BMS-188667 in Children and Adolescents With Juvenile Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT00095173
• Recruitment Status: Completed
• First Posted: November 2, 2004
• Results First Posted: January 18, 2017
• Last Update Posted: January 18, 2017
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Juvenile Rheumatoid Arthritis
• Interventions: Drug: Abatacept; Drug: Placebo
• Enrollment: 214

Participant Flow

Recruitment Details
Pre-assignment Details	214 enrolled; in Per A, 190 treated; 24 not treated due to screening failures.170 completed Per A, 123 responders qualified to enter Per B. One subject did not enter Per B; 122 responders were randomized, 60 abatacept and 62 placebo. 36 of 47 Per A non-responders re-entered at Per C. Protocol violation occurred; 5yr old participant.

Arm/Group Title	Abatacept (All Participants in Period A)	Abatacept (Period B)	Placebo (Period B)	Abatacept (Period A Non-Responders in Period C)	Abatacept (Period C)	Placebo (Period B) to Abatacept (Period C)
Arm/Group Description	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses.	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare (Period B).	Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion.	Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) or once a month for up to 5 years (Period C).	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.	Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
Period Title: Open-Label Lead-In Phase (Period A)
Started	190	0	0	0	0	0
Completed	170	0	0	0	0	0
Not Completed	20	0	0	0	0	0
Reason Not Completed
Adverse Event	1	0	0	0	0	0
Lack of Efficacy	17	0	0	0	0	0
Withdrawal by Subject	1	0	0	0	0	0
Other	1	0	0	0	0	0
Period Title: Double-Blind Phase (Period B)
Started	0 [1]	60 [2]	62 [2]	0	0	0
Completed	0	49	31	0	0	0
Not Completed	0	11	31	0	0	0
Reason Not Completed
Lack of Efficacy	0	10	31	0	0	0
Withdrawal by Subject	0	1	0	0	0	0
[1] All participants did not continue; responders entered Period B; non-responders re-entered Period C.; [2] 123 responders from Period A qualified;122 entered and were randomized to abatacept and placebo.
Period Title: Open-Label Extension Phase (Period C)
Started	0	0	0	36 [1]	58 [2]	59 [3]
Completed	0	0	0	13	29	27
Not Completed	0	0	0	23	29	32
Reason Not Completed
Death	0	0	0	0	0	1
Adverse Event	0	0	0	1	2	3
Lack of Efficacy	0	0	0	11	5	8
Lost to Follow-up	0	0	0	2	5	6
Withdrawal by Subject	0	0	0	4	6	0
No Longer Meets Study Criteria	0	0	0	0	1	1
Poor/Non-Compliance	0	0	0	0	2	2
Pregnancy	0	0	0	1	2	3
Other	0	0	0	4	6	8
[1] Participants were non-responders from Period A who re-entered in Period C.; [2] Includes 47 who completed Period B with no flare and 11 who discontinued Period B due to a flare; [3] Includes 33 who discontinued Period B due to a flare and 26 who completed Period B with no flare

Baseline Characteristics

Arm/Group Title		Abatacept (All Participants in Period A)
Arm/Group Description		Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes,once every 2 weeks for 3 doses, then monthly up to 6 months unless a disease flare discontinued the patient earlier.
Overall Number of Baseline Participants		190
Baseline Analysis Population Description		All treated participants in the Lead-In Phase (Period A)
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	190 participants
		13.0; (5.0 to 17.0)
Gender; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	190 participants
	Female	137 72.1%
	Male	53 27.9%

Outcome Measures

1. Primary Outcome

Title	Time to Occurrence of Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease Flare During Double-Blind Phase (Period B)
Description	Time to flare is defined as the elapsed number of days between the first dose date in Period B and the study day that disease flare is confirmed. All of the following criteria must be met to be defined as a flare: > 30% worsening in at least 3 of the 6 JRA/JIA core response variables; > 30% improvement in not more than 1 of the 6 JRA/JIA core set variables; ≥ 2 cm of worsening must be present if the Physician or Parent Global Assessment is used to define flare; worsening in ≥ 2 joints must be present if the number of active joints or joints with limitation of motion is used to define flare based on changes in the surrogate marker, erythrocyte sedimentation rate (ESR)
Time Frame	Period B (Day 113 to Day 282)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Abatacept (Period B)	Placebo (Period B)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare.	Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion.
Overall Number of Participants Analyzed	60	62
Median (Full Range); Unit of Measure: months
	NA [1]; (NA to NA)	6; (0.73 to 6.87)

[1]

Fewer than 50% of the participants in the abatacept group experienced a flare, therefore the median time to flare is known to exceed 6 months, but cannot be estimated.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept (Period B), Placebo (Period B)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.31
	Confidence Interval	(2-Sided) 95%; 0.16 to 0.59
	Estimation Comments	Abatacept over placebo

2. Secondary Outcome

Title	Number of Participants With a Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease With a Flare During Double-Blind Phase (Period B)
Description	All of the following criteria must be met to be defined as a flare: > 30% worsening in at least 3 of the 6 JRA/JIA core response variables; > 30% improvement in not more than 1 of the 6 JRA/JIA core set variables; ≥ 2 cm of worsening must be present if the Physician or Parent Global Assessment is used to define flare; worsening in ≥ 2 joints must be present if the number of active joints or joints with limitation of motion is used to define flare based on changes in the surrogate marker, erythrocyte sedimentation rate (ESR)
Time Frame	Period B (Day 113 to Day 282)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Abatacept (Period B)	Placebo (Period B)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare.	Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion.
Overall Number of Participants Analyzed	60	62
Measure Type: Number; Unit of Measure: participants
	12	33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept (Period B), Placebo (Period B)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Lead-In Phase (Period A)
Description	AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1).
Time Frame	Period A (Day 1 to Day 113)

Outcome Measure Data

Analysis Population Description

All treated participants in Periods A

Arm/Group Title	Abatacept (All Participants in Period A)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses.
Overall Number of Participants Analyzed	190
Measure Type: Number; Unit of Measure: participants
SAE	6
Treatment-Related AE	0
All Deaths	0
Treatment-Related Deaths	0
Discontinuation of Study Drug due to AEs	1

4. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Double-Blind Phase (Period B)
Description	AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1).
Time Frame	Period B (Day 113 to Day 282)

Outcome Measure Data

Analysis Population Description

All treated participants in Periods B

Arm/Group Title	Abatacept (Period B)	Placebo (Period B)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare.	Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion.
Overall Number of Participants Analyzed	60	62
Measure Type: Number; Unit of Measure: participants
SAE	0	2
Treatment-Related AE	0	0
All Deaths	0	0
Treatment-Related Deaths	0	0
Discontinuation of Study Drug due to AEs	0	0

5. Secondary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Phase (Period C)
Description	AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 85 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1).
Time Frame	Period C (Day 282 to end of study)

Outcome Measure Data

Analysis Population Description

All treated participants in Period C

Arm/Group Title	Abatacept (Period A Non-Responders in Period C)	Abatacept (Period C)	Placebo (Period B) to Abatacept (Period C)
Arm/Group Description:	Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C).	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.	Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
Overall Number of Participants Analyzed	36	58	59
Measure Type: Number; Unit of Measure: participants
SAE	9	9	12
Treatment-Related AE	2	4	3
All Deaths	0	0	1
Treatment-Related Deaths	0	0	0
Discontinuation of Study Drug due to AEs	1	2	3

6. Secondary Outcome

Title	Median Percent Change From Baseline in JRA/JIA Core Set Variables During Double-Blind Phase (Period B)
Description	Percent change from baseline was calculated from the difference between post-baseline and baseline divided by baseline multiplied by 100 and reported as the range between 25th and 75th percentile, not full range; American College of Rheumatology (ACR) Pediatric 30 JRA/JIA core set variables include active joints, limited range of motion, physician global assessment of disease severity, parent global assessment of overall well-being, change in physical function as measured by the Childhood Health Assessment Questionnaire (CHAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity was assessed by the physician and parent on a 0-100 mm visual analog scale (VAS). Low values represent low severity of disease and good well-being whereas high values represent highly severe disease and very poor well-being.
Time Frame	Period B (Day 113 to Day 282)

Outcome Measure Data

Analysis Population Description

All treated participants in Period B

Arm/Group Title	Abatacept (Period B)	Placebo (Period B)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare.	Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion.
Overall Number of Participants Analyzed	60	62
Median (Inter-Quartile Range); Unit of Measure: percentage change from baseline
Active Joints	-20.9; (-92.0 to 17.86)	50.00; (0.00 to 100.0)
Joints with LOM	0.00; (-45.5 to 0.00)	50.00; (0.00 to 100.0)
Physician Global Assessment	-29.8; (-86.3 to 22.48)	55.95; (-31.3 to 250.0)
Parent Global Assessment	-11.2; (-56.8 to 28.41)	8.39; (-31.8 to 100.0)
CHAQ Disability Index	0.00; (-38.9 to 2.17)	0.00; (-13.3 to 55.56)
ESR	0.00; (-20.7 to 50.00)	20.50; (-14.3 to 92.00)
CRP	0.00; (-46.6 to 67.00)	6.25; (-33.3 to 150.0)

7. Secondary Outcome

Title	Median Percent Change From Baseline in JRA/JIA Core Set Variables During Open-Label Phase (Period C)
Description	Percent change from baseline was calculated from the difference between post-baseline and baseline divided by baseline multiplied by 100 and reported as the range between 25th and 75th percentile, not full range; American College of Rheumatology (ACR) Pediatric 30 JRA/JIA core set variables include active joints, limited range of motion, physician's global assessment of disease severity, parent global assessment of overall well-being, change in physical function as measured by the Childhood Health Assessment Questionnaire (CHAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity was assessed by the physician and parent on a 0-100 mm visual analog scale (VAS). Low values represent low severity of disease and good well-being whereas high values represent highly severe disease and very poor well-being.
Time Frame	Period C (Day 282 to end of study)

Outcome Measure Data

Analysis Population Description

All treated participants in Period C

Arm/Group Title	Abatacept (Period A Non-Responders in Period C)	Abatacept (Period C)	Placebo (Period B) to Abatacept (Period C)
Arm/Group Description:	Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C).	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.	Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
Overall Number of Participants Analyzed	36	58	59
Median (Inter-Quartile Range); Unit of Measure: percentage change from baseline
Active Joints	-26.7; (-66.7 to 0.00)	-70.2; (-94.1 to -50.0)	-82.4; (-100 to -62.5)
Joints with Limited Range of Motion	0.00; (-33.3 to 36.67)	-50.0; (-75.0 to -27.3)	-71.4; (-86.2 to -23.1)
Physician Global Assessment of Disease Severity	-31.9; (-50.0 to -9.33)	-75.0; (-91.3 to -52.3)	-81.8; (-91.4 to -64.3)
Parent Global Assessment of Overall Well-Being	1.96; (-19.6 to 26.67)	-62.7; (-93.8 to -27.5)	-63.9; (-84.2 to -38.8)
CHAQ Disability Index	14.14; (-16.7 to 100.0)	-56.7; (-81.8 to -18.2)	-45.5; (-75.0 to -12.5)
ESR	20.87; (-15.5 to 83.77)	-27.3; (-54.8 to 20.00)	-24.2; (-50.0 to 0.00)
CRP	0.00; (-31.6 to 43.68)	-33.8; (-84.4 to 54.84)	-27.8; (-75.0 to 11.11)

8. Secondary Outcome

Title	Events of Special Interest During Open-Label Lead-In Phase (Period A), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies
Description	The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest.
Time Frame	Period A (Day 1 to Day 113)

Outcome Measure Data

Analysis Population Description

All treated participants in Period A

Arm/Group Title	Abatacept (All Participants in Period A)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses.
Overall Number of Participants Analyzed	190
Measure Type: Number; Unit of Measure: participants
Infections and Infestations	68
Peri-Infusional AEs	30
Autoimmune Disorders	2
Malignancies	0

9. Secondary Outcome

Title	Events of Special Interest During Double-Blind Phase (Period B), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies
Description	The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest.
Time Frame	Period B (Day 113 to Day 282)

Outcome Measure Data

Analysis Population Description

All treated participants in Period B

Arm/Group Title	Abatacept (Period B)	Placebo (Period B)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare.	Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion.
Overall Number of Participants Analyzed	60	62
Measure Type: Number; Unit of Measure: participants
Infections and Infestations	27	27
Peri-Infusional AEs	2	2
Autoimmune Disorders	0	0
Malignancies	0	0

10. Secondary Outcome

Title	Events of Special Interest During Open-Label Phase (Period C), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies
Description	The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest.
Time Frame	Period C (Day 282 up to 56 days after the last dose of study medication)

Outcome Measure Data

Analysis Population Description

All treated participants in Period C

Arm/Group Title	Abatacept (All Participants in Period C)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
Overall Number of Participants Analyzed	153
Measure Type: Number; Unit of Measure: participants
Infections and Infestations	120
Peri-Infusional AEs	22
Autoimmune Disorders	7
Malignancies	1

11. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology (ACR) Pediatric 30 (ACRP30), ACR Pediatric 50, ACR Pediatric 70, ACR Pediatric 90, and Inactive Disease Status Erythrocyte Sedimentation Rate (ESR) Response Rate
Description	The ACRP30 response criteria were defined as a ≥ 30% improvement over baseline in ESR. ACRP 50, 70, and 90 responses were defined similarly with 50%, 70%, and 90% improvements required, respectively.
Time Frame	Day 113, Day 282, and Day 2047

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Abatacept (Period A Non-Responders in Period C)	Abatacept (Period C)	Placebo (Period B) to Abatacept (Period C)
Arm/Group Description:	Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C).	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.	Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
Overall Number of Participants Analyzed	36	58	59
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
ACR Pediatric 30 (ESR) at Day 113	0 [1]; (NA to NA)	100 [2]; (NA to NA)	100 [2]; (NA to NA)
ACR Pediatric 30 (ESR) at Day 282	NA [3]; (NA to NA)	84.5; (75.2 to 93.8)	67.8; (55.9 to 79.7)
ACR Pediatric 30 (ESR) at Day 2047	69.2; (44.1 to 94.3)	97.0; (91.1 to 100)	86.7; (74.5 to 98.8)
ACR Pediatric 50 (ESR) at Day 113	0 [1]; (NA to NA)	65.5; (53.3 to 77.7)	88.1; (79.9 to 96.4)
ACR Pediatric 50 (ESR) at Day 282	NA [3]; (NA to NA)	79.3; (68.9 to 89.7)	52.5; (39.8 to 65.3)
ACR Pediatric 50 (ESR) at Day 2047	69.2; (44.1 to 94.3)	93.9; (85.8 to 100.0)	80.0; (65.7 to 94.3)
ACR Pediatric 70 (ESR) at Day 113	0 [1]; (NA to NA)	37.9; (25.4 to 50.4)	49.2; (36.4 to 61.9)
ACR Pediatric 70 (ESR) at Day 282	NA [3]; (NA to NA)	55.2; (42.4 to 68.0)	30.5; (18.8 to 42.3)
ACR Pediatric 70 (ESR) at Day 2047	53.8; (26.7 to 80.9)	78.8; (64.8 to 92.7)	63.3; (46.1 to 80.6)
ACR Pediatric 90 (ESR) at Day 113	0 [1]; (NA to NA)	17.2; (7.5 to 27.0)	22.0; (11.5 to 32.6)
ACR Pediatric 90 (ESR) at Day 282	NA [3]; (NA to NA)	41.4; (28.7 to 54.1)	15.3; (6.1 to 24.4)
ACR Pediatric 90 (ESR) at Day 2047	38.5; (12.0 to 64.9)	66.7; (50.6 to 82.8)	40.0; (22.5 to 57.5)

[1]

No participants with response

[2]

Confidence interval not applicable if result is 100%

[3]

No participants in this group

12. Secondary Outcome

Title	Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Lead-In Phase (Period A)
Description	Marked abnormalities were pre-defined as changes in lab tests that occurred after drug infusion and were reported relative to the normal range for each analyte. Hemoglobin, 11.6-14.8 grams per deciliter (g/dL);Hematocrit, 36.0-50.0 percent;Erythrocytes, 3.80-5.10x10*6 cells per microliter (c/uL);Platelets, 140-44 cells per liter (c/L);Leukocytes, 4.00-12.50 c/uL;Absolute Neutrophils + Bands, if <1.00x10^3 c/uL;Absolute Lymphocytes, if <0.72x10^3 or >7.50x10^3 c/uL;Absolute Eosinophils, if >0.750X10^3 c/uL;Alanine Aminotransferase, 0-40 units per liter (U/L);G-Glutamyl Transferase, 0-60 U/L;Bilirubin, 0.1-1.2 milligrams per deciliter (mg/dL);Blood Urea Nitrogen, 5.9-26.0 mg/dL;Creatinine, 0.50-1.50 mg/dL;Serum Potassium, 3.5-5.5 milliequivalents per liter (mEq/L);Serum Glucose, 65-99 mg/dL;Fasting Serum Glucose, 65-99 mg/dL;Total Protein, 6.0-8.5 g/dL;Albumin, 3.5-5.5 g/dL;Urine Protein, >=4;Urine Glucose, >=4;Urine Blood, >=4;Urine Red Blood Cells >=4;Urine White Blood Cells, >=4.
Time Frame	Period A (Day 1 to Day 113)

Outcome Measure Data

Analysis Population Description

All treated participants in Period C evaluated for a specific analyte.

Arm/Group Title	Abatacept (All Participants in Period A)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses.
Overall Number of Participants Analyzed	190
Measure Type: Number; Unit of Measure: participants
Hemoglobin (Low) n=189	2
Hematocrit (Low) n=189	2
Erythrocytes (Low) n=189	1
Platelets (Low) n=189	1
Platelet Count (High) n=189	2
Leukocytes (Low) n=189	9
Leukocytes (High) n=189	10
Absolute Neutrophils + Bands (Low) n=189	5
Absolute Lymphocytes (Low) n=189	9
Absolute Eosinophils (High) n=189	16
Alanine Aminotransferase (ALT, High) n=190	2
G-Glutamyl Transferase (GGT, High) n=190	1
Bilirubin (Total, High) n=190	1
Blood Urea Nitrogen (High) n=190	6
Creatinine (High) n=190	12
Potassium (High) n=190	4
Serum Glucose (Low) n=190	26
Serum Glucose (High) n=190	2
Fasting Serum Glucose (High) n=109	1
Total Protein (High) n=190	2
Albumin (Low) n=190	2
Urine Protein (High) n=190	12
Urine Glucose (High) n=190	1
Urine Blood (High) n=190	23
Urine White Blood Cells (High) n=75	9
Urine Red Blood Cells (High) n=75	25

13. Secondary Outcome

Title	Number of Treated Participants With Marked Laboratory Abnormalities During Double-Blind Phase (Period B)
Description	Marked abnormalities were pre-defined as changes in lab tests that occurred after drug infusion and were reported relative to the normal range for each analyte. Hemoglobin, 11.6-14.8 grams per deciliter (g/dL);Hematocrit, 36.0-50.0 percent;Erythrocytes, 3.80-5.10x10*6 cells per microliter (c/uL);Platelets, 140-44 cells per liter (c/L);Leukocytes, 4.00-12.50 c/uL;Absolute Neutrophils + Bands, if <1.00x10^3 c/uL;Absolute Lymphocytes, if <0.72x10^3 or >7.50x10^3 c/uL;Absolute Eosinophils, if >0.750X10^3 c/uL;Aspartate Aminotransferase, 0-40 units per liter (U/L); Alanine Aminotransferase, 0-40 U/L;Blood Urea Nitrogen, 5.9-26.0 mg/dL;Serum Sodium, 135-148 milliequivalents per liter (mEq/L);Serum Potassium, 3.5-5.5 mEq/L;Serum Glucose, 65-99 mg/dL;Fasting Serum Glucose, 65-99 mg/dL;Urine Protein, >=4;Urine Blood, >=4;Urine Red Blood Cells >=4;Urine White Blood Cells, >=4.
Time Frame	Period B (Day 113 to Day 282)

Outcome Measure Data

Analysis Population Description

All treated participants in Period B evaluated for a specific analyte.

Arm/Group Title	Abatacept (Period B)	Placebo (Period B)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare.	Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion.
Overall Number of Participants Analyzed	60	62
Measure Type: Number; Unit of Measure: participants
Hemoglobin (Low) n=60, 61	1	1
Hematocrit (Low) n=60, 61	1	1
Erythrocytes (Low) n=60, 61	0	1
Platelets (Low) n-60, 61	4	0
Platelets (High) n=189	0	1
Leukocytes (Low) n=60, 61	1	1
Leukocytes (High) n=60, 61	1	2
Absolute Neutrophils + Bands (Low) n=60, 62	0	1
Absolute Lymphocytes (Low) n=60, 62	2	3
Absolute Eosinophils (High) n=60, 62	6	4
Aspartate Aminotransferase (AST, High) n=60, 62	1	0
Alanine Aminotransferase (ALT, High) n=60, 62	1	0
Blood Urea Nitrogen (High) n=60, 62	1	1
Serum Sodium (Low) n=60, 62	0	1
Serum Potassium (High) n=60, 62	2	0
Serum Glucose (Low) n=60, 62	4	5
Serum Glucose (High) n=60, 62	0	1
Fasting Serum Glucose (High) n=60, 62	1	1
Urine Protein (High) n=62	2	2
Urine Blood (High) n=60, 62	12	6
Urine White Blood Cells (High) n=24, 20	5	2
Urine Red Blood Cells (High) n=24, 20	6	4

14. Secondary Outcome

Title	Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Phase (Period C)
Description	Marked abnormalities were pre-defined as changes in lab tests after drug infusion and relative to normal range. Hemoglobin,11.6-14.8grams per deciliter(g/dL);Hematocrit,36.0-50.0 percent;Erythrocytes,3.80-5.10x10*6 cells per microliter(c/uL);Platelets,140-44 cells per liter(c/L);Leukocytes,4.00-12.50c/uL;Absolute(Abs)Neutrophils+Bands,<1.00x10^3 c/uL;Abs Lymphocytes,<0.72x10^3 or>7.50x10^3 c/uL;Abs Eosinophils,>0.750X10^3 c/uL;Alkaline Phosphatase,0-40 units per liter(U/L);Aspartate Aminotransferase,0-40 U/L;Alanine Aminotransferase,0-40U/L;G-Glutamyl Transferase,0-60 U/L;Bilirubin, 0.1-1.2 milligrams per deciliter(mg/dL);Blood Urea Nitrogen,5.9-26.0 mg/dL;Creatinine, 0.50-1.50mg/dL;Inorganic Phosphorus,2.8-6.2 U/L;Serum Potassium,3.5-5.5 milliequivalents per liter(mEq/L);Serum Glucose,65-99 mg/dL;Fasting Serum Glucose,65-99 mg/dL;Total Protein, 6.0-8.5 g/dL;Albumin,3.5-5.5 g/dL;Urine Protein,>=4;Urine Glucose,>=4;Urine Blood,>=4;Urine Red Blood Cells>=4;Urine White Blood Cells,>=4.
Time Frame	Period C (Day 282 to end of study)

Outcome Measure Data

Analysis Population Description

All treated participants in Period C evaluated for a specific analyte.

Arm/Group Title	Abatacept (All Participants in Period C)
Arm/Group Description:	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
Overall Number of Participants Analyzed	153
Measure Type: Number; Unit of Measure: participants
Hemoglobin (Low) n=153	12
Hematocrit (Low) n=153	8
Erythrocytes (Low) n=153	4
Platelet Count (Low) n=153	4
Platelet Count (High) n=153	5
Leukocytes (Low) n=153	20
Leukocytes (High) n=153	18
Absolute Neutrophils + Bands (Low)	14
Absolute Lymphocytes (Low) n=153	21
Absolute Lymphocytes (High) n=153	5
Absolute Eosinophils (High) n=153	50
Alkaline Phosphatase (ALP, High) n=153	2
Aspartate Aminotransferase (AST, High)	5
Alanine Aminotransferase (ALT, High) n=153	11
G-Glutamyl Transferase (GGT, High) n=153	6
Bilirubin (Total, High) n=153	3
Blood Urea Nitrogen (High) n=153	15
Creatinine (High) n=153	36
Potassium (High) n=153	10
Inorganic Phosphorus (High) n=153	4
Serum Glucose (Low) n=153	54
Serum Glucose (High) n=153	1
Fasting Serum Glucose (Low) n=100	11
Fasting Serum Glucose (High) n=100	7
Total Protein (Low) n=153	1
Total Protein (High) n=153	1
Albumin (Low) n=153	9
Urine Protein (High) n=153	35
Urine Glucose (High) n=153	1
Urine Blood (High) n=153	73
Urine White Blood Cells (High) n=117	49
Urine Red Blood Cells (High) n=117	86

15. Secondary Outcome

Title	Number of Participants With Anti-Abatacept or Anti-CTLA4 Positive Responses Over Time During Open-Label Phase (Period C)
Description	During Period C, blood samples for immunogenicity assessments were obtained just prior to the start of the IV infusion of abatacept at 3-month intervals during the first 2 years of Period C, at 6-month intervals thereafter, and again 28, 56, and 85 days after the last infusion. Direct-format, enzyme-linked immunosorbent assays (ELISAs) were used to evaluate the cytotoxic T-lymphocyte antigen 4 (CTLA4) and the anti-CTLA4-T antibody.
Time Frame	Period C (Day 282 to 85 days after the last dose of study medication)

Outcome Measure Data

Analysis Population Description

All treated participants who were evaluated for immunogenicity during Period C

Arm/Group Title	Abatacept (Period A Non-Responders in Period C)	Abatacept (Period C)	Placebo (Period B) to Abatacept (Period C)
Arm/Group Description:	Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C).	Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.	Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
Overall Number of Participants Analyzed	33	57	58
Measure Type: Number; Unit of Measure: participants
Anti-Abatacept, Overall on Treatment (n=31,54,54)	1	5	2
Anti-Abatacept, Post-Treatment (n=25,41,38)	0	3	3
Anti-CTLA4-T, Overall on Treatment (n=33,57,58)	4	4	4
Anti-CTLA4-T, Overall Post-Treatment (n=27,46,42)	4	1	1

Adverse Events

Time Frame	From first dose to last dose plus 56 days up to end of study (November 2011)
Adverse Event Reporting Description	Study initiated: February 2004; Study completed: November 2011
Arm/Group Title	Abatacept (Only Period A)	Abatacept (Period A/Period C)	Abatacept (Period A/Period B)	Abatacept (Period A)/Placebo (Period B)
Arm/Group Description	Participants treated in Period A but did not in Periods B or C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses.	Participants treated in Period A, not eligible to continue into Period B, but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C).	All participants treated with Abatacept in Periods A and B who may or may not have entered Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses, then once a month for 6 months. If participants entered Period C, treatment continued once a month for up to 5 years.	All participants treated with Abatacept in Period A, placebo in Period B, who may or may not have entered Period C. Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. If participants entered Period C, they were treated with Abatacept,10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years.
All-Cause Mortality
	Abatacept (Only Period A)	Abatacept (Period A/Period C)	Abatacept (Period A/Period B)	Abatacept (Period A)/Placebo (Period B)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events
	Abatacept (Only Period A)	Abatacept (Period A/Period C)	Abatacept (Period A/Period B)	Abatacept (Period A)/Placebo (Period B)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/32 (12.50%)	10/36 (27.78%)	9/60 (15.00%)	14/62 (22.58%)
Gastrointestinal disorders
Abdominal pain † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	0/62 (0.00%)
Vomiting † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	1/62 (1.61%)
Nausea † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
General disorders
Fatigue † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Condition aggravated † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Pyrexia † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	1/62 (1.61%)
Immune system disorders
Food allergy † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Hypersensitivity † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	0/62 (0.00%)
Infections and infestations
Erysipelas † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Abscess limb † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Appendicitis † 1	0/32 (0.00%)	0/36 (0.00%)	2/60 (3.33%)	0/62 (0.00%)
Gastroenteritis † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Herpes zoster † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Meningitis bacterial † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Tooth abscess † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	0/62 (0.00%)
Arthritis bacterial † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	1/62 (1.61%)
Dengue fever † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Pyelonephritis † 1	0/32 (0.00%)	1/36 (2.78%)	1/60 (1.67%)	0/62 (0.00%)
Varicella † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	1/62 (1.61%)
Injury, poisoning and procedural complications
Joint dislocation † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Overdose † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	0/62 (0.00%)
Multiple injuries † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Metabolism and nutrition disorders
Type 1 diabetes mellitus † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	0/62 (0.00%)
Musculoskeletal and connective tissue disorders
Arthritis † 1	0/32 (0.00%)	3/36 (8.33%)	3/60 (5.00%)	0/62 (0.00%)
Foot deformity † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	1/62 (1.61%)
Rheumatoid arthritis † 1	2/32 (6.25%)	1/36 (2.78%)	0/60 (0.00%)	1/62 (1.61%)
Torticollis † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Arthralgia † 1	0/32 (0.00%)	1/36 (2.78%)	1/60 (1.67%)	1/62 (1.61%)
Arthropathy † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Juvenile arthritis † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Synovial cyst † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	0/62 (0.00%)
Acute lymphocytic leukaemia † 1	1/32 (3.13%)	0/36 (0.00%)	0/60 (0.00%)	0/62 (0.00%)
Nervous system disorders
Encephalitis † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Temporal lobe epilepsy † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Multiple sclerosis † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Psychiatric disorders
Suicide attempt † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Reproductive system and breast disorders
Ovarian cyst † 1	1/32 (3.13%)	0/36 (0.00%)	0/60 (0.00%)	0/62 (0.00%)
Skin and subcutaneous tissue disorders
Skin ulcer † 1	0/32 (0.00%)	1/36 (2.78%)	0/60 (0.00%)	0/62 (0.00%)
Vascular disorders
Haematoma † 1	0/32 (0.00%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Abatacept (Only Period A)	Abatacept (Period A/Period C)	Abatacept (Period A/Period B)	Abatacept (Period A)/Placebo (Period B)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	22/32 (68.75%)	32/36 (88.89%)	57/60 (95.00%)	54/62 (87.10%)
Blood and lymphatic system disorders
Anaemia † 1	0/32 (0.00%)	2/36 (5.56%)	3/60 (5.00%)	5/62 (8.06%)
Leukopenia † 1	0/32 (0.00%)	3/36 (8.33%)	4/60 (6.67%)	3/62 (4.84%)
Eosinophilia † 1	0/32 (0.00%)	4/36 (11.11%)	5/60 (8.33%)	6/62 (9.68%)
Ear and labyrinth disorders
Ear pain † 1	0/32 (0.00%)	0/36 (0.00%)	1/60 (1.67%)	4/62 (6.45%)
Eye disorders
Cataract † 1	0/32 (0.00%)	2/36 (5.56%)	1/60 (1.67%)	0/62 (0.00%)
Conjunctivitis allergic † 1	0/32 (0.00%)	0/36 (0.00%)	4/60 (6.67%)	0/62 (0.00%)
Conjunctivitis † 1	0/32 (0.00%)	4/36 (11.11%)	5/60 (8.33%)	4/62 (6.45%)
Gastrointestinal disorders
Diarrhoea † 1	2/32 (6.25%)	8/36 (22.22%)	11/60 (18.33%)	15/62 (24.19%)
Mouth ulceration † 1	2/32 (6.25%)	1/36 (2.78%)	3/60 (5.00%)	4/62 (6.45%)
Abdominal discomfort † 1	0/32 (0.00%)	2/36 (5.56%)	2/60 (3.33%)	0/62 (0.00%)
Abdominal pain † 1	1/32 (3.13%)	6/36 (16.67%)	8/60 (13.33%)	8/62 (12.90%)
Abdominal pain upper † 1	0/32 (0.00%)	5/36 (13.89%)	10/60 (16.67%)	10/62 (16.13%)
Duodenitis † 1	0/32 (0.00%)	2/36 (5.56%)	0/60 (0.00%)	0/62 (0.00%)
Gastritis † 1	0/32 (0.00%)	6/36 (16.67%)	6/60 (10.00%)	5/62 (8.06%)
Vomiting † 1	2/32 (6.25%)	7/36 (19.44%)	9/60 (15.00%)	13/62 (20.97%)
Aphthous stomatitis † 1	1/32 (3.13%)	3/36 (8.33%)	3/60 (5.00%)	2/62 (3.23%)
Dyspepsia † 1	0/32 (0.00%)	1/36 (2.78%)	4/60 (6.67%)	3/62 (4.84%)
Nausea † 1	6/32 (18.75%)	5/36 (13.89%)	9/60 (15.00%)	12/62 (19.35%)
General disorders
Fatigue † 1	2/32 (6.25%)	2/36 (5.56%)	0/60 (0.00%)	1/62 (1.61%)
Chest pain † 1	0/32 (0.00%)	2/36 (5.56%)	2/60 (3.33%)	2/62 (3.23%)
Pain † 1	1/32 (3.13%)	2/36 (5.56%)	0/60 (0.00%)	2/62 (3.23%)
Chills † 1	0/32 (0.00%)	0/36 (0.00%)	3/60 (5.00%)	1/62 (1.61%)
Influenza like illness † 1	0/32 (0.00%)	0/36 (0.00%)	3/60 (5.00%)	4/62 (6.45%)
Pyrexia † 1	2/32 (6.25%)	8/36 (22.22%)	12/60 (20.00%)	12/62 (19.35%)
Infections and infestations
Pneumonia † 1	0/32 (0.00%)	2/36 (5.56%)	0/60 (0.00%)	0/62 (0.00%)
Bacteriuria † 1	0/32 (0.00%)	2/36 (5.56%)	6/60 (10.00%)	2/62 (3.23%)
Pharyngitis streptococcal † 1	2/32 (6.25%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Pharyngotonsillitis † 1	0/32 (0.00%)	2/36 (5.56%)	3/60 (5.00%)	1/62 (1.61%)
Vulvovaginitis † 1	0/32 (0.00%)	4/36 (11.11%)	1/60 (1.67%)	2/62 (3.23%)
Fungal skin infection † 1	0/32 (0.00%)	3/36 (8.33%)	3/60 (5.00%)	2/62 (3.23%)
Impetigo † 1	0/32 (0.00%)	3/36 (8.33%)	2/60 (3.33%)	2/62 (3.23%)
Pneumonia primary atypical † 1	0/32 (0.00%)	2/36 (5.56%)	0/60 (0.00%)	0/62 (0.00%)
Rhinitis † 1	0/32 (0.00%)	6/36 (16.67%)	8/60 (13.33%)	9/62 (14.52%)
Gastroenteritis † 1	1/32 (3.13%)	4/36 (11.11%)	6/60 (10.00%)	5/62 (8.06%)
Tonsillitis † 1	0/32 (0.00%)	6/36 (16.67%)	7/60 (11.67%)	3/62 (4.84%)
Upper respiratory tract infection † 1	3/32 (9.38%)	12/36 (33.33%)	11/60 (18.33%)	12/62 (19.35%)
Urinary tract infection † 1	0/32 (0.00%)	2/36 (5.56%)	10/60 (16.67%)	3/62 (4.84%)
Lice infestation † 1	0/32 (0.00%)	2/36 (5.56%)	3/60 (5.00%)	0/62 (0.00%)
Pharyngitis † 1	0/32 (0.00%)	3/36 (8.33%)	10/60 (16.67%)	13/62 (20.97%)
Nasopharyngitis † 1	3/32 (9.38%)	11/36 (30.56%)	20/60 (33.33%)	15/62 (24.19%)
Sinusitis † 1	1/32 (3.13%)	5/36 (13.89%)	12/60 (20.00%)	7/62 (11.29%)
Paronychia † 1	2/32 (6.25%)	3/36 (8.33%)	3/60 (5.00%)	2/62 (3.23%)
Tinea versicolour † 1	0/32 (0.00%)	1/36 (2.78%)	3/60 (5.00%)	1/62 (1.61%)
Varicella † 1	0/32 (0.00%)	1/36 (2.78%)	3/60 (5.00%)	3/62 (4.84%)
Viral infection † 1	3/32 (9.38%)	0/36 (0.00%)	2/60 (3.33%)	4/62 (6.45%)
Bronchitis † 1	0/32 (0.00%)	2/36 (5.56%)	8/60 (13.33%)	4/62 (6.45%)
Influenza † 1	1/32 (3.13%)	6/36 (16.67%)	16/60 (26.67%)	12/62 (19.35%)
Otitis media acute † 1	0/32 (0.00%)	2/36 (5.56%)	1/60 (1.67%)	3/62 (4.84%)
Injury, poisoning and procedural complications
Joint injury † 1	0/32 (0.00%)	1/36 (2.78%)	1/60 (1.67%)	5/62 (8.06%)
Arthropod bite † 1	0/32 (0.00%)	2/36 (5.56%)	0/60 (0.00%)	2/62 (3.23%)
Fall † 1	0/32 (0.00%)	0/36 (0.00%)	2/60 (3.33%)	5/62 (8.06%)
Investigations
Alanine aminotransferase increased † 1	0/32 (0.00%)	0/36 (0.00%)	5/60 (8.33%)	2/62 (3.23%)
Transaminases increased † 1	0/32 (0.00%)	1/36 (2.78%)	3/60 (5.00%)	1/62 (1.61%)
Aspartate aminotransferase increased † 1	0/32 (0.00%)	0/36 (0.00%)	3/60 (5.00%)	2/62 (3.23%)
Metabolism and nutrition disorders
Decreased appetite † 1	0/32 (0.00%)	2/36 (5.56%)	3/60 (5.00%)	0/62 (0.00%)
Musculoskeletal and connective tissue disorders
Myalgia † 1	0/32 (0.00%)	0/36 (0.00%)	3/60 (5.00%)	4/62 (6.45%)
Torticollis † 1	0/32 (0.00%)	2/36 (5.56%)	1/60 (1.67%)	0/62 (0.00%)
Arthralgia † 1	0/32 (0.00%)	1/36 (2.78%)	1/60 (1.67%)	4/62 (6.45%)
Back pain † 1	0/32 (0.00%)	3/36 (8.33%)	5/60 (8.33%)	2/62 (3.23%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma † 1	1/32 (3.13%)	0/36 (0.00%)	3/60 (5.00%)	4/62 (6.45%)
Nervous system disorders
Dizziness † 1	4/32 (12.50%)	3/36 (8.33%)	7/60 (11.67%)	4/62 (6.45%)
Headache † 1	7/32 (21.88%)	10/36 (27.78%)	14/60 (23.33%)	11/62 (17.74%)
Psychiatric disorders
Insomnia † 1	2/32 (6.25%)	0/36 (0.00%)	0/60 (0.00%)	1/62 (1.61%)
Renal and urinary disorders
Haematuria † 1	0/32 (0.00%)	2/36 (5.56%)	5/60 (8.33%)	4/62 (6.45%)
Dysuria † 1	0/32 (0.00%)	0/36 (0.00%)	4/60 (6.67%)	4/62 (6.45%)
Leukocyturia † 1	0/32 (0.00%)	2/36 (5.56%)	1/60 (1.67%)	0/62 (0.00%)
Reproductive system and breast disorders
Vaginal discharge † 1	0/32 (0.00%)	2/36 (5.56%)	1/60 (1.67%)	1/62 (1.61%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	4/32 (12.50%)	3/36 (8.33%)	8/60 (13.33%)	8/62 (12.90%)
Rhinitis allergic † 1	2/32 (6.25%)	1/36 (2.78%)	4/60 (6.67%)	2/62 (3.23%)
Cough † 1	4/32 (12.50%)	7/36 (19.44%)	10/60 (16.67%)	13/62 (20.97%)
Epistaxis † 1	2/32 (6.25%)	2/36 (5.56%)	0/60 (0.00%)	0/62 (0.00%)
Nasal congestion † 1	2/32 (6.25%)	0/36 (0.00%)	1/60 (1.67%)	1/62 (1.61%)
Dyspnoea † 1	0/32 (0.00%)	2/36 (5.56%)	0/60 (0.00%)	0/62 (0.00%)
Rhinorrhoea † 1	0/32 (0.00%)	2/36 (5.56%)	3/60 (5.00%)	2/62 (3.23%)
Skin and subcutaneous tissue disorders
Pruritus † 1	1/32 (3.13%)	2/36 (5.56%)	2/60 (3.33%)	1/62 (1.61%)
Eczema † 1	2/32 (6.25%)	0/36 (0.00%)	2/60 (3.33%)	4/62 (6.45%)
Rash † 1	0/32 (0.00%)	1/36 (2.78%)	3/60 (5.00%)	5/62 (8.06%)
Dermatitis † 1	0/32 (0.00%)	1/36 (2.78%)	3/60 (5.00%)	0/62 (0.00%)
Vascular disorders
Hypertension † 1	0/32 (0.00%)	2/36 (5.56%)	2/60 (3.33%)	0/62 (0.00%)
Flushing † 1	2/32 (6.25%)	0/36 (0.00%)	0/60 (0.00%)	0/62 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb
• EMail: Clinical.Trials@bms.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ruperto N, Brunner HI, Tzaribachev N, Vega-Cornejo G, Louw I, Cimaz R, Dare J, Espada G, Faugier E, Ferrandiz M, Gerloni V, Quartier P, Silva CA, Wagner-Weiner L, Gandhi Y, Passarell J, Nys M, Wong R, Martini A, Lovell DJ; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO). Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis. J Rheumatol. 2021 Jul;48(7):1073-1081. doi: 10.3899/jrheum.200154. Epub 2021 Jan 15.

Lovell DJ, Ruperto N, Mouy R, Paz E, Rubio-Perez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhaes C, Chavez-Corrales J, Huemer C, Kivitz A, Blanco FJ, Foeldvari I, Hofer M, Huppertz HI, Job Deslandre C, Minden K, Punaro M, Block AJ, Giannini EH, Martini A; Pediatric Rheumatology Collaborative Study Group and the Paediatric Rheumatology International Trials Organisation. Long-term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years. Arthritis Rheumatol. 2015 Oct;67(10):2759-70. doi: 10.1002/art.39234.

Ruperto N, Lovell DJ, Li T, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Alcala JO, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace C, Alessio M, Quartier P, Cortis E, Eberhard A, Simonini G, Lemelle I, Chalom EC, Sigal LH, Block A, Covucci A, Nys M, Martini A, Giannini EH; Paediatric Rheumatology International Trials Organisation (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1542-51. doi: 10.1002/acr.20283. Epub 2010 Jul 1.

Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhaes C, Chavez-Corrales J, Huemer C, Kivitz A, Blanco FJ, Foeldvari I, Hofer M, Horneff G, Huppertz HI, Job-Deslandre C, Loy A, Minden K, Punaro M, Nunez AF, Sigal LH, Block AJ, Nys M, Martini A, Giannini EH; Paediatric Rheumatology International Trials Organization and the Pediatric Rheumatology Collaborative Study Group. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis Rheum. 2010 Jun;62(6):1792-802. doi: 10.1002/art.27431.

Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Perez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhaes C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace CA, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH; Paediatric Rheumatology INternational Trials Organization; Pediatric Rheumatology Collaborative Study Group. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008 Aug 2;372(9636):383-91. doi: 10.1016/S0140-6736(08)60998-8. Epub 2008 Jul 14.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00095173
• Other Study ID Numbers: IM101-033
• First Submitted: November 1, 2004
• First Posted: November 2, 2004
• Results First Submitted: September 22, 2016
• Results First Posted: January 18, 2017
• Last Update Posted: January 18, 2017