma De Buenos Aire	Buenos Aires	Argentina	1015
66	Local Institution	Ciudad Autonoma De Buenos Aire	Buenos Aires	Argentina	C1428DQG
67	Local Institution	Ciudad Autonoma	Buenos Aires	Argentina	CP1425A WC
68	Local Institution	Quilmes	Buenos Aires	Argentina	1878
69	Local Institution	Cordoba, Crd	Cordoba	Argentina	X5016KEH
70	Local Institution	Rosario	Santa Fe	Argentina	2000
71	Local Institution	San Miguel De Tucuman	Tucuman	Argentina	4000
72	Local Institution	Cordoba		Argentina	5000
73	Local Institution	San Juan		Argentina	5400
74	Local Institution	Tucuman		Argentina	4000
75	Local Institution	Winnipeg	Manitoba	Canada	R3A 1M3
76	Local Institution	Hamilton	Ontario	Canada	L8N 1Y2
77	Local Institution	Trois-Rivieres	Quebec	Canada	G8Z 1Y2
78	Local Institution	Quebec		Canada	G1V 3M7
79	Local Institution	Santiago	Providencia	Chile
80	Local Institution	Bellavista	Callao 2	Peru
81	Local Institution	Lima		Peru	LIMA 11
82	Local Institution	Lima		Peru	LIMA 27
83	Local Institution	Lima		Peru	LIMA 33
84	Local Institution	Lima		Peru

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: NCT00929864
• Other Study ID Numbers: IM101-235
• First Posted: Jun 30, 2009
• Last Update Posted: Feb 4, 2014
• Last Verified: Jan 1, 2014

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

Study Results

Participant Flow

Recruitment Details	28-October-2009 to 23-November-2012. Study conducted in biologic-naive participants with Rheumatoid Arthritis (RA) who have failed on methotrexate therapy.
Pre-assignment Detail	869 enrolled; 648 randomized; 646 randomized and treated. Reasons for not randomized: 4 pregnancy; 23 lost to follow-up; 133 administrative reasons by Sponsor; 4 no longer met study criteria; 7 other; 50 had reasons missing. Two participants randomized/not treated: no longer met study criteria. Randomization stratified by DAS28-CRP>5.1, <=5.1

Arm/Group Title	125 mg Abatacept SC Weekly	40 mg Adalimumab SC Biweekly
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, biweekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Period Title: Overall Study
STARTED	318	328
COMPLETED	252	245
NOT COMPLETED	66	83

Baseline Characteristics

Arm/Group Title	Abatacept	Adalimumab	Total
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Total of all reporting groups
Overall Participants	318	328	646
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (12.6)	51.0 (12.8)	51.2 (12.7)
Sex: Female, Male (Count of Participants)
Female	259 81.4%	270 82.3%	529 81.9%
Male	59 18.6%	58 17.7%	117 18.1%
Region of Enrollment (participants) [Number]
North America	230 72.3%	235 71.6%	465 72%
South America	88 27.7%	93 28.4%	181 28%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Participants Meeting the American College of Rheumatology (ACR) Criteria of 20% Improvement (ACR20) After 12 Months of Treatment - Intent to Treat Population
Description	Proportion(%)=number of participants meeting criteria (n) divided by number of participants who received drug (N). The ACR score indicates degree of improvement in a patient's rheumatoid arthritis (RA), based on guidelines set forth by the ACR and represents a percentage. To qualify a ACR20 score, patient must have >=20% fewer tender joints and >=20% fewer swollen joints and show 20% improvement from baseline in at least 3 of: patient overall assessment of his/her RA, physician global assessment of the patient's RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein (CRP) test (to assess inflammation). Baseline was Day 1. Randomization was stratified using screening Disease Activity Score-28 (DAS28) CRP, a composite of 4 variables: number of tender joints/28, number of swollen joints/28, CRP in mg/L and participant assessment of disease activity with visual analogue scale.
Time Frame	Day 1 to Day 365

Outcome Measure Data

Analysis Population Description

The intent to treat (ITT) analysis population was defined as all participants randomized into the study who received at least one dose of study drug. n/N = 206/318 and 208/328 in the abatacept and adalimumab arms, respectively.

Arm/Group Title	Abatacept	Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Measure Participants	318	328
Number (95% Confidence Interval) [percentage of participants]	64.8 20.4%	63.4 19.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	The null and alternative hypotheses are H0: T - C<= δ vs. Ha:T - C > δ, where T is the treatment effect of abatacept, C is the effect of active control (adalimumab),and δ is non-inferiority margin. Abatacept is defined as δ non-inferior to adalimumab when H0 is rejected. More specifically, if the lower bound of the 95% two-sided confidence interval for C-T is greater than δ,, then that Abatacept is δ non-inferior to adalimumab can be claimed.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis tested for non-inferiority. Abatacept will be considered non-inferior to adalimumab if the upper limit of the 95% two-sided CI of difference in ACR20 response rates between the adalimumab arm and the abatacept arm is smaller than or equal to 12%. Estimate and 95% confidence interval (CI) for difference based on minimum risk weights method with randomization stratification of screening Disease Activity Score-28 (DAS28) c-reactive protein (CRP).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab at Day 365
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -5.6 to 9.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population
Description	n=number of participants with a pre-specified local injection site reaction event, N=number of participants at risk. Proportion (%) = n/N. 12 Months includes data up to 56 days post last dose of the first 12 months Period or start of the first dose of second 12 months period.
Time Frame	Day 1 to 12 Months

Outcome Measure Data

Analysis Population Description

The ITT analysis population was defined as all participants randomized into the study who received at least one dose of study drug. n/N = 12/318, 30/328 in abatacept and adalimumab, respectively. CI based on normal approximation.

Arm/Group Title	Abatacept	Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Measure Participants	318	328
Number (95% Confidence Interval) [percentage of participants]	3.8 1.2%	9.1 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis is p-value of difference in proportions. n=number of participants with event, N=number of participants at risk. Proportion = n/N. In order to maintain the overall type I error rate of 0.05 for testing both the primary non-inferiority hypothesis and the key secondary local injection site reaction (LISR) hypothesis, the LISR hypothesis was tested at the 5% significance level only after the primary non-inferiority hypothesis is established at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-5.37
	Confidence Interval	(2-Sided) 95%; -9.13 to -1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Incidence Rate of Local Injection Site Reactions (Pre-specified) Reported During 24 Month Period - ITT Population
Description	Incidence Rate: (incidence/100 person-years) = number of participants with event * 100 /exposure (person-years) Exposure (person-years) = the sum over all participants of the exposure per participant in the 24 months (censored at the time of first occurrence of AE) expressed in days, divided by 365.25. The 24 Month Period includes data up to 56 days post the last dose in the 24 month period. Poisson distribution used to construct the 95% CIs.
Time Frame	Day 1 to Day 729

Outcome Measure Data

Analysis Population Description

ITT population: all participants randomized into the study who received at least one dose of study drug. Participants with a pre-specified local injection site event at 24 Months: 13, 34, in abatacept and adalimumab arms, respectively. 24 Month Exposure=579.21, 532.99, respectively.

Arm/Group Title	Abatacept	Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Measure Participants	318	328
Number (95% Confidence Interval) [incidence/100 person years]	2.24	6.38

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis of incidence rate at 24 months. Point estimate and 95% CI. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-4.13
	Confidence Interval	(2-Sided) 95%; -6.55 to -1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Proportion of Participants Without Radiographic Progression in Total Score Less Than or Equal to the Smallest Detectable Change (SDC) From Baseline to Months 12 and 24 Using Modified Van Der Heijde Total Sharp Score (mSvdHS) - ITT Population
Description	Plain radiographs of hands and feet taken at baseline (BL), Day 365, and Day 729. BL and Day 365 radiographs were re-read concurrent with Day 729 films by readers blinded to sequence and treatment (a second pre-specified reading campaign). SDC defined as amount of change for which anything smaller could not be reliably distinguished from random error in measurement of simultaneously read films. Non-progression defined: change from BL (Day 1, prior to dosing) in total score less than, equal to (<=) SDC(2.2). Proportion n/m (%)=number meeting criteria (n); number analyzed (m). SDC calculated as SD/sqrt(2)*1.96/sqrt(2)with standard deviation (SD) of paired differences of change from BL in total score between 2 readers; squared root(sqrt). mSvdHS=summary of erosion severity in 32 hand and 12 foot joints. Hand joints scored 0 to 5; foot joints 0 to 10 with 0=no erosion and higher numbers indicating greater erosion severity. BL: radiographic data within 14 days or less of first dose.
Time Frame	Baseline to Day 729

Outcome Measure Data

Analysis Population Description

ITT population: all subjects randomized into the study who received at least one dose of study drug. Number analyzed: m=number of ITT participants with both BL and post-BL total score: Day 365: m=295, 297;Day 729 m=257 and 260, in abatacept and adalimumab arms, respectively. n=number without progression. CI based on normal approximation.

Arm/Group Title	Abatacept	Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Measure Participants	295	297
Day 365 n=259, 263; m=295, 297	87.8 27.6%	88.6 27%
Day 729 n=218, 218; m=257, 260	84.8 26.7%	83.8 25.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	This analysis is for Day 365.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab at Day 365
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -6.5 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	This analysis is for Day 729.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab at Day 729
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -5.5 to 7.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 12 Months of Treatment - ITT Population
Description	Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post-last dose of first 12 months or start of first dose of second 12 months); denominator was overall total exposure (person-years) within this period, calculated as sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is 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.
Time Frame	Day 1 to Day 365

Outcome Measure Data

Analysis Population Description

The intent to treat (ITT) analysis population was defined as all subjects randomized into the study who received at least one dose of study drug. Poisson distribution was used to construct the 95% CIs.

Arm/Group Title	Abatacept	Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Measure Participants	318	328
SAE (number with event=32, 30)	11.06	10.26
Serious Infections (number with event=7, 9)	2.32	2.99
Opportunistic infections (number with event=1, 1)	0.33	0.33
Discontinuation (number with event=44, 59)	14.79	20.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of SAE at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; -4.51 to 6.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of Serious Infections and Infestations at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -3.27 to 1.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of Opportunistic Infections at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.92 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of discontinuation for any cause at 12 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-5.32
	Confidence Interval	(2-Sided) 95%; -12.06 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 24 Months of Treatment - ITT Population
Description	Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, and all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post the last dose of the 24 Months period); denominator was overall total exposure (person-years) within this period, which was calculated as the sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express the rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is 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.
Time Frame	Day 1 to Day 729

Outcome Measure Data

Analysis Population Description

The intent to treat (ITT) analysis population was defined as all subjects randomized into the study who received at least one dose of study drug. Poisson distribution was used to construct the 95% CIs.

Arm/Group Title	Abatacept	Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Measure Participants	318	328
SAE Incidence Rate (number with event=44, 54)	13.8	16.5
Serious Infections (number with event=12, 19)	3.8	5.8
Opportunistic infections (number with event=2, 5)	0.6	1.5
Discontinuation (number with event=66, 83)	20.8	25.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of SAE at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-1.91
	Confidence Interval	(2-Sided) 95%; -5.43 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of Serious infections and infestations Adverse Events at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-1.24
	Confidence Interval	(2-Sided) 95%; -3.12 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of opportunistic infections at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -1.39 to 0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for incidence rate of discontinuations (all cause) at 24 months. Point estimate and 95% CI for treatment difference. Poisson distribution was used to construct the 95% CIs.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-3.10
	Confidence Interval	(2-Sided) 95%; -7.13 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Proportion of Participants With Induction of Autoantibodies During the 12 Months and 24 Months Periods - ITT Population
Description	The induction of autoantibodies was defined as participant's antinuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) converting from a negative status at baseline to a positive status at a post-baseline measurement time point (Day 365 or Day 729). Proportion (%) = n/m, where n=number of participants with positive ANA or dsDNA at a time point and m=number of participants who had negative ANA or dsDNA at baseline. Blood samples were first tested for ANA by indirect fluorescent assay using HEp-2 Cell Line Substrate, and when positive, samples were further tested for anti-dsDNA by indirect fluorescent assay using Crithidia Luciliae Substrate.
Time Frame	Day 1 to Day 729

Outcome Measure Data

Analysis Population Description

ITT population was defined as all participants randomized into the study who received at least one dose of study drug; number analyzed was ITT participants with data at each time point and who had negative ANA or dsDNA at baseline (m)

Arm/Group Title	Abatacept	Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.	Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
Measure Participants	318	328
Day 365 ANA; n=12, 28; m=229, 210	5.2 1.6%	13.3 4.1%
Day 365 anti-dsDNA; n=1, 29; m=299, 293	0.3 0.1%	9.9 3%
Day 729 ANA; n=12, 24; m=190, 163	6.3 2%	14.7 4.5%
Day 729 anti-dsDNA; n=0, 29; m=248, 237	0.0 0%	12.2 3.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for ANA at Day 365. Point estimate and 95% CI for treatment difference.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-8.1
	Confidence Interval	(2-Sided) 95%; -13.9 to -2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for ANA at Day 729. Point estimate and 95% CI for treatment difference
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-8.4
	Confidence Interval	(2-Sided) 95%; -15.3 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for dsDNA at Day 365. Point estimate and 95% CI for treatment difference.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-9.6
	Confidence Interval	(2-Sided) 95%; -13.4 to -5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abatacept, Adalimumab
	Comments	Analysis for dsDNA at Day 729. Point estimate and 95% CI for treatment difference.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference from adalimumab
	Estimated Value	-12.2
	Confidence Interval	(2-Sided) 95%; -16.9 to -7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Includes data up to 56 days post the last dose in the 24 months period.
Adverse Event Reporting Description	Note: One participant in the abatacept arm had an SAE with no preferred term identified. Therefore, there were 44 participants with SAEs reported in the Outcome measure on the Rate of SAEs but since a preferred term was not identified, a total of 43 are identified in the SAEs below.
Arm/Group Title	Abatacept		Adalimumab
Arm/Group Description	Abatacept 125 mg weekly subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.		Adalimumab 40 mg, bi-weekly (every 14 days) subcutaneous (SC) self administered injections for 24 months (729 days). Methotrexate (MTX) was co-administered; a stable dose of maximum tolerated methotrexate (minimum of 15 mg and maximum of 25 mg) per week. Participants were allowed to enroll with MTX doses <15 mg/week but >= 7.5 mg/week if intolerance to higher doses was documented. Participants could also enroll while receiving hydrochloroquine or sulfasalazine in addition to MTX.
All Cause Mortality
	Abatacept		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Abatacept		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/318 (13.5%)		54/328 (16.5%)
Blood and lymphatic system disorders
Pancytopenia	1/318 (0.3%)		0/328 (0%)
Anaemia	0/318 (0%)		1/328 (0.3%)
Cardiac disorders
Cardiac arrest	1/318 (0.3%)		0/328 (0%)
Cardiomyopathy	0/318 (0%)		1/328 (0.3%)
Palpitations	0/318 (0%)		1/328 (0.3%)
Myocardial infarction	1/318 (0.3%)		0/328 (0%)
Acute coronary syndrome	0/318 (0%)		1/328 (0.3%)
Coronary artery disease	1/318 (0.3%)		0/328 (0%)
Angina unstable	1/318 (0.3%)		0/328 (0%)
Tachycardia	1/318 (0.3%)		0/328 (0%)
Angina pectoris	2/318 (0.6%)		1/328 (0.3%)
Cardiac failure congestive	1/318 (0.3%)		1/328 (0.3%)
Ear and labyrinth disorders
Vertigo	0/318 (0%)		1/328 (0.3%)
Endocrine disorders
Goitre	0/318 (0%)		1/328 (0.3%)
Gastrointestinal disorders
Abdominal hernia	1/318 (0.3%)		0/328 (0%)
Gastritis	1/318 (0.3%)		1/328 (0.3%)
Lower gastrointestinal haemorrhage	1/318 (0.3%)		0/328 (0%)
Diaphragmatic hernia	0/318 (0%)		1/328 (0.3%)
Abdominal pain	1/318 (0.3%)		1/328 (0.3%)
Hiatus hernia	1/318 (0.3%)		0/328 (0%)
Small intestinal obstruction	1/318 (0.3%)		0/328 (0%)
Pancreatitis	1/318 (0.3%)		1/328 (0.3%)
Pancreatitis acute	0/318 (0%)		1/328 (0.3%)
General disorders
Hernia obstructive	0/318 (0%)		1/328 (0.3%)
Non-cardiac chest pain	1/318 (0.3%)		3/328 (0.9%)
Drug withdrawal syndrome	1/318 (0.3%)		0/328 (0%)
Chest pain	2/318 (0.6%)		0/328 (0%)
Hepatobiliary disorders
Cholelithiasis	2/318 (0.6%)		1/328 (0.3%)
Cholecystitis acute	3/318 (0.9%)		0/328 (0%)
Biliary colic	1/318 (0.3%)		0/328 (0%)
Cholecystitis	1/318 (0.3%)		1/328 (0.3%)
Cholecystitis chronic	0/318 (0%)		1/328 (0.3%)
Infections and infestations
Helicobacter gastritis	1/318 (0.3%)		0/328 (0%)
Diverticulitis	0/318 (0%)		2/328 (0.6%)
Gastroenteritis	1/318 (0.3%)		1/328 (0.3%)
Groin abscess	0/318 (0%)		1/328 (0.3%)
Cellulitis	0/318 (0%)		1/328 (0.3%)
Oral candidiasis	1/318 (0.3%)		0/328 (0%)
Clostridial infection	0/318 (0%)		1/328 (0.3%)
Pneumonia	3/318 (0.9%)		4/328 (1.2%)
Pulmonary tuberculosis	0/318 (0%)		1/328 (0.3%)
Arthritis bacterial	0/318 (0%)		3/328 (0.9%)
Bursitis infective staphylococcal	0/318 (0%)		1/328 (0.3%)
Peritonsillar abscess	1/318 (0.3%)		0/328 (0%)
Abscess limb	1/318 (0.3%)		0/328 (0%)
Disseminated tuberculosis	0/318 (0%)		1/328 (0.3%)
Histoplasmosis disseminated	0/318 (0%)		1/328 (0.3%)
Bronchitis	0/318 (0%)		1/328 (0.3%)
Chest wall abscess	0/318 (0%)		1/328 (0.3%)
Meningitis	0/318 (0%)		1/328 (0.3%)
Pneumonia mycoplasmal	1/318 (0.3%)		0/328 (0%)
Soft tissue infection	1/318 (0.3%)		0/328 (0%)
Urinary tract infection	3/318 (0.9%)		0/328 (0%)
Injury, poisoning and procedural complications
Animal bite	0/318 (0%)		1/328 (0.3%)
Humerus fracture	0/318 (0%)		1/328 (0.3%)
Hip fracture	0/318 (0%)		1/328 (0.3%)
Investigations
Human papilloma virus test positive	1/318 (0.3%)		0/328 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/318 (0%)		1/328 (0.3%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/318 (0%)		1/328 (0.3%)
Muscular weakness	1/318 (0.3%)		0/328 (0%)
Cervical spinal stenosis	1/318 (0.3%)		1/328 (0.3%)
Arthritis	0/318 (0%)		2/328 (0.6%)
Joint effusion	1/318 (0.3%)		0/328 (0%)
Osteoarthritis	1/318 (0.3%)		1/328 (0.3%)
Osteoporotic fracture	0/318 (0%)		1/328 (0.3%)
Arthralgia	1/318 (0.3%)		0/328 (0%)
Neck pain	0/318 (0%)		1/328 (0.3%)
Rotator cuff syndrome	2/318 (0.6%)		0/328 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia	1/318 (0.3%)		0/328 (0%)
Prostate cancer	1/318 (0.3%)		0/328 (0%)
Malignant melanoma	0/318 (0%)		1/328 (0.3%)
Small cell lung cancer stage unspecified	0/318 (0%)		1/328 (0.3%)
Squamous cell carcinoma of skin	2/318 (0.6%)		0/328 (0%)
Transitional cell carcinoma	0/318 (0%)		2/328 (0.6%)
Squamous cell carcinoma	1/318 (0.3%)		0/328 (0%)
Benign pancreatic neoplasm	0/318 (0%)		1/328 (0.3%)
Breast cancer	0/318 (0%)		1/328 (0.3%)
Lung neoplasm malignant	1/318 (0.3%)		0/328 (0%)
Uterine cancer	1/318 (0.3%)		0/328 (0%)
Basal cell carcinoma	0/318 (0%)		2/328 (0.6%)
Diffuse large B-cell lymphoma	1/318 (0.3%)		0/328 (0%)
Nervous system disorders
Convulsion	1/318 (0.3%)		0/328 (0%)
Lacunar infarction	1/318 (0.3%)		0/328 (0%)
Syncope	1/318 (0.3%)		1/328 (0.3%)
Transient ischaemic attack	0/318 (0%)		1/328 (0.3%)
Lethargy	1/318 (0.3%)		0/328 (0%)
Presyncope	1/318 (0.3%)		0/328 (0%)
Carotid artery stenosis	0/318 (0%)		2/328 (0.6%)
Cerebrovascular accident	0/318 (0%)		1/328 (0.3%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/318 (0%)		1/328 (0.3%)
Psychiatric disorders
Drug dependence	1/318 (0.3%)		0/328 (0%)
Renal and urinary disorders
Calculus urinary	1/318 (0.3%)		0/328 (0%)
Renal failure acute	0/318 (0%)		1/328 (0.3%)
Reproductive system and breast disorders
Endometrial hyperplasia	1/318 (0.3%)		0/328 (0%)
Cervical dysplasia	1/318 (0.3%)		0/328 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/318 (0%)		1/328 (0.3%)
Asthma	0/318 (0%)		1/328 (0.3%)
Bronchospasm	1/318 (0.3%)		0/328 (0%)
Pleural effusion	0/318 (0%)		1/328 (0.3%)
Chronic obstructive pulmonary disease	0/318 (0%)		1/328 (0.3%)
Hypoxia	0/318 (0%)		1/328 (0.3%)
Pulmonary embolism	1/318 (0.3%)		0/328 (0%)
Pulmonary artery thrombosis	0/318 (0%)		1/328 (0.3%)
Epistaxis	1/318 (0.3%)		0/328 (0%)
Respiratory failure	0/318 (0%)		1/328 (0.3%)
Vascular disorders
Aortic aneurysm	1/318 (0.3%)		0/328 (0%)
Peripheral artery aneurysm	1/318 (0.3%)		0/328 (0%)
Deep vein thrombosis	0/318 (0%)		1/328 (0.3%)
Other (Not Including Serious) Adverse Events
	Abatacept		Adalimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	237/318 (74.5%)		232/328 (70.7%)
Gastrointestinal disorders
Diarrhoea	29/318 (9.1%)		23/328 (7%)
Vomiting	11/318 (3.5%)		18/328 (5.5%)
Nausea	26/318 (8.2%)		28/328 (8.5%)
General disorders
Fatigue	21/318 (6.6%)		20/328 (6.1%)
Oedema peripheral	22/318 (6.9%)		17/328 (5.2%)
Infections and infestations
Gastroenteritis	16/318 (5%)		13/328 (4%)
Nasopharyngitis	61/318 (19.2%)		57/328 (17.4%)
Sinusitis	51/318 (16%)		37/328 (11.3%)
Upper respiratory tract infection	64/318 (20.1%)		55/328 (16.8%)
Influenza	21/318 (6.6%)		18/328 (5.5%)
Bronchitis	49/318 (15.4%)		43/328 (13.1%)
Pharyngitis	17/318 (5.3%)		20/328 (6.1%)
Urinary tract infection	41/318 (12.9%)		32/328 (9.8%)
Musculoskeletal and connective tissue disorders
Back pain	39/318 (12.3%)		39/328 (11.9%)
Arthralgia	9/318 (2.8%)		17/328 (5.2%)
Nervous system disorders
Headache	32/318 (10.1%)		38/328 (11.6%)
Psychiatric disorders
Depression	17/318 (5.3%)		14/328 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	22/318 (6.9%)		27/328 (8.2%)
Skin and subcutaneous tissue disorders
Rash	13/318 (4.1%)		27/328 (8.2%)
Vascular disorders
Hypertension	21/318 (6.6%)		25/328 (7.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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