Trial Outcomes & Findings for Remission and Joint Damage Progression in Early Rheumatoid Arthritis (NCT NCT00122382)
NCT ID: NCT00122382
Last Updated: 2010-11-16
Results Overview
Number of participants who achieved remission at Month 12 of treatment, as defined by a Disease Activity Score (DAS) 28-CRP score of \<2.6. DAS 28-CRP is a continuous measure, a composite of 4 variables: number of tender joints out of 28 joints, number of swollen joints out of 28 joints, CRP (in mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 (best) to 10 (worst), indicating the current activity of the rheumatoid arthritis. A DAS28 \>5.1 = high disease activity; \<=3.2 = low disease activity; \<2.6 = remission.
COMPLETED
PHASE3
1052 participants
Month 12
2010-11-16
Participant Flow
1052 participants were enrolled, 541 were not randomized (2 for adverse events, 32 subjects withdrew consent, 1 pregnancy, 6 lost to follow-up, 470 no longer met study criteria, 30 for other reasons).
Participant milestones
| Measure |
Abatacept (ABA) + Methotrexate (MTX) (Double-Blind)
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12 (end of double blind period).
|
Placebo (PLA) + Methotrexate (MTX) (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX) titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12 (end of double blind period).
|
ABA + MTX (Open-Label)
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with weekly oral MTX were administered every 28 days from Month 12 to Month 24 (open-label period).
|
|---|---|---|---|
|
Double-Blind Study
STARTED
|
256
|
255
|
0
|
|
Double-Blind Study
Treated
|
256
|
253
|
0
|
|
Double-Blind Study
COMPLETED
|
232
|
227
|
0
|
|
Double-Blind Study
NOT COMPLETED
|
24
|
28
|
0
|
|
Open-Label Study
STARTED
|
0
|
0
|
459
|
|
Open-Label Study
COMPLETED
|
0
|
0
|
433
|
|
Open-Label Study
NOT COMPLETED
|
0
|
0
|
26
|
Reasons for withdrawal
| Measure |
Abatacept (ABA) + Methotrexate (MTX) (Double-Blind)
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12 (end of double blind period).
|
Placebo (PLA) + Methotrexate (MTX) (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX) titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12 (end of double blind period).
|
ABA + MTX (Open-Label)
Participants who received ABA + MTX in the 12-month, open-label period of the study (including 232 subjects who previously received ABA + MTX and 227 subjects who previously received PLA + MTX in the 12-month, double-blind period of the study). ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with weekly oral MTX were administered every 28 days from Month 12 to Month 24 (open-label period).
|
|---|---|---|---|
|
Double-Blind Study
Adverse Event
|
9
|
11
|
0
|
|
Double-Blind Study
Death
|
2
|
2
|
0
|
|
Double-Blind Study
Lack of Efficacy
|
0
|
8
|
0
|
|
Double-Blind Study
Lost to Follow-up
|
2
|
1
|
0
|
|
Double-Blind Study
Pregnancy
|
2
|
0
|
0
|
|
Double-Blind Study
Subject No Longer Meets Study Criteria
|
1
|
0
|
0
|
|
Double-Blind Study
Withdrawal of Consent
|
7
|
3
|
0
|
|
Double-Blind Study
Protocol Violation
|
1
|
0
|
0
|
|
Double-Blind Study
Methotrexate Discontinued
|
0
|
1
|
0
|
|
Double-Blind Study
Randomized but not treated
|
0
|
2
|
0
|
|
Open-Label Study
Adverse Event
|
0
|
0
|
11
|
|
Open-Label Study
Death
|
0
|
0
|
2
|
|
Open-Label Study
Lack of Efficacy
|
0
|
0
|
3
|
|
Open-Label Study
Lost to Follow-up
|
0
|
0
|
3
|
|
Open-Label Study
Pregnancy
|
0
|
0
|
2
|
|
Open-Label Study
Poor/Non-Compliance
|
0
|
0
|
1
|
|
Open-Label Study
Withdrawal of Consent
|
0
|
0
|
4
|
Baseline Characteristics
Remission and Joint Damage Progression in Early Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=253 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
Total
n=509 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
50.1 years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
49.7 years
STANDARD_DEVIATION 13.0 • n=7 Participants
|
49.9 years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
196 Participants
n=5 Participants
|
199 Participants
n=7 Participants
|
395 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
|
Anti-Cyclic Citrullinated Peptide 2 (CCP2) Status
unknown
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Anti-Cyclic Citrullinated Peptide 2 (CCP2) Status
positive
|
236 participants
n=5 Participants
|
217 participants
n=7 Participants
|
453 participants
n=5 Participants
|
|
Anti-Cyclic Citrullinated Peptide 2 (CCP2) Status
negative
|
18 participants
n=5 Participants
|
36 participants
n=7 Participants
|
54 participants
n=5 Participants
|
|
Duration of Rheumatoid Arthritis (RA) Disease
</= 6 months
|
167 participants
n=5 Participants
|
157 participants
n=7 Participants
|
324 participants
n=5 Participants
|
|
Duration of Rheumatoid Arthritis (RA) Disease
> 6 months - 12 months
|
36 participants
n=5 Participants
|
34 participants
n=7 Participants
|
70 participants
n=5 Participants
|
|
Duration of Rheumatoid Arthritis (RA) Disease
> 12 months
|
53 participants
n=5 Participants
|
62 participants
n=7 Participants
|
115 participants
n=5 Participants
|
|
Rheumatoid Factor (RF) Status
unknown
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Rheumatoid Factor (RF) Status
positive
|
246 participants
n=5 Participants
|
245 participants
n=7 Participants
|
491 participants
n=5 Participants
|
|
Rheumatoid Factor (RF) Status
negative
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Disease Activity Scale 28 (DAS 28) C-reactive Protein (CRP)
|
6.3 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
|
6.2 units on a scale
STANDARD_DEVIATION 1.0 • n=7 Participants
|
6.3 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
|
|
Duration of RA
|
6.2 months
STANDARD_DEVIATION 7.5 • n=5 Participants
|
6.7 months
STANDARD_DEVIATION 7.1 • n=7 Participants
|
6.5 months
STANDARD_DEVIATION 7.3 • n=5 Participants
|
|
Erosion Score
|
5.4 units on a scale
STANDARD_DEVIATION 6.1 • n=5 Participants
|
4.8 units on a scale
STANDARD_DEVIATION 5.4 • n=7 Participants
|
5.1 units on a scale
STANDARD_DEVIATION 5.8 • n=5 Participants
|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI)
|
1.7 units on a scale
STANDARD_DEVIATION 0.7 • n=5 Participants
|
1.7 units on a scale
STANDARD_DEVIATION 0.7 • n=7 Participants
|
1.7 units on a scale
STANDARD_DEVIATION 0.7 • n=5 Participants
|
|
Joint Space Narrowing (JSN) Score
|
2.1 units on a scale
STANDARD_DEVIATION 4.2 • n=5 Participants
|
1.9 units on a scale
STANDARD_DEVIATION 4.0 • n=7 Participants
|
2.0 units on a scale
STANDARD_DEVIATION 4.1 • n=5 Participants
|
|
Physician Global Assessment per Visual Analogue Scale (VAS)
|
67.1 mm
STANDARD_DEVIATION 18.2 • n=5 Participants
|
65.7 mm
STANDARD_DEVIATION 18.9 • n=7 Participants
|
66.4 mm
STANDARD_DEVIATION 18.5 • n=5 Participants
|
|
Subject Global Assessment per VAS
|
65.8 mm
STANDARD_DEVIATION 21.8 • n=5 Participants
|
63.7 mm
STANDARD_DEVIATION 24.0 • n=7 Participants
|
64.8 mm
STANDARD_DEVIATION 22.9 • n=5 Participants
|
|
Subject Pain Assessment per VAS
|
66.6 mm
STANDARD_DEVIATION 22.5 • n=5 Participants
|
67.1 mm
STANDARD_DEVIATION 22.6 • n=7 Participants
|
66.8 mm
STANDARD_DEVIATION 22.5 • n=5 Participants
|
|
Swollen Joints
|
22.9 number of swollen joints
STANDARD_DEVIATION 11.3 • n=5 Participants
|
21.9 number of swollen joints
STANDARD_DEVIATION 10.1 • n=7 Participants
|
22.4 number of swollen joints
STANDARD_DEVIATION 10.8 • n=5 Participants
|
|
Tender Joints
|
31.3 number of tender joints
STANDARD_DEVIATION 14.8 • n=5 Participants
|
30.8 number of tender joints
STANDARD_DEVIATION 14.0 • n=7 Participants
|
31.0 number of tender joints
STANDARD_DEVIATION 14.4 • n=5 Participants
|
|
Total Genant-modified Sharp score
|
7.5 units on a scale
STANDARD_DEVIATION 9.7 • n=5 Participants
|
6.7 units on a scale
STANDARD_DEVIATION 8.8 • n=7 Participants
|
7.1 units on a scale
STANDARD_DEVIATION 9.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: Month 12Population: Intent to treat = all randomized and treated subjects. Those with missing data post-discontinuation were considered non-responders.
Number of participants who achieved remission at Month 12 of treatment, as defined by a Disease Activity Score (DAS) 28-CRP score of \<2.6. DAS 28-CRP is a continuous measure, a composite of 4 variables: number of tender joints out of 28 joints, number of swollen joints out of 28 joints, CRP (in mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 (best) to 10 (worst), indicating the current activity of the rheumatoid arthritis. A DAS28 \>5.1 = high disease activity; \<=3.2 = low disease activity; \<2.6 = remission.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=253 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12
|
106 participants
|
59 participants
|
PRIMARY outcome
Timeframe: Baseline, Month 12Population: The analysis was intent-to-treat. Because the analysis was change from baseline, only those with baseline and post-baseline were included. Linear extrapolation imputation was applied.
To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and joint space narrowing (JSN). The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=242 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=242 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Mean Change From Baseline in Radiographic Total Score to Month 12
Baseline Mean
|
7.50 units on a scale
Standard Deviation 9.52
|
6.67 units on a scale
Standard Deviation 8.71
|
|
Mean Change From Baseline in Radiographic Total Score to Month 12
Mean Change from Baseline
|
0.63 units on a scale
Standard Deviation 1.74
|
1.06 units on a scale
Standard Deviation 2.45
|
PRIMARY outcome
Timeframe: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.Population: All subjects who received at least 1 dose of ABA in the open-label period were included in the safety analyses.
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=459 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
AEs
|
345 participants
|
—
|
|
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Related AEs
|
128 participants
|
—
|
|
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
SAEs
|
29 participants
|
—
|
|
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Related SAEs
|
10 participants
|
—
|
|
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Discontinuations due to AEs
|
11 participants
|
—
|
|
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Discontinuations due to SAEs
|
4 participants
|
—
|
|
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
Deaths
|
2 participants
|
—
|
PRIMARY outcome
Timeframe: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.Population: All subjects who received at least 1 dose of ABA in the open-label period were included in the safety analyses.
SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=459 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Vascular disorders
|
2 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Any SAE
|
29 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Infections and infestations
|
8 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Gastrointestinal disorders
|
4 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Nervous system disorders
|
4 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Cardiac disorders
|
3 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Hepatobiliary disorders
|
3 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Eye disorders
|
2 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Musculoskeletal and connective tissue disorders
|
2 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Immune System Disorders
|
1 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Injury, Poisoning, and Procedural Complications
|
1 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Investigations
|
1 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Metabolism and Nutrition Disorders
|
1 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Renal and Urinary Disorders
|
1 participants
|
—
|
|
Number of Participants With Serious Adverse Events Reported During the Open-Label Period
Respiratory, Thoracic, and Mediastinal Disorders
|
1 participants
|
—
|
PRIMARY outcome
Timeframe: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.Population: All subjects who received at least 1 dose of ABA in the open-label period were included in the safety analyses.
Any untoward medical occurrence (SAE) that resulted in death
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=459 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With SAEs With an Outcome of Death During the Open-label Period
Pneumonia
|
1 participants
|
—
|
|
Number of Participants With SAEs With an Outcome of Death During the Open-label Period
Pneumonia/septic shock
|
1 participants
|
—
|
PRIMARY outcome
Timeframe: Double Blind Period (+56 days post last dose in double-blind period or start of open-label period, whichever came first). Open-label period (56 days post last dose in the open-label period or start of maintenance sub-study, whichever came first).Population: All subjects who received at least 1 dose of abatacept. Double-blind (DB) period: all treated in DB period; Open-label (OL) Period: all treated in OL period.
The incidence rates of autoimmune disorders are defined as the (number of patients experiencing the event/exposure within the period)\*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=459 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Incidence Rates of Autoimmune Disorders in ABA-Treated Participants
|
2.47 Number of participants/100 patient-years
|
1.30 Number of participants/100 patient-years
|
PRIMARY outcome
Timeframe: Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).Population: All subjects who received at least 1 dose of abatacept. Double-blind (DB) period: all treated in DB period; Open-label (OL) Period: all treated in OL period.
The incidence rates of infections and infestations are defined as the (number of patients experiencing the event /exposure within the period)\*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=459 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Incidence Rates of Infections and Infestations of Adverse Events in ABA-Treated Participants
|
78.37 Number of patients/100 patient-years
|
66.68 Number of patients/100 patient-years
|
PRIMARY outcome
Timeframe: Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).Population: All subjects who received at least 1 dose of abatacept. Double-blind (DB) period: all treated in DB period; Open-label (OL) Period: all treated in OL period.
The incidence rates of malignant neoplasms are defined as the (number of patients experiencing the event /exposure within the period)\*100 and are expressed in 100 person-years. Subjects experiencing the event had their exposure censored at the time of the 1st event.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=459 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Incidence Rates of Malignant Neoplasm Adverse Events in ABA-Treated Participants
|
0.81 number of patients/100 patient-years
|
0 number of patients/100 patient-years
|
PRIMARY outcome
Timeframe: Open-Label Period (Month 12 to Month 24)Population: All participants treated during the Open-Label period.
There were 107 Prespecified, acute-infusional SAEs (occurring within 1 hour after the start of study drug infusion) pre-specified in the protocol; anaphylactic shock was the only one occuring in this study.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=459 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With a Serious Acute-Infusional AE of Anaphylactic Shock During Open-Label Period
|
1 Participants
|
—
|
PRIMARY outcome
Timeframe: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.Population: All Treated participants in the Open-label Period; n=number of participants evaluated for this measure.
Number of subjects with high liver function and kinedy tests: alkaline phosphatase (ALP) \>2x upper limit of normal (ULN) or if pretreatment (PRE-RX) \>ULN then \>3x PRE-RX; aspartate aminotransferase (AST) \>3x ULN or if PRE-RX \>ULN then \>4x PRE-RX; alanine aminotransferase (ALT) \>3x ULN or if PRE-RX \>ULN then \>4x PRE-RX; g-glutamyl transferase (GGT)\>2x ULN or if PRE-RX \>ULN then \>3x PRE-RX; total bilirubin \>2x ULN or if PRE-RX \>ULN then \>4x PRE-RX; blood urea nitrogen \>2x PRE-RX; creatinine \>1.5x PRE-RX.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=459 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
ALP (n=459)
|
2 participants
|
—
|
|
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
AST (n=459)
|
10 participants
|
—
|
|
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
ALT (n=459)
|
24 participants
|
—
|
|
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
GGT (n=459)
|
15 participants
|
—
|
|
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Total Bilirubin (n=459)
|
0 participants
|
—
|
|
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Blood Urea Nitrogen (n=459)
|
13 participants
|
—
|
|
Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Creatinine (n=457)
|
81 participants
|
—
|
PRIMARY outcome
Timeframe: Continuously from start of open-label period up to 56 days post the last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.Population: All participants treated during the open-label period; n= number of participants evaluated for this measure.
Marked abnormalities in hemoglobin \>3 g/dL decrease from PRE-RX; hematocrit \<0.75x PRE-RX; erythrocytes \<0.75x PRE-RX; platelet count \<0.67x lower limit of normal (LLN) or \>1.5x ULN or if PRE-RX \<LLN then \<0.5x PRE-RX and \<100,000/mm3; leukocytes \<0.75x LLN or \>1.25x ULN or if PRE-RX \<LLN then \<0.8x PRE-RX or \>ULN if PRE-RX \>ULN then \>1.2x PRE-RX or \<LLN; neutrophils if value \<1.00 x10\^3 c/uL; lymphocytes if value \<.750 x10\^3 c/uL or if value \>7.50 x10\^3 c/uL; monocytes if value \>2000/MM3; basophils if value \>400/mm3; eosinophils if value \>.750 x10\^3 c/uL
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=459 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Low Hemoglobin (n=458)
|
9 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Low Hematocrit (n=458)
|
5 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Low Erythrocyte (n=458)
|
8 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Low Platelet Count (n=455)
|
1 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
High Platelet Count (n=455)
|
1 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Low Leukocytes (n=458)
|
14 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
High Leukocytes (n=458)
|
12 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Low Neutrophils + Bands (absolute) (n=459)
|
6 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
Low Lymphocytes (absolute) (n=459)
|
39 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
High Lymphocytes (absolute) (n=459)
|
1 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
High Monocytes (absolute) (n=459)
|
0 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
High Basophils (absolute) (n=459)
|
2 participants
|
—
|
|
Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
High Eosinophils (absolute) (n=459)
|
19 participants
|
—
|
SECONDARY outcome
Timeframe: Month 12Population: Intention-to-Treat=All randomized and treated; all missing data subsequent to discontinuation are considered non-responders.
ACR 50 response was defined as a 50% improvement from baseline to Month 12 in tender and swollen joint counts and 50% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function), and 1 acute phase reactant value \[ie, CRP\].
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=253 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With American College of Rheumatology (ACR) 50 Response at Month 12
|
147 participants
|
107 participants
|
SECONDARY outcome
Timeframe: Month 12Population: Intention-to-Treat=All randomized and treated; all missing data subsequent to discontinuation are considered non-responders.
MCR was defined as 6 months of consecutive ACR 70 response at Month 12. ACR 70, the American College of Rheumatology (ACR) definition of 70% improvement was based on a 70% improvement (compared to baseline values) in tender and swollen joint counts and 70% improvement in 3 of the remaining 5 core set measures (subject global assessment of pain, subject global assessment of disease activity, physician global assessment of disease activity, subject assessment of physical function, and 1 acute phase reactant value \[ie, CRP\]).
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=253 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Major Clinical Response (MCR) at Month 12
|
70 participants
|
30 participants
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: Last Observation Carried Forward (LOCF) Intent to Treat population = all randomized and treated. As change from baseline analysis, only those with baseline and post-baseline included.
DAS 28-CRP is a continuous variable that is a composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, CRP in milligrams/Liter (mg/L), and subject assessment of disease activity measure on a Visual Analogue Scale (VAS) of 100 millimeters (mm). The DAS28 scale=0 to 10, indicating the current activity of the rheumatoid arthritis. A DAS28 \>5.1=high disease activity; \<3.2=low disease activity; \<2.6=remission. Change from Baseline=Post-baseline - Baseline value; Adjusted for baseline value.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=253 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=251 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12
|
-3.22 units in a scale
Standard Error 0.09
|
-2.49 units in a scale
Standard Error 0.09
|
SECONDARY outcome
Timeframe: Month 12Population: Intention-to-Treat=All randomized and treated; all missing data subsequent to discontinuation are considered non-responders.
Physical function was evaluated using the HAQ-disability index (HAQ-DI), a questionnaire with 20 questions assessing function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The questions are evaluated on a 4-point scale: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). Higher scores indicate greater dysfunction. HAQ response=improvement of at least 0.3 units from baseline.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=253 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12
|
184 participants
|
157 participants
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: Last Observation Carried Forward (LOCF) Intent to Treat population = all randomized and treated. As change from baseline analysis, only those with baseline and post-baseline included.
The SF-36 covers 8 health dimensions: 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from 0 to 100, with a higher score indicating better quality of life. Two summary scores (physical and mental component summaries) were produced taking a weighted linear combination of the 8 individual subscales. Change from Baseline=Post-baseline - Baseline value; adjusted for baseline value.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=254 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=249 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
Physical Component Summary (PCS) Score
|
11.68 units on a scale
Standard Error 0.62
|
9.18 units on a scale
Standard Error 0.63
|
|
Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
Mental Component Summary (MCS) Score
|
8.15 units on a scale
Standard Error 0.64
|
6.34 units on a scale
Standard Error 0.64
|
SECONDARY outcome
Timeframe: Baseline, Month 12Population: Intention-to-Treat - linear extrapolation imputation. Analysis of change from baseline restricts subjects included in to the analysis to those with baseline and post-baseline.
To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The erosion score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). The joint space narrowing score range is 0 (no radiographic damage) to 145 (worst possible radiographic damage). Higher scores indicated more damage. Change from baseline = Post-baseline - Baseline value
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=242 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=242 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
Mean Change from Baseline in JSN Score
|
0.13 units on a scale
Standard Deviation 0.53
|
0.17 units on a scale
Standard Deviation 0.54
|
|
Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
Baseline Mean Erosion Score
|
5.48 units on a scale
Standard Deviation 6.15
|
4.81 units on a scale
Standard Deviation 5.46
|
|
Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
Mean Change from Baseline in Erosion Score
|
0.50 units on a scale
Standard Deviation 1.39
|
0.89 units on a scale
Standard Deviation 2.24
|
|
Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
Baseline Mean JSN Score
|
2.03 units on a scale
Standard Deviation 3.99
|
1.86 units on a scale
Standard Deviation 3.95
|
SECONDARY outcome
Timeframe: includes data up to approximately 85 days past the last dose of the double-blind period or start of the open-label period, whichever occurred first.Population: Treated participants in the double-blind period who were evaluated for anti-abatacept or anti-CTLA4-T responses
Serum samples were analyzed by ELISA to detect antibodies against the whole molecule (both CTLA4 and Ig \[anti-abatacept antibody\]) or solely to CTLA4 (anti-CTLA4-T antibody). Reported as titer, the reciprocal of the sample dilution which yielded a signal equivalent to the statistically set cut point for the assay. For the anti-abatacept assay, minimum required dilution is 400-fold, therefore seronegative samples are those \< lowest reportable titer (\<400). For the anti-CTLA4-T assay, minimum required dilution is 25-fold, therefore seronegative samples are those \< lowest reportable titer (\<25).
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=249 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=13 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses in the Double-blind Period as Analyzed by Enzyme-linked-immunosorbent Serologic Assay (ELISA)
Anti-abatacept Responses
|
3 Participants
|
0 Participants
|
|
Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses in the Double-blind Period as Analyzed by Enzyme-linked-immunosorbent Serologic Assay (ELISA)
Anti-CTLA4-T Responses
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Includes open-label data up to approximately 85 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.Population: Treated participants in the open-label period were evaluated for anti-abatacept or anti-CTLA4-T responses
Serum samples were analyzed by ELISA to detect antibodies against the whole molecule (both CTLA4 and Ig \[anti-abatacept antibody\]) or solely to CTLA4 (anti-CTLA4-T antibody). Reported as titer, the reciprocal of the sample dilution which yielded a signal equivalent to the statistically set cut point for the assay. For the anti-abatacept assay, minimum required dilution is 400-fold, therefore seronegative samples are those \< lowest reportable titer (\<400). For the anti-CTLA4-T assay, minimum required dilution is 25-fold, therefore seronegative samples are those \< lowest reportable titer (\<25).
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=451 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=456 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses During the Open-Label Period (From Month 12 to Month 24) as Analyzed by ELISA
|
13 participants
|
16 participants
|
SECONDARY outcome
Timeframe: Baseline, Month 24Population: All treated participants in the Open-label period. Treatment groups represent treatment received in the Double Blind Period.
Physical function was evaluated using the HAQ-disability index (HAQ-DI), a questionnaire with 20 questions assessing function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The questions are evaluated on a 4-point scale: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). Higher scores indicate greater dysfunction. HAQ response=improvement of at least 0.3 units from baseline.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=232 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=227 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 24
|
189 participants
|
178 participants
|
SECONDARY outcome
Timeframe: Baseline, Month 24Population: All treated participants in the open-label period. Because the analysis was change from baseline, only those with baseline and post-baseline were included. Linear extrapolation imputation was applied. Treatment groups represent treatment received in the double-blind period.
To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage. Change from baseline = Postbaseline - baseline value.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=213 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=192 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
Erosion Score Baseline Mean
|
5.91 units on a scale
Standard Deviation 6.48
|
5.49 units on a scale
Standard Deviation 5.85
|
|
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
Erosion Score Mean Change from Baseline
|
0.59 units on a scale
Standard Deviation 2.31
|
1.40 units on a scale
Standard Deviation 3.08
|
|
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
JSN Score Baseline Mean
|
1.83 units on a scale
Standard Deviation 3.82
|
1.75 units on a scale
Standard Deviation 3.92
|
|
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
JSN Score Mean Change from Baseline
|
0.25 units on a scale
Standard Deviation 1.03
|
0.34 units on a scale
Standard Deviation 0.99
|
|
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
Total Score Baseline Mean
|
7.73 units on a scale
Standard Deviation 9.50
|
7.24 units on a scale
Standard Deviation 8.89
|
|
Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
Total Score Mean Change from Baseline
|
0.84 units on a scale
Standard Deviation 3.22
|
1.75 units on a scale
Standard Deviation 3.59
|
SECONDARY outcome
Timeframe: Baseline, Month 24Population: All treated participants in the open-label period. Treatment groups represent treatment received in the double-blind period.
Participants with no radiographic progression (defined as change in score \<=0 or \<=0.5), from baseline to Month 24. To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=213 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=192 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Change from Baseline <= 0 in Erosion Score
|
125 Participants
|
92 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Change from Baseline <= 0.5 in Erosion Score
|
144 Participants
|
114 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Change from Baseline <= 0 in JSN Score
|
175 Participants
|
150 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Change from Baseline <= 0.5 in JSN Score
|
190 Participants
|
166 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Change from Baseline <= 0 in Total Score
|
121 Participants
|
84 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
Change from Baseline <= 0.5 in Total Score
|
139 Participants
|
107 Participants
|
SECONDARY outcome
Timeframe: Month 12, Month 24Population: Number of Participants Analyzed=All treated participants in the open-label period. (Treatment groups represent treatment received in the double-blind period.) n=the number of subjects with observed data included in the analysis.
Participants with no radiographic progression ((defined as change in score \<=0 or \<=0.5), sustained from Month 12 and Month 24. To assess joint damage progression, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=232 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=227 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
Erosion Score Sustained <=0 (n=125; n=100)
|
116 Participants
|
87 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
Erosion Score Sustained <=0.5 (n=145; n=114)
|
135 Participants
|
107 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
JSN Score Sustained <=0 (n=180; n=165)
|
169 Participants
|
150 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
JSN Score Sustained <=0.5 (n=192; n=177)
|
185 Participants
|
163 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
Total Score sustained <=0 (n=123; n=97)
|
112 Participants
|
81 Participants
|
|
Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
Total Score sustained <=0.5 (n=144; n=112)
|
131 Participants
|
101 Participants
|
SECONDARY outcome
Timeframe: Baseline, Month 12, Month 24Population: Analysis includes all treated participants in the open-label period originally randomized to abatacept. Analysis includes all participants with observed assessments collected at Baseline (Day 1), Day 365 (Month 12), and Day 729 (Month 24)
Mean difference observed in change from baseline to Month 12 and between Month 12 and Month 24 in radiographic scores (Total Score). To assess joint damage, the Genant-modified Sharp scoring method was used to evaluate radiographs of hands/wrists and feet for erosions and JSN. The total Genant-modified Sharp score ranges from 0 (no radiographic damage) to 290 (worst possible radiographic damage) and is the sum of the erosion score (range 0-145) and the joint space narrowing score (range 0-145). Higher scores indicated more damage.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=207 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=207 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Mean Difference Observed in Change From Baseline to Month 12 and Between Month 12 and Month 24 in Radiographic Scores (Total Score)
|
0.66 units on a scale
Standard Error 0.13
|
0.18 units on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.Population: All treated participants in the Double-Blind period
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. Related AE/SAE=Certain, Probable, Possible, or Missing. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=253 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Deaths
|
2 participants
|
4 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
SAEs
|
20 participants
|
20 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Related SAEs
|
5 participants
|
6 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Discontinued due to SAEs
|
3 participants
|
3 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
AEs
|
217 participants
|
211 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Related AEs
|
98 participants
|
114 participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
Discontinued due to AEs
|
8 participants
|
11 participants
|
SECONDARY outcome
Timeframe: Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.Population: All treated in the DB period. n=Number of participants evaluated for this measure.
Number of participants with laboratory values (hematology, liver and kidney functions, electrolytes, glucose tests, protein tests, metabolite tests, and urine chemistry tests) considered markedly abnormal according to prespecified protocol criteria
Outcome measures
| Measure |
ABA + MTX (Double-Blind)
n=256 Participants
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
PLA + MTX (Double-Blind)
n=253 Participants
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Hemoglobin (n=254; n=251)
|
3 participants
|
3 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Hematocrit (n=254; n=250)
|
1 participants
|
2 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Erythrocytes (n=254; n=250)
|
1 participants
|
4 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Platelet Count (n=252; n=250)
|
0 participants
|
1 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Platelet Count (n=252; n=250)
|
1 participants
|
3 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Leukocytes (n=254; n=251)
|
5 participants
|
11 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Leukocytes (n=254; n=251)
|
5 participants
|
14 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Neutrophils + Bands (absolute) (n=254; n=252)
|
2 participants
|
5 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Lymphocytes (absolute) (n=254; n=252)
|
13 participants
|
29 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Lymphocytes (absolute) (n=254; n=252)
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Monocytes (absolute) (n=254; n=252)
|
1 participants
|
1 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Basophils (absolute) (n=254; n=252)
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Eosinophils (absolute) (n=254; n=252)
|
7 participants
|
13 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Alkaline Phosphatase (n=254; n=253)
|
1 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Aspartate Aminotransferase (n=254; n=253)
|
7 participants
|
14 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Alanine Aminotransferase (n=254; n=253)
|
15 participants
|
21 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
G-Glutamyl Transferase (n=254; n=253)
|
11 participants
|
9 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Bilirubin, Total (n=254; n=253)
|
0 participants
|
2 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Blood Urea Nitrogen (n=254; n=253)
|
9 participants
|
10 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Creatinine (n=254; n=251)
|
33 participants
|
32 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Sodium, Serum (n=254; n=253)
|
0 participants
|
1 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Sodium, Serum (n=254; n=253)
|
2 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Potassium, Serum (n=254; n=251)
|
6 participants
|
3 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Potassium, Serum (n=254; n=251)
|
3 participants
|
2 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Chloride, Serum (n=254; n=253)
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Chloride, Serum (n=254; n=253)
|
1 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Calcium, Total (n=254; n=253)
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Calcium, Total (n=254; n=253)
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Phosphorus, Inorganic (n=254; n=251)
|
1 participants
|
2 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Phosphorus, Inorganic (n=254; n=251)
|
3 participants
|
3 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Glucose, Serum (n=254; n=253)
|
22 participants
|
24 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Glucose, Serum (n=254; n=253)
|
10 participants
|
13 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Protein, Total (n=254; n=253)
|
2 participants
|
0 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Protein, Total (n=254; n=253)
|
0 participants
|
1 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
Low Albumin (n=254; n=253)
|
2 participants
|
5 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Protein, Urine (n=252; n=250)
|
6 participants
|
3 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Glucose, Urine (n=252; n=250)
|
4 participants
|
6 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Blood, Urine (n=252; n=250)
|
30 participants
|
22 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Leukocyte Esterase (n=87; n=88)
|
13 participants
|
13 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Red Blood Cells, Urine (n=92; n=103)
|
30 participants
|
25 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High White Blood Cells, Urine (n=94; n=105)
|
38 participants
|
42 participants
|
|
Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
High Uric Acid (n=254; n=253)
|
1 participants
|
1 participants
|
Adverse Events
Abatacept
Placebo
Serious adverse events
| Measure |
Abatacept
n=256 participants at risk
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
Placebo
n=253 participants at risk
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Investigations
INTERNATIONAL NORMALISED RATIO INCREASED
|
0.39%
1/256
|
0.00%
0/253
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.39%
1/256
|
0.00%
0/253
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.39%
1/256
|
0.40%
1/253
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.00%
0/256
|
0.40%
1/253
|
|
Vascular disorders
HYPOTENSION
|
0.39%
1/256
|
0.00%
0/253
|
|
Psychiatric disorders
DEPRESSION
|
0.78%
2/256
|
0.00%
0/253
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.00%
0/256
|
0.40%
1/253
|
|
Hepatobiliary disorders
ACUTE HEPATIC FAILURE
|
0.00%
0/256
|
0.40%
1/253
|
|
Immune system disorders
ANAPHYLACTIC REACTION
|
0.00%
0/256
|
0.40%
1/253
|
|
Nervous system disorders
INTRACRANIAL PRESSURE INCREASED
|
0.00%
0/256
|
0.40%
1/253
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.39%
1/256
|
0.00%
0/253
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/256
|
0.40%
1/253
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.39%
1/256
|
0.00%
0/253
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.39%
1/256
|
0.00%
0/253
|
|
Infections and infestations
PNEUMONIA
|
0.39%
1/256
|
1.2%
3/253
|
|
Infections and infestations
CELLULITIS
|
0.39%
1/256
|
0.00%
0/253
|
|
Infections and infestations
GASTROENTERITIS
|
0.39%
1/256
|
0.40%
1/253
|
|
Infections and infestations
BREAST CELLULITIS
|
0.00%
0/256
|
0.40%
1/253
|
|
Infections and infestations
STAPHYLOCOCCAL INFECTION
|
0.00%
0/256
|
0.40%
1/253
|
|
Infections and infestations
LUNG INFECTION PSEUDOMONAL
|
0.39%
1/256
|
0.00%
0/253
|
|
Infections and infestations
POSTOPERATIVE WOUND INFECTION
|
0.39%
1/256
|
0.00%
0/253
|
|
Renal and urinary disorders
URETHRAL STENOSIS
|
0.00%
0/256
|
0.40%
1/253
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/256
|
0.40%
1/253
|
|
Reproductive system and breast disorders
CERVICAL DYSPLASIA
|
0.00%
0/256
|
0.40%
1/253
|
|
Injury, poisoning and procedural complications
FALL
|
0.39%
1/256
|
0.00%
0/253
|
|
Injury, poisoning and procedural complications
TIBIA FRACTURE
|
0.39%
1/256
|
0.00%
0/253
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.39%
1/256
|
0.00%
0/253
|
|
Injury, poisoning and procedural complications
SPINAL COMPRESSION FRACTURE
|
0.39%
1/256
|
0.00%
0/253
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
0.00%
0/256
|
0.40%
1/253
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.00%
0/256
|
0.40%
1/253
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.00%
0/256
|
0.40%
1/253
|
|
Musculoskeletal and connective tissue disorders
RHEUMATOID ARTHRITIS
|
0.39%
1/256
|
0.40%
1/253
|
|
Musculoskeletal and connective tissue disorders
SPINAL OSTEOARTHRITIS
|
0.00%
0/256
|
0.40%
1/253
|
|
Respiratory, thoracic and mediastinal disorders
PLEURISY
|
0.00%
0/256
|
0.40%
1/253
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.39%
1/256
|
0.00%
0/253
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.00%
0/256
|
0.40%
1/253
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/256
|
0.40%
1/253
|
|
Respiratory, thoracic and mediastinal disorders
INTERSTITIAL LUNG DISEASE
|
0.39%
1/256
|
0.00%
0/253
|
|
Respiratory, thoracic and mediastinal disorders
CRYPTOGENIC ORGANISING PNEUMONIA
|
0.39%
1/256
|
0.00%
0/253
|
|
General disorders
SUDDEN DEATH
|
0.39%
1/256
|
0.00%
0/253
|
|
General disorders
MULTI-ORGAN FAILURE
|
0.00%
0/256
|
0.40%
1/253
|
|
General disorders
INFUSION RELATED REACTION
|
0.39%
1/256
|
0.00%
0/253
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LIPOMA
|
0.39%
1/256
|
0.00%
0/253
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM SKIN
|
0.39%
1/256
|
0.00%
0/253
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PANCREATIC CARCINOMA
|
0.39%
1/256
|
0.00%
0/253
|
Other adverse events
| Measure |
Abatacept
n=256 participants at risk
ABA 10 mg/kg (weight-tiered dose) intravenous (IV) infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Study drug administered on Days 1, 15, 29 and every 28 days thereafter up to Month 12.
|
Placebo
n=253 participants at risk
Placebo (Dextrose 5% Water for Injection U.S.P. \[D5W\] or Normal Saline \[NS\] IV infusions in combination with oral MTX titrated to at least 15 mg per week not to exceed 20 mg per week. Administered on Days 1, 15, 29, and every 28 days thereafter up to Month 12.
|
|---|---|---|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
6.2%
16/256
|
5.1%
13/253
|
|
Vascular disorders
HYPERTENSION
|
6.6%
17/256
|
5.5%
14/253
|
|
Nervous system disorders
HEADACHE
|
11.7%
30/256
|
9.1%
23/253
|
|
Nervous system disorders
DIZZINESS
|
7.4%
19/256
|
5.1%
13/253
|
|
Gastrointestinal disorders
NAUSEA
|
10.2%
26/256
|
16.2%
41/253
|
|
Gastrointestinal disorders
DIARRHOEA
|
6.6%
17/256
|
9.5%
24/253
|
|
Gastrointestinal disorders
DYSPEPSIA
|
4.3%
11/256
|
5.5%
14/253
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
3.5%
9/256
|
5.9%
15/253
|
|
Infections and infestations
INFLUENZA
|
7.4%
19/256
|
9.1%
23/253
|
|
Infections and infestations
BRONCHITIS
|
7.0%
18/256
|
4.7%
12/253
|
|
Infections and infestations
NASOPHARYNGITIS
|
8.2%
21/256
|
10.3%
26/253
|
|
Infections and infestations
URINARY TRACT INFECTION
|
6.6%
17/256
|
8.7%
22/253
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
10.2%
26/256
|
10.3%
26/253
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
5.1%
13/256
|
5.5%
14/253
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
8.2%
21/256
|
6.3%
16/253
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER