Active Rheumatoid Arthritis
Conditions
Brief summary
The only trial in participants who are methotrexate-inadequate responders and have active Rheumatoid Arthritis, in which gadolinium-enhanced Magnetic Resonance Imaging; Bone Mineral Density; and biochemical markers of bone, cartilage, and synovial tissue metabolism are used to evaluate early effects (4 months) of Abatacept on inflammation/structural damage. Study will provide valuable mechanism-of-action information on how Abatacept exerts its effects (including on bone) through new techniques.
Interventions
DRUGAbatacept
Vials (250 mg/vial), intravenous (IV), 10 mg/kg, monthly infusion , 12 months of treatment
DRUGPlacebo
Intravenous (IV) bags, IV, 0 mg, monthly infusion, 12 months of treatment
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Disease activity as defined by a Disease Activity Score 28-C-Reactive Protein (CRP) \>3.2 or \>6 swollen and ≥6 tender joints and CRP greater than the upper limit of normal * At least 1 erosion in hands/wrists or positive anticyclic citrullinated peptides or rheumatoid factor * Clinically detectable synovitis of at least 1 wrist/ankle at screening and baseline * Participants must have been treated with methotrexate, on a weekly dose of at least 15 mg or a maximum tolerated dose (such as, 10 mg weekly) for at least 3 months before screening. Dose of methotrexate must be stable for at least 28 days prior to the first study dose (Day 1)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Period: Mean Synovitis Scores at Baseline As Measured by the Rheumatoid Arthritis Clinical Trials 6 (OMERACT 6) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) | At baseline | Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis = Follow-up synovitis score - baseline score. |
| Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Planned Analysis Using Non-Parametric ANCOVA | Baseline to Day 113 | Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis=Follow-up synovitis score-baseline score. |
| Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Post Hoc Sensitivity Analysis Using Parametric ANCOVA Analysis | Baseline to Day 113 | Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis score=Follow-up synovitis score-baseline synovitis score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Period: Adjusted Mean Change From Baseline in Osteitis OMERACT 6 Scores | Baseline to Day 113 | Osteitis assessed at 23 anatomic locations: 15 in 1 wrist and 8 in attached. Each site scored in 1.0 increments, indicating involvement of original articular bone (0=none to 3=severe). Total score for hands/wrists is sum of scores for each location. Maximum score per hand/wrist is 23 (total anatomic locations)\*3 (maximum score per joint)=69. Minimum score=0(normal). Increasing score=greater severity. Adjusted mean change from baseline in osteitis score=mean score at Day 113-mean score at baseline. Adjustment based on ANCOVA model with treatment=factor and baseline value=covariate. |
| Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | Baseline to Day 113 | Bone erosion and osteitis were assessed at a total of 23 anatomic locations according to erosion (for bone erosion) or involvement (for osteitis) of the original articular bone. Synovitis assessed as above-normal post-gadolinium enhancement in 3 wrist regions: distal radioulnar joint, radiocarpal joint, and intercarpal and carpometacarpal joints. |
| Double-blind Period: Baseline Mean RAMRIS Scores | Baseline | RAMRIS score is the sum of its core components: Synovitis Score, Osteitis Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Osteitis scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score + Osteitis Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Osteitis Score, Erosion Score, and RAMRIS score, increasing number=increasing severity. |
| Double-blind Period: Adjusted Mean Change From Baseline in RAMRIS Scores | Baseline to Day 113 | RAMRIS Score=sum of core components: Synovitis (S), Osteitis (O), and Erosion (E) Scores. S scored 0 (none) to 9 (maximum distension of synovial cavity); O scored 0 (none) to 69 (maximum articular bone involvement); E scored 0 (none) to 230 (maximum erosion of articular bone). RAMRIS=S+O+E Scores. RAMRIS minimum score=0 (normal), maximum=308 (severe structural damage). Adjusted change from baseline in RAMRIS=mean RAMRIS at Day 113-mean RAMRIS at baseline. Adjustment based on ANCOVA model: treatment=factor, baseline value=covariate. |
| Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Baseline to Days 15, 29, 57, 85, and 113 | PINP and osteocalcin are markers of bone formation. Osteocalcin is synthesized by osteoblasts and is associated with osteoblast synthetic activity. Osteoblasts secrete type 1 procollagen, and cleavage of large fragments from the carboxy and amino terminal ends result in formation of mature type 1 collagen and production of PINP fragments. |
| Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Baseline to Days 15, 29, 57, 85, and 113 | CTX-I and ICTP are biochemical markers of bone resorption or bone degradation |
| Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Baseline to Days 15, 29, 57, 85, and 113 | Urinary CTX-II is a biochemical marker of type II collagen breakdown. In participants with early rheumatoid arthritis, increased levels of CTX-II can be predictive of rapid radiographic progression over periods of 1 to 5 years. These markers of cartilage destruction can predict progression of joint damage, independent of clinical and biologic indices of disease activity and baseline joint damage. |
| Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Baseline to Days 15, 29, 57, 85, and 113 | Glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) is a specific biochemical marker reflecting the degradation of the synovial tissue membrane. It is a glycosylated derivative of the collagen crosslink pyridinoline, and it is present in significant amounts only in the synovial membrane; it is absent from bone and present in minutes amounts in cartilage and other soft tissues. Increased urinary levels of Glc-Gal-PYD have been found in early and long-standing rheumatoid arthritis, high levels being associated with rapid destruction. |
| Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment. |
| Double-blind Period: Baseline Mean Erosion OMERACT 6 Scores | At baseline | Bone erosion assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 (no damage) to 10 (severe damage) according to erosion of the original articular bone (each unit=10% loss of articular bone). The total erosion score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 230. Increasing score=greater severity. |
| Double-blind Period: Number of Participants With Infections/Infestations of Special Interest | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | Infections/Infestations of Special Interest are AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment. |
| Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | Acute infusional AEs are AEs with onset during the first hour after the start of study drug infusion. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs considered possibly, probably, or certainly related to study treatment were graded according to Common Terminology Criteria for Adverse Events ,Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). |
| Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | Peri-infusional AEs are AEs occurring during the first 24 hours after the start of study drug infusion. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs considered possibly, probably, or certainly related to study treatment were graded according to Common Terminology Criteria for Adverse Events, Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). |
| Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | BL=baseline; LLN=lower limit of normal; ULN=upper limit of normal. Marked abnormality criteria: Hemoglobin: \>3 g/dL decrease from BL. Hematocrit: \<0.75\*BL. Erythrocytes: \<0.75\*BL. Platelets: \<0.67\*LLN/\>1.5\*ULN, or if BL \<LLN, use 0.5\*BL/\<100,000 mm\^3. Leukocytes: \<0.75\*LLN/\>1.25\*ULN, or if BL\<LLN, use \<0.8\*BL/\>ULN, or if BL\>ULN, use \>1.2\*BL/\<LLN. Neutrophils+bands: \<1.0\*10\^3 c/uL. Eosinophils: \>0.750\*10\^3 c/uL. Basophils: \> 400 mm\^3. Monocytes: \>2000 mm\^3. Lymphocytes: \<0.750\*10\^3 c/uL/\>7.50\*10\^3 c/uL. |
| Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | From Day 1 to Day 113, and including up to 56 days post last dose of double-blind period, or start of first dose of open-label period | ULN=upper limit of normal; BL=baseline. Marked abnormality criteria: Alkaline phosphatase: \>2\*ULN, or if BL\>ULN, use \>3\*BL; aspartate aminotransferase: \>3\*ULN, or if BL\>ULN,use \>4\*BL; alanine aminotransferase: \>3\*ULN, or if BL\>ULN, use \>4\*BL; G-Glutamyl transferase: \>2\*ULN, or if BL\>ULN, use \>3\*BL; Bilirubin: \>2\*ULN, or if BL\>ULN, use \>4\*BL; blood urea nitrogen: \>2\*BL; creatinine: \>1.5\*BL. |
| Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Marked abnormality: Sodium: \<0.95\*LLN/\>1.05\*ULN,or if BL\<LLN, use 0.95\*BL or \>ULN,or if BL\>ULN, use\>1.05\*BL or \<LLN. Potassium: \<0.9\*LLN/\>1.1\* ULN,or if BL\<LLN, use 0.9\*BL or \>ULN, or if BL\>ULN, use\>1.1\*BL or \<LLN. Chloride: \<0.9\*LLN/\>1.1\*ULN, or if BL\<LLN, use 0.9\*BL or \>ULN, or if BL\>ULN, use\>1.1\*BL or \<LLN. Calcium: \<0.8\*LLN/\>1.2\*ULN, or if BL\<LLN, use 0.75\*BL or \>ULN, or if BL\>ULN, use\>1.25\*BL or \<LLN. Phosphorous: \<0.75\*LLN/\>1.25\*ULN, or if BL\<LLN, use 0.67\*BL or \>ULN, or if BL\>ULN, use\>1.33\*BL or \<LLN. |
| Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | LLN=lower limit of normal; ULN=upper limit of normal; BL-baseline. Marked abnormality c: serum glucose:\<65 mg/dL/\>220 mg/dL; fasting serum glucose: \<0.8\* LLN/\>1.5\* ULN, or if BL\<LLN, use 0.8\*BL or \>ULN, or if BL\>ULN, use \>2.0\*BL or \<LLN; total protein: \<0.9\*LLN/\>1.1\* ULN; albumin: \<0.9\*LLN,or if BL\<LLN, use \<0.75 BL; uric acid: \>1.5\* ULN, or if BL\>ULN, use \>2\*BL. Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, red blood cells, white blood cells):Use ≥2 when BL value missing or value ≥4,or when predose=0 or 0.5. Use ≥3 when predose=1. Use ≥4 when predose=2 or 3 |
| Double-blind Period:Number of Participants With Significantly Abnormal Changes in Vital Signs | Days 1, 15, 29, 57, 85, and 113 | Vital signs, which included blood pressure, heart rate, respiration, and temperature, were monitored predose and 1 hour after start of infusion. Changes in vital signs were determined to be significantly abnormal at the discretion of the investigator but were generally those that either exceeded, or failed to reach, normal parameters. Normal vital sign parameter ranges varied by site. |
| Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay | Day 1 to Day 113 | On-Rx=on treatment; post-Rx=post treatment. ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1. |
| Double-blind Period: Number of Participants With AEs of Special Interest | From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period | An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including serious, opportunistic, and all other infections; autoimmune disorders; neoplasms; acute infusional AEs (prespecified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (prespecified AEs occurring within 24 hours of start of infusion). |
| Double-blind Period: Adjusted Mean Change From Baseline in Erosion OMERACT 6 Scores | Baseline to Day 113 | Bone erosion assessed at 23 anatomic locations: 15 in 1 wrist and 8 in attached hand. Each site is scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. Total erosion score for hands/wrists is sum of the individual scores for each location. Thus the maximum score per hand/wrist is 230. Increasing score=greater severity. Adjusted change from baseline in erosion score=mean score at Day 113-mean erosion score at baseline. Adjustment based on ANCOVA model with treatment=factor and baseline value=covariate. |
| Double-blind Period: Baseline Mean Osteitis OMERACT 6 Scores | At baseline | Osteitis assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 to 3, indicating involvement of original articular bone. The total score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 23 (total number of anatomic locations) \* 3 (maximum per joint)=69. Minimum score=0, indicating normal. Increasing score=greater severity. |
Countries
Belgium, Germany, Netherlands, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abatacept (ABA) + Methotrexate (MTX) Abatacept was administered IV on Day 1, 15, 29 and every 28 days up to and including Day 113.Abatacept was given as a dose based on body weight: 500 mg for participants weighing \< 60 kg, 750 mg for participants weighing 60 to 100 kg and 1 gram for participants weighing \> 100 kg. | 27 |
| Placebo (PLA) + MTX PLA was administered IV on Day 1, 15, 29 and every 28 days up to and including Day 113. In addition, participants received a weekly dose of MTX of at least 15 mg or a maximum tolerated dose (ie, 10 mg weekly) | 23 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Participant no longer met study criteria | 1 | 0 |
Baseline characteristics
| Characteristic | Abatacept (ABA) + Methotrexate (MTX) | Total | Placebo (PLA) + MTX |
|---|---|---|---|
| Age Continuous | 51.7 years STANDARD_DEVIATION 11.2 | 52.1 years STANDARD_DEVIATION 11.2 | 52.5 years STANDARD_DEVIATION 11.5 |
| Anti-CCP2 Status Negative | 14 participants | 20 participants | 6 participants |
| Anti-CCP2 Status Positive | 13 participants | 30 participants | 17 participants |
| Cross Classification of RF Status and CCP2 Status at Baseline RF negative, anti-CCP2 negative | 12 participants | 15 participants | 3 participants |
| Cross Classification of RF Status and CCP2 Status at Baseline RF negative, anti-CCP2 positive | 0 participants | 1 participants | 1 participants |
| Cross Classification of RF Status and CCP2 Status at Baseline RF positive, anti-CCP2 negative | 2 participants | 5 participants | 3 participants |
| Cross Classification of RF Status and CCP2 Status at Baseline RF positive, anti-CCP2 positive | 13 participants | 29 participants | 16 participants |
| Disease Activity Score (DAS) 28 (C-Reactive Protein [CRP]) | 5.3 units on a scale STANDARD_DEVIATION 1.1 | 5.3 units on a scale STANDARD_DEVIATION 1 | 5.3 units on a scale STANDARD_DEVIATION 0.9 |
| Duration of Rheumatoid Arthritis | 25.7 months STANDARD_DEVIATION 18 | 26.8 months STANDARD_DEVIATION 17.4 | 28.2 months STANDARD_DEVIATION 17 |
| Number of Swollen Joints | 11.3 joints STANDARD_DEVIATION 6.6 | 10.0 joints STANDARD_DEVIATION 5.7 | 8.5 joints STANDARD_DEVIATION 4.1 |
| Number of Tender Joints | 12.9 joints STANDARD_DEVIATION 7.1 | 13.1 joints STANDARD_DEVIATION 7.2 | 13.3 joints STANDARD_DEVIATION 7.2 |
| Region of Enrollment Belgium | 9 participants | 16 participants | 7 participants |
| Region of Enrollment Germany | 10 participants | 16 participants | 6 participants |
| Region of Enrollment Netherlands | 3 participants | 7 participants | 4 participants |
| Region of Enrollment Spain | 2 participants | 4 participants | 2 participants |
| Region of Enrollment Sweden | 2 participants | 5 participants | 3 participants |
| Region of Enrollment United Kingdom | 1 participants | 2 participants | 1 participants |
| Rheumatoid Factor (RF) Status Negative | 12 participants | 16 participants | 4 participants |
| Rheumatoid Factor (RF) Status Positive | 15 participants | 34 participants | 19 participants |
| Sex: Female, Male Female | 16 Participants | 32 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 27 | 8 / 23 |
| serious Total, serious adverse events | 0 / 27 | 2 / 23 |
Outcome results
Primary
Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Planned Analysis Using Non-Parametric ANCOVA
Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis=Follow-up synovitis score-baseline score.
Time frame: Baseline to Day 113
Population: All randomized participants who received at least 1 dose of study medication and had wrist synovitis assessments available at baseline and Day 113.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Planned Analysis Using Non-Parametric ANCOVA | -0.44 units on a scale | Standard Deviation 1.47 |
| Placebo + Methotrexate | Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Planned Analysis Using Non-Parametric ANCOVA | 0.52 units on a scale | Standard Deviation 1.38 |
Comparison: Comparison in change from baseline of wrist synovitis using OMERACT 6 rheumatoid arthritis magnetic resonance imaging score method between abatacept and placebo at Day 113 based on a nonparametric analysis of covariance model. Baseline and changes from baseline of the total wrist synovitis scores were ranked, and the model included the rank score for change from baseline as the dependent variable with treatment group as a main effect and the rank score for baseline as an additional covariate.p-value: 0.103ANCOVA
Primary
Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Post Hoc Sensitivity Analysis Using Parametric ANCOVA Analysis
Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis score=Follow-up synovitis score-baseline synovitis score.
Time frame: Baseline to Day 113
Population: All randomized participants who received at least 1 dose of study medication and who had wrist synovitis assessments available at baseline and Day 113.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Post Hoc Sensitivity Analysis Using Parametric ANCOVA Analysis | -0.31 units on a scale | Standard Deviation 0.26 |
| Placebo + Methotrexate | Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Post Hoc Sensitivity Analysis Using Parametric ANCOVA Analysis | 0.38 units on a scale | Standard Deviation 0.27 |
Comparison: Comparison in change from baseline of wrist synovitis using OMERACT 6 rheumatoid arthritis magnetic resonance imaging (MRI) score method between ABA and PLA at Day 113 based on a parametric analysis of covariance model (ANCOVA). The model included the score change from baseline as the dependent variable, treatment group as a main effect and baseline score as an additional covariate.p-value: 0.078ANCOVA
Primary
Double-blind Period: Mean Synovitis Scores at Baseline As Measured by the Rheumatoid Arthritis Clinical Trials 6 (OMERACT 6) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS)
Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis = Follow-up synovitis score - baseline score.
Time frame: At baseline
Population: All randomized participants who received at least 1 dose of study medication and had synovitis assessments available at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Mean Synovitis Scores at Baseline As Measured by the Rheumatoid Arthritis Clinical Trials 6 (OMERACT 6) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) | 4.48 units on a scale | Standard Deviation 2.1 |
| Placebo + Methotrexate | Double-blind Period: Mean Synovitis Scores at Baseline As Measured by the Rheumatoid Arthritis Clinical Trials 6 (OMERACT 6) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) | 3.52 units on a scale | Standard Deviation 2.43 |
Secondary
Double-blind Period: Adjusted Mean Change From Baseline in Erosion OMERACT 6 Scores
Bone erosion assessed at 23 anatomic locations: 15 in 1 wrist and 8 in attached hand. Each site is scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. Total erosion score for hands/wrists is sum of the individual scores for each location. Thus the maximum score per hand/wrist is 230. Increasing score=greater severity. Adjusted change from baseline in erosion score=mean score at Day 113-mean erosion score at baseline. Adjustment based on ANCOVA model with treatment=factor and baseline value=covariate.
Time frame: Baseline to Day 113
Population: All randomized participants who received at least 1 dose of study medication and had erosion OMERACT 6 assessments available at baseline and Day 113.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Adjusted Mean Change From Baseline in Erosion OMERACT 6 Scores | 0.45 units on a scale | Standard Deviation 0.43 |
| Placebo + Methotrexate | Double-blind Period: Adjusted Mean Change From Baseline in Erosion OMERACT 6 Scores | 0.95 units on a scale | Standard Deviation 0.45 |
Comparison: Comparison in the change from baseline of erosion score using the OMERACT 6 RA MRI score method between Abatacept and Placebo at Day 113 was based on a non-parametric analysis of covariance model (ANCOVA). Change from BL = Post-BL measurement-BL value. Adjustment was based on ANCOVA model with treatment as a factor and BL value a covariate.95% CI: [-1.77, 0.76]ANCOVA
Secondary
Double-blind Period: Adjusted Mean Change From Baseline in Osteitis OMERACT 6 Scores
Osteitis assessed at 23 anatomic locations: 15 in 1 wrist and 8 in attached. Each site scored in 1.0 increments, indicating involvement of original articular bone (0=none to 3=severe). Total score for hands/wrists is sum of scores for each location. Maximum score per hand/wrist is 23 (total anatomic locations)\*3 (maximum score per joint)=69. Minimum score=0(normal). Increasing score=greater severity. Adjusted mean change from baseline in osteitis score=mean score at Day 113-mean score at baseline. Adjustment based on ANCOVA model with treatment=factor and baseline value=covariate.
Time frame: Baseline to Day 113
Population: All randomized participants who received at least 1 dose of study medication and had osteitis OMERACT 6 assessments available at baseline and Day 113.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Adjusted Mean Change From Baseline in Osteitis OMERACT 6 Scores | -1.94 units on a scale | Standard Deviation 0.86 |
| Placebo + Methotrexate | Double-blind Period: Adjusted Mean Change From Baseline in Osteitis OMERACT 6 Scores | 1.54 units on a scale | Standard Deviation 0.9 |
Comparison: Comparison in the change from baseline of Edema/Osteitis score using the OMERACT 6 RA MRI score method between Abatacept and Placebo at Day 113 was based on a non-parametric analysis of covariance model (ANCOVA). Change from BL = Post-BL measurement-BL value. Adjustment was based on ANCOVA model with treatment as a factor and BL value a covariate.95% CI: [-6, -0.96]ANCOVA
Secondary
Double-blind Period: Adjusted Mean Change From Baseline in RAMRIS Scores
RAMRIS Score=sum of core components: Synovitis (S), Osteitis (O), and Erosion (E) Scores. S scored 0 (none) to 9 (maximum distension of synovial cavity); O scored 0 (none) to 69 (maximum articular bone involvement); E scored 0 (none) to 230 (maximum erosion of articular bone). RAMRIS=S+O+E Scores. RAMRIS minimum score=0 (normal), maximum=308 (severe structural damage). Adjusted change from baseline in RAMRIS=mean RAMRIS at Day 113-mean RAMRIS at baseline. Adjustment based on ANCOVA model: treatment=factor, baseline value=covariate.
Time frame: Baseline to Day 113
Population: All randomized participants who received at least 1 dose of study medication and had RAMRIS assessments available at baseline and Day 113.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Adjusted Mean Change From Baseline in RAMRIS Scores | -1.82 units on a scale | Standard Deviation 1.13 |
| Placebo + Methotrexate | Double-blind Period: Adjusted Mean Change From Baseline in RAMRIS Scores | 2.89 units on a scale | Standard Deviation 1.18 |
Comparison: Comparison in the change from baseline of RAMRIS score using the OMERACT 6 RA MRI score method between Abatacept and Placebo at Day 113 was based on a non-parametric analysis of covariance model (ANCOVA). Change from BL = Post-BL measurement-BL value. Adjustment was based on ANCOVA model with treatment as a factor and BL value a covariate.95% CI: [-8, -1.42]ANCOVA
Secondary
Double-blind Period: Baseline Mean Erosion OMERACT 6 Scores
Bone erosion assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 (no damage) to 10 (severe damage) according to erosion of the original articular bone (each unit=10% loss of articular bone). The total erosion score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 230. Increasing score=greater severity.
Time frame: At baseline
Population: All randomized participants who received at least 1 dose of study medication and had erosion OMERACT 6 assessments available at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Baseline Mean Erosion OMERACT 6 Scores | 12.60 units on a scale | Standard Deviation 9.41 |
| Placebo + Methotrexate | Double-blind Period: Baseline Mean Erosion OMERACT 6 Scores | 9.65 units on a scale | Standard Deviation 10.11 |
Secondary
Double-blind Period: Baseline Mean Osteitis OMERACT 6 Scores
Osteitis assessed at a total of 23 anatomic locations: 15 in 1 wrist and 8 in the hand of the same side. Each site is scored in 1.0 increments from 0 to 3, indicating involvement of original articular bone. The total score for the hands/wrists is the sum of the individual scores for each location. Thus the maximum score achievable per hand/wrist is 23 (total number of anatomic locations) \* 3 (maximum per joint)=69. Minimum score=0, indicating normal. Increasing score=greater severity.
Time frame: At baseline
Population: All randomized participants who received at least 1 dose of study medication and had osteitis OMERACT 6 assessments available at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Baseline Mean Osteitis OMERACT 6 Scores | 7.72 units on a scale | Standard Deviation 7.04 |
| Placebo + Methotrexate | Double-blind Period: Baseline Mean Osteitis OMERACT 6 Scores | 8.00 units on a scale | Standard Deviation 9.72 |
Secondary
Double-blind Period: Baseline Mean RAMRIS Scores
RAMRIS score is the sum of its core components: Synovitis Score, Osteitis Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Osteitis scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score + Osteitis Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Osteitis Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.
Time frame: Baseline
Population: All randomized participants who received at least 1 dose of study medication and had RAMRIS assessments available at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Baseline Mean RAMRIS Scores | 24.80 units on a scale | Standard Deviation 16.36 |
| Placebo + Methotrexate | Double-blind Period: Baseline Mean RAMRIS Scores | 21.17 units on a scale | Standard Deviation 20.45 |
Secondary
Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C])
Urinary CTX-II is a biochemical marker of type II collagen breakdown. In participants with early rheumatoid arthritis, increased levels of CTX-II can be predictive of rapid radiographic progression over periods of 1 to 5 years. These markers of cartilage destruction can predict progression of joint damage, independent of clinical and biologic indices of disease activity and baseline joint damage.
Time frame: Baseline to Days 15, 29, 57, 85, and 113
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 29 UCTX2C (n=21, n=19) | -3.40 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 85 UCTX2C (n=22, n=20) | -10.83 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 57 UCTX2C (n=23, n=19) | 0.24 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 113 UCTX2C (n=22, n=20) | -18.49 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 15 UCTX2C (n=24, n=21) | -8.51 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 113 UCTX2C (n=22, n=20) | 9.86 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 15 UCTX2C (n=24, n=21) | 5.14 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 29 UCTX2C (n=21, n=19) | 6.81 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 57 UCTX2C (n=23, n=19) | 5.43 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C]) | Day 85 UCTX2C (n=22, n=20) | 9.67 percent change |
Secondary
Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC])
Glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) is a specific biochemical marker reflecting the degradation of the synovial tissue membrane. It is a glycosylated derivative of the collagen crosslink pyridinoline, and it is present in significant amounts only in the synovial membrane; it is absent from bone and present in minutes amounts in cartilage and other soft tissues. Increased urinary levels of Glc-Gal-PYD have been found in early and long-standing rheumatoid arthritis, high levels being associated with rapid destruction.
Time frame: Baseline to Days 15, 29, 57, 85, and 113
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 29 UGGPC (n=22, n=18) | -1.83 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 85 UGGPC (n=22, n=18) | 0.32 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 57 UGGPC (n=23, n=16) | 1.58 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 113 UGGPC (n=22, n=18) | -12.16 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 15 UGGPC (n=24, n=20) | 4.44 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 113 UGGPC (n=22, n=18) | -3.10 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 15 UGGPC (n=24, n=20) | -3.84 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 29 UGGPC (n=22, n=18) | -3.19 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 57 UGGPC (n=23, n=16) | 5.73 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC]) | Day 85 UGGPC (n=22, n=18) | 16.29 percent change |
Secondary
Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP])
CTX-I and ICTP are biochemical markers of bone resorption or bone degradation
Time frame: Baseline to Days 15, 29, 57, 85, and 113
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 15 ICTP (n=25, n=21) | -5.56 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 85 CTX-1 (n=24, n=21) | -6.94 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 29 ICTP (n=26, n=21) | -3.47 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 85 ICTP (n=24, n=21) | -6.36 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 29 CTX-1 (n=26, n=21) | 0.48 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 113 CTX-1 (n=24, n=21) | -7.23 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 57 CTX-1 (n=25, n=21) | 15.13 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 113 ICTP (n=24, n=21) | -11.29 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 57 ICTP (n=25, n=21) | -5.08 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 15 CTX-1 (n=25, n=21) | 1.65 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 57 CTX-1 (n=25, n=21) | 7.02 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 15 CTX-1 (n=25, n=21) | -6.37 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 15 ICTP (n=25, n=21) | 6.25 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 29 CTX-1 (n=26, n=21) | -0.72 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 29 ICTP (n=26, n=21) | 4.34 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 57 ICTP (n=25, n=21) | 8.73 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 85 CTX-1 (n=24, n=21) | 15.65 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 85 ICTP (n=24, n=21) | 2.25 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 113 CTX-1 (n=24, n=21) | 0.00 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP]) | Day 113 ICTP (n=24, n=21) | 11.64 percent change |
Secondary
Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP)
PINP and osteocalcin are markers of bone formation. Osteocalcin is synthesized by osteoblasts and is associated with osteoblast synthetic activity. Osteoblasts secrete type 1 procollagen, and cleavage of large fragments from the carboxy and amino terminal ends result in formation of mature type 1 collagen and production of PINP fragments.
Time frame: Baseline to Days 15, 29, 57, 85, and 113
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 15 osteocalcin (n=25, n=21) | 1.82 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 15 serum intact PINP (n=25, n=21) | 6.83 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 29 osteocalcin (n=26, n=21) | 2.43 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 29 serum intact PINP (n=26, n=21) | 11.62 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 57 osteocalcin (n=25, n=21) | 4.02 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 57 serum intact PINP (n=25, n=21) | 3.68 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 85 osteocalcin (n=24, n=21) | 4.76 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 85 serum intact PINP (n=24, n=21) | 5.97 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 113 osteocalcin (n=24, n=21) | 3.18 percent change |
| Abatacept + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 113 serum intact PINP (n=24, n=21) | 2.98 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 85 serum intact PINP (n=24, n=21) | -7.23 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 15 osteocalcin (n=25, n=21) | 4.41 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 57 serum intact PINP (n=25, n=21) | 12.18 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 15 serum intact PINP (n=25, n=21) | 3.94 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 113 serum intact PINP (n=24, n=21) | 4.75 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 29 osteocalcin (n=26, n=21) | 12.14 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 85 osteocalcin (n=24, n=21) | 10.62 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 29 serum intact PINP (n=26, n=21) | -0.18 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 113 osteocalcin (n=24, n=21) | 7.87 percent change |
| Placebo + Methotrexate | Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP) | Day 57 osteocalcin (n=25, n=21) | 10.53 percent change |
Secondary
Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest
Acute infusional AEs are AEs with onset during the first hour after the start of study drug infusion. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs considered possibly, probably, or certainly related to study treatment were graded according to Common Terminology Criteria for Adverse Events ,Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 overdose | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 diarrhea | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 headache | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 flushing | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 flushing | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 headache | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 diarrhea | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest | Grade 1 overdose | 1 participants |
Secondary
Double-blind Period: Number of Participants With AEs of Special Interest
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including serious, opportunistic, and all other infections; autoimmune disorders; neoplasms; acute infusional AEs (prespecified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (prespecified AEs occurring within 24 hours of start of infusion).
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Malignancies | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Acute infusional AEs | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Autoimmune disorders | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Peri-infusional AEs | 4 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Infections | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Peri-infusional AEs | 5 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Infections | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Malignancies | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Autoimmune disorders | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With AEs of Special Interest | Acute infusional AEs | 4 participants |
Secondary
Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | Deaths | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | SAEs | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | Treatment-related SAEs | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | SAEs Leading to Discontinuation | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | AEs | 20 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | Treatment-related AEs | 8 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | AEs Leading to Discontinuation | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | SAEs Leading to Discontinuation | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | Deaths | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | Treatment-related AEs | 6 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | SAEs | 2 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | AEs | 14 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation | Treatment-related SAEs | 0 participants |
Secondary
Double-blind Period: Number of Participants With Infections/Infestations of Special Interest
Infections/Infestations of Special Interest are AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death). AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment.
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Infections/Infestations of Special Interest | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Infections/Infestations of Special Interest | 0 participants |
Secondary
Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality
LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Marked abnormality: Sodium: \<0.95\*LLN/\>1.05\*ULN,or if BL\<LLN, use 0.95\*BL or \>ULN,or if BL\>ULN, use\>1.05\*BL or \<LLN. Potassium: \<0.9\*LLN/\>1.1\* ULN,or if BL\<LLN, use 0.9\*BL or \>ULN, or if BL\>ULN, use\>1.1\*BL or \<LLN. Chloride: \<0.9\*LLN/\>1.1\*ULN, or if BL\<LLN, use 0.9\*BL or \>ULN, or if BL\>ULN, use\>1.1\*BL or \<LLN. Calcium: \<0.8\*LLN/\>1.2\*ULN, or if BL\<LLN, use 0.75\*BL or \>ULN, or if BL\>ULN, use\>1.25\*BL or \<LLN. Phosphorous: \<0.75\*LLN/\>1.25\*ULN, or if BL\<LLN, use 0.67\*BL or \>ULN, or if BL\>ULN, use\>1.33\*BL or \<LLN.
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low sodium | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High sodium | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low potassium | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High potassium | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low chloride | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High chloride | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low calcium | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High calcium | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low phosphorous | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High phosphorous | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High calcium | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low sodium | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High chloride | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High sodium | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High phosphorous | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low potassium | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low calcium | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | High potassium | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low phosphorous | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality | Low chloride | 0 participants |
Secondary
Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality
ULN=upper limit of normal; BL=baseline. Marked abnormality criteria: Alkaline phosphatase: \>2\*ULN, or if BL\>ULN, use \>3\*BL; aspartate aminotransferase: \>3\*ULN, or if BL\>ULN,use \>4\*BL; alanine aminotransferase: \>3\*ULN, or if BL\>ULN, use \>4\*BL; G-Glutamyl transferase: \>2\*ULN, or if BL\>ULN, use \>3\*BL; Bilirubin: \>2\*ULN, or if BL\>ULN, use \>4\*BL; blood urea nitrogen: \>2\*BL; creatinine: \>1.5\*BL.
Time frame: From Day 1 to Day 113, and including up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High alanine aminotransferase | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High bilirubin | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High aspartate aminotransferase | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High blood urea nitrogen | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High G-Glutamyl transferase | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High creatinine | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High alkaline phosphatase | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High creatinine | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High alkaline phosphatase | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High aspartate aminotransferase | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High alanine aminotransferase | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High G-Glutamyl transferase | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High bilirubin | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality | High blood urea nitrogen | 0 participants |
Secondary
Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality
BL=baseline; LLN=lower limit of normal; ULN=upper limit of normal. Marked abnormality criteria: Hemoglobin: \>3 g/dL decrease from BL. Hematocrit: \<0.75\*BL. Erythrocytes: \<0.75\*BL. Platelets: \<0.67\*LLN/\>1.5\*ULN, or if BL \<LLN, use 0.5\*BL/\<100,000 mm\^3. Leukocytes: \<0.75\*LLN/\>1.25\*ULN, or if BL\<LLN, use \<0.8\*BL/\>ULN, or if BL\>ULN, use \>1.2\*BL/\<LLN. Neutrophils+bands: \<1.0\*10\^3 c/uL. Eosinophils: \>0.750\*10\^3 c/uL. Basophils: \> 400 mm\^3. Monocytes: \>2000 mm\^3. Lymphocytes: \<0.750\*10\^3 c/uL/\>7.50\*10\^3 c/uL.
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low erythrocytes | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low neutrophils+bands | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High platelets | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low lymphocytes | 2 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low hematocrit | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High lymphocytes | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low leukocytes | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High monocytes | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low platelets | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High basophils | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High leukocytes | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High eosinophils | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low hemoglobin | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High eosinophils | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low hemoglobin | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low hematocrit | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low erythrocytes | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low platelets | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High platelets | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low leukocytes | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High leukocytes | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low neutrophils+bands | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | Low lymphocytes | 2 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High lymphocytes | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High monocytes | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality | High basophils | 0 participants |
Secondary
Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality
LLN=lower limit of normal; ULN=upper limit of normal; BL-baseline. Marked abnormality c: serum glucose:\<65 mg/dL/\>220 mg/dL; fasting serum glucose: \<0.8\* LLN/\>1.5\* ULN, or if BL\<LLN, use 0.8\*BL or \>ULN, or if BL\>ULN, use \>2.0\*BL or \<LLN; total protein: \<0.9\*LLN/\>1.1\* ULN; albumin: \<0.9\*LLN,or if BL\<LLN, use \<0.75 BL; uric acid: \>1.5\* ULN, or if BL\>ULN, use \>2\*BL. Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, red blood cells, white blood cells):Use ≥2 when BL value missing or value ≥4,or when predose=0 or 0.5. Use ≥3 when predose=1. Use ≥4 when predose=2 or 3
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low serum glucose (n=27, n=23) | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High serum glucose (n=27, n=23) | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low fasting glucose (n=20, n=17) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High fasting glucose (n=20, n=17) | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low total protein (n=27, n=23) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High total protein (n=27, n=23) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low albumin (n=27, n=23) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High uric acid (n=27, n=23) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine protein (n=27, n=23) | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine glucose (n=27, n=23) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine blood (n=27, n=23) | 2 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High leukocyte esterase (n=27, n=23) | 4 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine white blood cells (n=10, n=9) | 2 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine red blood cells (n=10, n=8) | 3 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine blood (n=27, n=23) | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low serum glucose (n=27, n=23) | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High uric acid (n=27, n=23) | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High serum glucose (n=27, n=23) | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine white blood cells (n=10, n=9) | 3 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low fasting glucose (n=20, n=17) | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine protein (n=27, n=23) | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High fasting glucose (n=20, n=17) | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High leukocyte esterase (n=27, n=23) | 4 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low total protein (n=27, n=23) | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine glucose (n=27, n=23) | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High total protein (n=27, n=23) | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | High urine red blood cells (n=10, n=8) | 3 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality | Low albumin (n=27, n=23) | 0 participants |
Secondary
Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis
Bone erosion and osteitis were assessed at a total of 23 anatomic locations according to erosion (for bone erosion) or involvement (for osteitis) of the original articular bone. Synovitis assessed as above-normal post-gadolinium enhancement in 3 wrist regions: distal radioulnar joint, radiocarpal joint, and intercarpal and carpometacarpal joints.
Time frame: Baseline to Day 113
Population: All randomized participants who received at least 1 dose of study medication and had erosion, edema, and synovitis assessments available at baseline and Day 113.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | 0 newly involved joints (Bone Erosion) | 20 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | ≥1 newly involved joints (Bone Erosion) | 5 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | 0 newly involved joints (Edema/Osteitis) | 18 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | ≥1 newly involved joints (Edema/Osteitis) | 7 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | 0 newly involved joints (Synovitis) | 23 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | ≥1 newly involved joints (Synovitis) | 2 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | 0 newly involved joints (Synovitis) | 20 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | 0 newly involved joints (Bone Erosion) | 16 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | ≥1 newly involved joints (Edema/Osteitis) | 7 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | ≥1 newly involved joints (Bone Erosion) | 7 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | ≥1 newly involved joints (Synovitis) | 3 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis | 0 newly involved joints (Edema/Osteitis) | 16 participants |
Secondary
Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest
Peri-infusional AEs are AEs occurring during the first 24 hours after the start of study drug infusion. An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. AEs considered possibly, probably, or certainly related to study treatment were graded according to Common Terminology Criteria for Adverse Events, Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).
Time frame: From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 nausea | 3 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 headache | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 2 headache | 1 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 flushing | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 2 arthralgia | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 cough | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 2 arthralgia | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 nausea | 0 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 flushing | 2 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 headache | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 1 cough | 1 participants |
| Placebo + Methotrexate | Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest | Grade 2 headache | 1 participants |
Secondary
Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay
On-Rx=on treatment; post-Rx=post treatment. ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1.
Time frame: Day 1 to Day 113
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay | Overall on-Rx visits, CTLA4 + possibly Ig (n=27) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay | Overall on-Rx visits, Ig and/or junction (n=27) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay | Overall post-Rx visits, CTLA4 + possibly Ig (n=1) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay | Overall post-Rx visits, Ig and/or junction (n=1) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay | Overall visits, CTLA4 + possibly Ig (n=27) | 0 participants |
| Abatacept + Methotrexate | Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay | Overall visits, Ig and/or junction (n=27) | 0 participants |
Secondary
Double-blind Period:Number of Participants With Significantly Abnormal Changes in Vital Signs
Vital signs, which included blood pressure, heart rate, respiration, and temperature, were monitored predose and 1 hour after start of infusion. Changes in vital signs were determined to be significantly abnormal at the discretion of the investigator but were generally those that either exceeded, or failed to reach, normal parameters. Normal vital sign parameter ranges varied by site.
Time frame: Days 1, 15, 29, 57, 85, and 113
Population: All randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept + Methotrexate | Double-blind Period:Number of Participants With Significantly Abnormal Changes in Vital Signs | 0 participants |
| Placebo + Methotrexate | Double-blind Period:Number of Participants With Significantly Abnormal Changes in Vital Signs | 0 participants |