Trial Outcomes & Findings for A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) (ALABASTER) (NCT NCT01235507)
NCT ID: NCT01235507
Last Updated: 2014-11-07
Results Overview
AEs, SAEs and AESI were recorded from the Screening Visit until the final visit at Week 24.
COMPLETED
PHASE3
71 participants
Screening Visit, Baseline, Weeks 4, 8, 12, 16, 20 and 24
2014-11-07
Participant Flow
Participant milestones
| Measure |
Tocilizumab Plus Methotrexate (MTX)
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) (maximum 800 mg) intravenously (IV) every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg per week (mg/week) of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Overall Study
STARTED
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71
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Overall Study
COMPLETED
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69
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Overall Study
NOT COMPLETED
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2
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Reasons for withdrawal
| Measure |
Tocilizumab Plus Methotrexate (MTX)
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) (maximum 800 mg) intravenously (IV) every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg per week (mg/week) of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Overall Study
Adverse Event
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1
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Overall Study
Withdrawal by Subject
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1
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Baseline Characteristics
A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) (ALABASTER)
Baseline characteristics by cohort
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Age, Continuous
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49.76 years
STANDARD_DEVIATION 12.37 • n=39 Participants
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Sex: Female, Male
Female
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61 Participants
n=39 Participants
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Sex: Female, Male
Male
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10 Participants
n=39 Participants
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PRIMARY outcome
Timeframe: Screening Visit, Baseline, Weeks 4, 8, 12, 16, 20 and 24Population: Safety Analysis Population: All participants enrolled in the study who received at least 1 dose of study medication and had at least 1 post-baseline assessment of safety (such as laboratory data, vital signs, or AEs) were included.
AEs, SAEs and AESI were recorded from the Screening Visit until the final visit at Week 24.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)
AEs
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14.1 percentage of participants
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Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)
SAE
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2.8 percentage of participants
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Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)
AESI
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4.2 percentage of participants
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SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16 and 24Population: ITT Population; number (n) = number of participants analyzed for the given parameter at the specified time point
DAS28 was calculated using the 28 joints count, the C-reactive protein levels (CRP) and participant's global assessment (PtGA) of disease activity. The following formula was used to determine DAS28. DAS28 (equals) = 0.56 × (square root of) √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100- millimeter \[mm\] visual analog scale \[ VAS\]). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Baseline (n=71)
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6.28 units on a scale
Standard Deviation 1.06
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Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Week 8 (n=71)
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3.84 units on a scale
Standard Deviation 1.29
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Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Change from Baseline to Week 8 (n=71)
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-2.44 units on a scale
Standard Deviation 0.98
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Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Week 16 (n=71)
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3.19 units on a scale
Standard Deviation 1.23
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Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Change from Baseline to Week 16 (n=71)
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-3.09 units on a scale
Standard Deviation 1.01
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Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Week 24 (n=69)
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2.65 units on a scale
Standard Deviation 1.23
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Mean Disease Activity Score Based on 28 Joint Count (DAS28) by Visit
Change from Baseline to Week 24 (n=69)
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-3.62 units on a scale
Standard Deviation 1.22
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SECONDARY outcome
Timeframe: Weeks 8, 16 and 24Population: ITT Population; n= number of participants analyzed for the given parameter at the specified time point
DAS28 was calculated using the 28 joints count, the CRP and PtGA of disease activity. The following formula was used to determine DAS28. DAS28 = 0.56 × √(TJC28) + 0.28 × √(SJC28) + 0.36 × ln(CRP+1) + 0.014 × GH + 0.96 where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, CRP = C-reactive protein (mg/L), and GH = general health, determined by participant's global assessment of disease activity (100-mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Participants were considered to have low disease activity when DAS28 was less than or equal to (≤) 3.2 and in clinical remission when DAS28 scores were less than (\<) 2.6
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
Week 8 CR (n=71)
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14.1 percentage of participants
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Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
Week 8 LDA (n=71)
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31.0 percentage of participants
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Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
Week 16 CR (n=71)
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39.4 percentage of participants
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Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
Week 16 LDA (n=71)
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49.3 percentage of participants
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Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
Week 24 CR (n=69)
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47.8 percentage of participants
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Percentage of Participants Achieving Low Disease Activity (LDA) and Clinical Remission (CR) as Assessed Using DAS28
Week 24 LDA (n=69)
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71.0 percentage of participants
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SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16 and 24Population: ITT Population; n= number of participants analyzed for the given parameter at the specified time point
66 and 68 joints were assessed by the physician for tenderness or swelling respectively. The joints were counted as tender/not tender (tender=1; not tender=0) and swollen/not swollen (swollen=1; not swollen=0) and scored. The scores ranged from 0 to 66 for TJC and 0 to 68 for SJC. A negative change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Swollen and Tender Joint Counts
Baseline SJC (n=71)
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19.48 Joints
Standard Deviation 10.97
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Swollen and Tender Joint Counts
Week 8 SJC (n=71)
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6.72 Joints
Standard Deviation 5.76
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Swollen and Tender Joint Counts
Change in SJC from Baseline to Week 8 (n=71)
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-12.76 Joints
Standard Deviation 10.93
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Swollen and Tender Joint Counts
Week 16 SJC (n=71)
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3.73 Joints
Standard Deviation 4.88
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Swollen and Tender Joint Counts
Change in SJC from Baseline to Week 16 (n=71)
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-15.75 Joints
Standard Deviation 9.59
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Swollen and Tender Joint Counts
Week 24 SJC (n=69)
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2.43 Joints
Standard Deviation 4.12
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Swollen and Tender Joint Counts
Change in SJC from Baseline to Week 24 (n=69)
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-16.83 Joints
Standard Deviation 9.51
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Swollen and Tender Joint Counts
Baseline TJC (n=71)
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24.62 Joints
Standard Deviation 11.84
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Swollen and Tender Joint Counts
Week 8 TJC (n=71)
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10.59 Joints
Standard Deviation 8.38
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Swollen and Tender Joint Counts
Change in TJC from Baseline to Week 8 (n=71)
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-14.03 Joints
Standard Deviation 12.21
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Swollen and Tender Joint Counts
Week 16 TJC (n=71)
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7.12 Joints
Standard Deviation 7.25
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Swollen and Tender Joint Counts
Change in TJC from Baseline to Week 16 (n=71)
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-17.49 Joints
Standard Deviation 11.02
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Swollen and Tender Joint Counts
Week 24 TJC (n=69)
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5.03 Joints
Standard Deviation 5.97
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Swollen and Tender Joint Counts
Change in TJC from Baseline to Week 24 (n=69)
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-19.48 Joints
Standard Deviation 10.27
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SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16 and 24Population: ITT Population; n=number of participants analyzed for the given parameter at the specified time point
Physician's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Physician's Global Assessment of Disease Activity
Baseline (n=71)
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67.44 mm
Standard Deviation 17.72
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Physician's Global Assessment of Disease Activity
Week 8 (n=71)
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35.99 mm
Standard Deviation 20.53
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Physician's Global Assessment of Disease Activity
Change from Baseline to Week 8 (n=71)
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-31.45 mm
Standard Deviation 17.76
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Physician's Global Assessment of Disease Activity
Week 16 (n=71)
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26.48 mm
Standard Deviation 20.48
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Physician's Global Assessment of Disease Activity
Change from Baseline to Week 16 (n=71)
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-40.97 mm
Standard Deviation 20.7
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Physician's Global Assessment of Disease Activity
Week 24 (n=69)
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19.28 mm
Standard Deviation 17.48
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Physician's Global Assessment of Disease Activity
Change from Baseline to Week 24 (n=69)
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-48.09 mm
Standard Deviation 19.69
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SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16 and 24Population: ITT Population; n=number of participants analyzed for the given parameter at the specified time point
Participant's global assessment of disease activity was performed using a 100 mm VAS ranging from no arthritis activity (0) to maximal arthritis activity (100). The distance in mm from the left edge of the scale was measured. Higher scores indicated higher disease activity. A negative change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Participant's Global Assessment of Disease Activity
Baseline (n=71)
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70 mm
Standard Deviation 16.84
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Participant's Global Assessment of Disease Activity
Week 8 (n=71)
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42.87 mm
Standard Deviation 20.67
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Participant's Global Assessment of Disease Activity
Change from Baseline to Week 8 (n=71)
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-27.13 mm
Standard Deviation 21.60
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Participant's Global Assessment of Disease Activity
Week 16 (n=71)
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33.20 mm
Standard Deviation 21.16
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Participant's Global Assessment of Disease Activity
Change from Baseline to Week 16 (n=71)
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-36.80 mm
Standard Deviation 22.43
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Participant's Global Assessment of Disease Activity
Week 24 (n=69)
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24.56 mm
Standard Deviation 20.15
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Participant's Global Assessment of Disease Activity
Change from Baseline to Week 24 (n=69)
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-45.30 mm
Standard Deviation 22.74
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SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16 and 24Population: ITT Population; n=number of participants analyzed for the given parameter at the specified time point
Participant's global assessment of pain was performed using a 100 mm VAS ranging from no pain (0) at the left edge to unbearable pain (100) at the right edge. The distance in mm from the left edge of the scale was measured. A negative change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Participant's Global Assessment of Pain
Baseline (n=71)
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69.73 mm
Standard Deviation 17.60
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Participant's Global Assessment of Pain
Week 8 (n=71)
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42.34 mm
Standard Deviation 19.25
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Participant's Global Assessment of Pain
Change from Baseline to Week 8 (n=71)
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-27.39 mm
Standard Deviation 19.44
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Participant's Global Assessment of Pain
Week 16 (n=71)
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33.94 mm
Standard Deviation 21.05
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Participant's Global Assessment of Pain
Change from Baseline to Week 16 (n=71)
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-35.79 mm
Standard Deviation 21.52
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Participant's Global Assessment of Pain
Week 24 (n=69)
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25.54 mm
Standard Deviation 21.37
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Participant's Global Assessment of Pain
Change from Baseline to Week 24 (n=69)
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-44.04 mm
Standard Deviation 25.11
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SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16 and 24Population: ITT Population; n=number of participants analyzed for the given parameter at the specified time point
CRP is a marker of acute phase inflammation and is measured in mg/L. A negative change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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CRP Levels
Baseline (n=62)
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11.98 mg/L
Standard Deviation 15.04
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CRP Levels
Week 8 (n=65)
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5.11 mg/L
Standard Deviation 14.12
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CRP Levels
Change from Baseline to Week 8 (n=61)
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-6.68 mg/L
Standard Deviation 17.88
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CRP Levels
Week 16 (n=67)
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3.84 mg/L
Standard Deviation 11.91
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CRP Levels
Change from Baseline to Week 16 (n=60)
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-8.0 mg/L
Standard Deviation 18.39
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CRP Levels
Week 24 (n=68)
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5.53 mg/L
Standard Deviation 14.07
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CRP Levels
Change from Baseline to Week 24 (n=60)
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-5.97 mg/L
Standard Deviation 21.12
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SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16 and 24Population: ITT Population; n=number of participants analyzed for the given parameter at the specified time point
ESR is a marker of inflammation and is measured in millimeters per hour (mm/hour). A negative change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab Plus MTX
n=71 Participants
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Erythrocyte Sedimentation Rate (ESR)
Baseline (n=71)
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36.13 mm/hour
Standard Deviation 24.82
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Erythrocyte Sedimentation Rate (ESR)
Week 8 (n=71)
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9.04 mm/hour
Standard Deviation 8.83
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Erythrocyte Sedimentation Rate (ESR)
Change from Baseline to Week 8 (n=71
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-27.09 mm/hour
Standard Deviation 22.98
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Erythrocyte Sedimentation Rate (ESR)
Week 16 (n=71)
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8.71 mm/hour
Standard Deviation 6.39
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Erythrocyte Sedimentation Rate (ESR)
Change from Baseline to Week 16 (n=71)
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-27.42 mm/hour
Standard Deviation 23.07
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Erythrocyte Sedimentation Rate (ESR)
Week 24 (n=69)
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10.3 mm/hour
Standard Deviation 12.81
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Erythrocyte Sedimentation Rate (ESR)
Change from Baseline to Week 24 (n=69)
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-25.72 mm/hour
Standard Deviation 27.54
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Adverse Events
Tocilizumab Plus MTX
Serious adverse events
| Measure |
Tocilizumab Plus MTX
n=71 participants at risk
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm - Skin
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1.4%
1/71 • Adverse events were recorded from the date of screening until the final visit at Week 24
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Immune system disorders
Exacerbation of RA
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1.4%
1/71 • Adverse events were recorded from the date of screening until the final visit at Week 24
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Other adverse events
| Measure |
Tocilizumab Plus MTX
n=71 participants at risk
Participants received tocilizumab 8 mg/kg (maximum 800 mg) IV every 4 weeks for a total of 6 infusions along with methotrexate stable dose as prescribed. Participants also received a stable dose of at least 5 mg/week of folate (or equivalent) given as either a single dose or divided into daily doses to achieve at least 5 mg/week, per investigator discretion.
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|---|---|
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Blood and lymphatic system disorders
Leukocytopenia
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4.2%
3/71 • Adverse events were recorded from the date of screening until the final visit at Week 24
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Hepatobiliary disorders
Elevated AST
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2.8%
2/71 • Adverse events were recorded from the date of screening until the final visit at Week 24
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Blood and lymphatic system disorders
Thrombocytopenia
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2.8%
2/71 • Adverse events were recorded from the date of screening until the final visit at Week 24
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER