Trial Outcomes & Findings for An Open-label Study With Tocilizumab in Patients With Rheumatoid Arthritis in a Local Environment (NCT NCT01254331)
NCT ID: NCT01254331
Last Updated: 2015-02-26
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
51 participants
Primary outcome timeframe
Baseline, every 4 weeks through Week 52
Results posted on
2015-02-26
Participant Flow
Participant milestones
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the European League Against Rheumatism (EULAR) category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Initial Phase
STARTED
|
51
|
|
Initial Phase
COMPLETED
|
46
|
|
Initial Phase
NOT COMPLETED
|
5
|
|
Extension Phase
STARTED
|
45
|
|
Extension Phase
COMPLETED
|
41
|
|
Extension Phase
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the European League Against Rheumatism (EULAR) category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Initial Phase
Adverse Event
|
3
|
|
Initial Phase
Withdrawal by Subject
|
1
|
|
Initial Phase
Pregnancy
|
1
|
|
Extension Phase
Lack of Efficacy
|
1
|
|
Extension Phase
Lost to Follow-up
|
3
|
Baseline Characteristics
An Open-label Study With Tocilizumab in Patients With Rheumatoid Arthritis in a Local Environment
Baseline characteristics by cohort
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Age, Continuous
|
48.01 years
STANDARD_DEVIATION 10.72 • n=5 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, every 4 weeks through Week 52Population: Safety population
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death
AEs
|
78.4 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death
SAEs
|
5.9 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death
Related AEs
|
15.2 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death
Discontinuation due to AE
|
7.8 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death
Death
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; number (n)= number of participants analyzed at a specific visit
DAS28 calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and participant's global assessment (PtGA) of disease activity by Visual analog Scale (VAS; participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤) 3.2 equals (=) low disease activity (LDA), DAS28 greater than (\>) 3.2 to 5.1 = moderate to high disease activity. A reduction of at least 1.2 units in DAS28 was considered clinically significant improvement.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
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|---|---|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 4 (n=51)
|
56.9 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 8 (n=49)
|
81.6 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 12 (n=47)
|
83.0 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 16 (n=47)
|
80.9 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 20 (n=46)
|
95.7 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 24 (n=46)
|
91.3 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 36 (n=43)
|
86.0 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 48 (n=41)
|
92.7 percentage of participants
|
|
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
Week 52 (n=42)
|
90.5 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants analyzed at a specific visit
DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than (\<) 3.2 = LDA.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
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|---|---|
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Percentage of Participants Achieving LDA Assessed Using DAS28
Week 4 (n=51)
|
9.8 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 8 (n=49)
|
26.5 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 12 (n=47)
|
34.0 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 16 (n=47)
|
36.2 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 20 (n=46)
|
52.2 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 24 (n=46)
|
47.8 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 36 (n=43)
|
55.8 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 48 (n=41)
|
65.9 percentage of participants
|
|
Percentage of Participants Achieving LDA Assessed Using DAS28
Week 52 (n=42)
|
61.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants analyzed at a specific visit
DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Participants were considered in remission when reaching a DAS28 score \<2.6.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
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|---|---|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Baseline (n=51)
|
0.0 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 4 (n=51)
|
2.0 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 8 (n=49)
|
12.2 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 12 (n=47)
|
23.4 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 16 (n=47)
|
23.4 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 20 (n=46)
|
32.6 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 24 (n=46)
|
41.3 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 36 (n=43)
|
44.2 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 52 (n=42)
|
45.2 percentage of participants
|
|
Percentage of Participants Achieving Remission Assessed Using DAS28
Week 48 (n=41)
|
41.5 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population
The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) C-reactive protein (CRP) at each visit.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
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|---|---|
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Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 4 ACR20
|
29.2 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 4 ACR50
|
6.3 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 4 ACR70
|
0.0 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 8 ACR20
|
54.3 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 8 ACR50
|
21.7 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 8 ACR70
|
4.3 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 12 ACR20
|
61.2 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 12 ACR50
|
32.7 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 12 ACR70
|
12.2 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 16 ACR20
|
49.0 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 16 ACR50
|
24.5 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 16 ACR70
|
18.4 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 20 ACR20
|
70.8 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 20 ACR50
|
35.4 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 20 ACR70
|
12.5 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 24 ACR20
|
66.7 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 24 ACR50
|
33.3 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 24 ACR70
|
13.7 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 36 ACR20
|
54.2 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 36 ACR50
|
33.3 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 36 ACR70
|
14.6 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 48 ACR20
|
66.0 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 48 ACR50
|
48.9 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 48 ACR70
|
27.7 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 52 ACR20
|
58.3 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 52 ACR50
|
37.5 percentage of participants
|
|
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
Week 52 ACR70
|
18.8 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population
The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via (HAQ, and 5) CRP at each visit. The median time to achieve ACR20/ACR50/ACR70 was calculated using Kaplan-Meier estimates.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Time To Achieve ACR20/ACR50/ACR70
ACR20
|
8.0 weeks
Interval 4.0 to 20.0
|
|
Time To Achieve ACR20/ACR50/ACR70
ACR50
|
20.0 weeks
Interval 12.0 to
Calculation was not possible due to the small number of participants achieving ACR50
|
|
Time To Achieve ACR20/ACR50/ACR70
ACR70
|
NA weeks
Interval 20.0 to
Calculation was not possible due to the small number of participants achieving ACR70
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
28 joints were assessed for swelling and tenderness. Joints were classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) giving a total possible SJC and TJC score of 0 to 28 each.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
SJC and TJC
Baseline TJC (n=51)
|
14.3 joints
Interval 12.3 to 16.4
|
|
SJC and TJC
Baseline SJC (n=51)
|
7.0 joints
Interval 5.7 to 8.2
|
|
SJC and TJC
Week 4 TJC (n=51)
|
10.3 joints
Interval 8.1 to 12.4
|
|
SJC and TJC
Week 4 SJC (n=51)
|
5.2 joints
Interval 3.9 to 6.5
|
|
SJC and TJC
Week 8 TJC (n=46)
|
5.0 joints
Interval 3.8 to 6.3
|
|
SJC and TJC
Week 8 SJC (n=49)
|
3.4 joints
Interval 2.5 to 4.3
|
|
SJC and TJC
Week 12 TJC (n=47)
|
5.1 joints
Interval 3.6 to 6.6
|
|
SJC and TJC
Week 12 SJC (n=47)
|
2.6 joints
Interval 1.7 to 3.4
|
|
SJC and TJC
Week 16 TJC (n=47)
|
4.7 joints
Interval 3.1 to 6.2
|
|
SJC and TJC
Week 16 SJC (n=47)
|
3.1 joints
Interval 1.9 to 4.4
|
|
SJC and TJC
Week 20 TJC (n=46)
|
3.4 joints
Interval 2.4 to 4.3
|
|
SJC and TJC
Week 20 SJC (n=46)
|
1.6 joints
Interval 1.1 to 2.2
|
|
SJC and TJC
Week 24 TJC (n=46)
|
3.5 joints
Interval 2.2 to 4.9
|
|
SJC and TJC
Week 24 SJC (n=46)
|
1.6 joints
Interval 0.8 to 2.4
|
|
SJC and TJC
Week 28 TJC (n=34)
|
3.3 joints
Interval 2.3 to 4.3
|
|
SJC and TJC
Week 28 SJC (n=34)
|
1.3 joints
Interval 0.7 to 2.0
|
|
SJC and TJC
Week 32 TJC (n=34)
|
2.5 joints
Interval 1.8 to 3.3
|
|
SJC and TJC
Week 32 SJC (n=34)
|
1.4 joints
Interval 0.7 to 2.1
|
|
SJC and TJC
Week 36 TJC (n=41)
|
3.6 joints
Interval 2.1 to 5.0
|
|
SJC and TJC
Week 36 SJC (n=41)
|
2.0 joints
Interval 1.2 to 2.8
|
|
SJC and TJC
Week 40 TJC (n=33)
|
2.6 joints
Interval 1.7 to 3.6
|
|
SJC and TJC
Week 40 SJC (n=33)
|
1.3 joints
Interval 0.5 to 2.0
|
|
SJC and TJC
Week 44 TJC (n=34)
|
2.6 joints
Interval 1.4 to 3.8
|
|
SJC and TJC
Week 48 TJC (n=39)
|
2.4 joints
Interval 1.4 to 3.4
|
|
SJC and TJC
Week 48 SJC (n=39)
|
1.2 joints
Interval 0.7 to 1.7
|
|
SJC and TJC
Week 52 TJC (n=40)
|
2.8 joints
Interval 1.4 to 4.2
|
|
SJC and TJC
Week 52 SJC (n=40)
|
1.9 joints
Interval 1.2 to 2.7
|
|
SJC and TJC
Week 44 SJC (n=34)
|
1.5 joints
Interval 0.7 to 2.4
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
The participants assessed their pain using a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". The participants marked the line corresponding to their level of pain and the distance from the left edge was measured.
Outcome measures
| Measure |
Tocilizumab
n=50 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Baseline (n=50)
|
67.6 mm
Interval 62.5 to 72.6
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 4 (n=48)
|
49.4 mm
Interval 43.8 to 55.0
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 8 (n=47)
|
40.6 mm
Interval 35.3 to 46.0
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 12 (n=47)
|
36.0 mm
Interval 30.5 to 41.5
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 16 (n=48)
|
36.1 mm
Interval 30.8 to 41.4
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 20 (n=45)
|
33.2 mm
Interval 27.8 to 38.5
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 24 (n=46)
|
28.5 mm
Interval 23.6 to 33.3
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 36 (n=44)
|
30.0 mm
Interval 23.1 to 36.9
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 48 (n=41)
|
22.9 mm
Interval 15.9 to 29.9
|
|
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
Week 52 (n=40)
|
23.7 mm
Interval 17.4 to 30.0
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
The participant's global assessment of disease activity was assessed using a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). The participants marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Assessment of Global Disease by the Participant Using VAS
Baseline (n=51)
|
64.7 mm
Interval 59.6 to 69.7
|
|
Assessment of Global Disease by the Participant Using VAS
Week 4 (n=51)
|
52.9 mm
Interval 46.0 to 59.9
|
|
Assessment of Global Disease by the Participant Using VAS
Week 8 (n=48)
|
40.9 mm
Interval 36.2 to 45.6
|
|
Assessment of Global Disease by the Participant Using VAS
Week 12 (n=47)
|
37.1 mm
Interval 32.0 to 42.2
|
|
Assessment of Global Disease by the Participant Using VAS
Week 16 (n=48)
|
34.4 mm
Interval 28.7 to 40.0
|
|
Assessment of Global Disease by the Participant Using VAS
Week 20 (n=45)
|
32.6 mm
Interval 27.2 to 38.0
|
|
Assessment of Global Disease by the Participant Using VAS
Week 24 (n=46)
|
29.3 mm
Interval 24.3 to 34.4
|
|
Assessment of Global Disease by the Participant Using VAS
Week 36 (n=44)
|
28.7 mm
Interval 21.8 to 35.6
|
|
Assessment of Global Disease by the Participant Using VAS
Week 48 (n=41)
|
20.1 mm
Interval 14.6 to 25.5
|
|
Assessment of Global Disease by the Participant Using VAS
Week 52 (n=41)
|
24.1 mm
Interval 17.9 to 30.4
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). The physician marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Baseline (n=51)
|
58.8 mm
Interval 54.0 to 63.6
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 4 (n=51)
|
45.9 mm
Interval 41.1 to 50.7
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 8 (n=48)
|
35.5 mm
Interval 31.6 to 39.4
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 12 (n=47)
|
31.1 mm
Interval 26.7 to 35.5
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 16 (n=48)
|
32.3 mm
Interval 26.9 to 37.8
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 20 (n=45)
|
28.9 mm
Interval 24.0 to 33.9
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 24 (n=46)
|
26.4 mm
Interval 21.6 to 31.3
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 36 (n=44)
|
23.5 mm
Interval 17.8 to 29.2
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 48 (n=41)
|
19.6 mm
Interval 14.8 to 24.5
|
|
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
Week 52 (n=40)
|
19.6 mm
Interval 14.8 to 24.4
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
Physical function was assessed using the HAQ. The HAQ scores range from 0 to 3 with, 0: no assistance needed, 1: participant uses a special device for day-to-day activities, 2: participant usually needs help from another person, and 3: participant uses BOTH a special device AND another person's help for day-to-day activities.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Baseline (n=51)
|
1.7 units on a scale
Interval 1.5 to 1.9
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 4 (n=50)
|
1.2 units on a scale
Interval 1.0 to 1.4
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 8 (n=48)
|
1.7 units on a scale
Interval 0.6 to 2.7
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 12 (n=47)
|
0.9 units on a scale
Interval 0.7 to 1.1
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 16 (n=48)
|
0.8 units on a scale
Interval 0.6 to 1.0
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 20 (n=46)
|
0.8 units on a scale
Interval 0.6 to 1.0
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 24 (n=46)
|
0.7 units on a scale
Interval 0.6 to 0.9
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 36 (n=40)
|
1.0 units on a scale
Interval 0.6 to 1.4
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 48 (n=37)
|
0.9 units on a scale
Interval 0.6 to 1.1
|
|
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Week 52 (n=38)
|
0.8 units on a scale
Interval 0.6 to 1.0
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
CRP is an acute phase reactant and levels of CRP increase with inflammation. CRP is measured as milligrams per liter (mg/L).
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Mean C-Reactive Protein (CRP) Levels
Baseline (n=51)
|
26.6 mg/L
Interval 18.4 to 34.8
|
|
Mean C-Reactive Protein (CRP) Levels
Week 4 (n=51)
|
10.4 mg/L
Interval 4.9 to 15.9
|
|
Mean C-Reactive Protein (CRP) Levels
Week 8 (n=49)
|
9.5 mg/L
Interval 4.3 to 14.6
|
|
Mean C-Reactive Protein (CRP) Levels
Week 12 (n=47)
|
8.4 mg/L
Interval 4.7 to 12.1
|
|
Mean C-Reactive Protein (CRP) Levels
Week 16 (n=46)
|
9.1 mg/L
Interval 4.7 to 13.5
|
|
Mean C-Reactive Protein (CRP) Levels
Week 20 (n=46)
|
10.9 mg/L
Interval 5.9 to 15.9
|
|
Mean C-Reactive Protein (CRP) Levels
Week 24 (n=44)
|
11.0 mg/L
Interval 5.1 to 16.8
|
|
Mean C-Reactive Protein (CRP) Levels
Week 36 (n=43)
|
12.4 mg/L
Interval 2.1 to 22.7
|
|
Mean C-Reactive Protein (CRP) Levels
Week 48 (n=42)
|
10.4 mg/L
Interval 4.3 to 16.4
|
|
Mean C-Reactive Protein (CRP) Levels
Week 52 (n=40)
|
7.4 mg/L
Interval 4.3 to 10.5
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
ESR is an acute phase reactant and levels of ESR increase with inflammation. ESR is measured as mm/hour.
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Baseline (n=51)
|
44.1 mm/hour
Interval 35.7 to 52.4
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 4 (n=51)
|
21.0 mm/hour
Interval 13.2 to 28.9
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 8 (n=49)
|
22.1 mm/hour
Interval 12.8 to 31.4
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 12 (n=47)
|
17.0 mm/hour
Interval 12.4 to 21.7
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 16 (n=47)
|
16.8 mm/hour
Interval 11.5 to 22.0
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 20 (n=46)
|
13.5 mm/hour
Interval 9.2 to 17.8
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 24 (n=46)
|
18.4 mm/hour
Interval 12.3 to 24.5
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 36 (n=43)
|
15.6 mm/hour
Interval 9.2 to 22.0
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 48 (n=42)
|
17.7 mm/hour
Interval 11.8 to 23.6
|
|
Mean Erythrocyte Sedimentation Rate (ESR) Levels
Week 52 (n=42)
|
16.9 mm/hour
Interval 11.2 to 22.6
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, and 24Population: Safety population; n=number of participants analyzed for the given parameter at the specified visit
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Percentage of Participants Experiencing Fatigue
Baseline (n=50)
|
22.0 percentage of participants
|
|
Percentage of Participants Experiencing Fatigue
Week 4 (n=49)
|
16.3 percentage of participants
|
|
Percentage of Participants Experiencing Fatigue
Week 8 (n=48)
|
4.2 percentage of participants
|
|
Percentage of Participants Experiencing Fatigue
Week 12 (n=45)
|
13.3 percentage of participants
|
|
Percentage of Participants Experiencing Fatigue
Week 16 (n=47)
|
10.6 percentage of participants
|
|
Percentage of Participants Experiencing Fatigue
Week 20 (n=44)
|
11.4 percentage of participants
|
|
Percentage of Participants Experiencing Fatigue
Week 24 (n=46)
|
10.9 percentage of participants
|
SECONDARY outcome
Timeframe: Week 52Population: Safety population
Outcome measures
| Measure |
Tocilizumab
n=51 Participants
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Number of Participants Who Discontinued Tocilizumab
|
1 participants
|
Adverse Events
Tocilizumab
Serious events: 3 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tocilizumab
n=51 participants at risk
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Nervous system disorders
Confusional syndrome
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Surgical and medical procedures
Whitlows of the toe
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural-pneumopathy
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
Other adverse events
| Measure |
Tocilizumab
n=51 participants at risk
Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks.
|
|---|---|
|
Infections and infestations
Oral ulcer
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Surgical and medical procedures
Acute appendicitis
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Musculoskeletal and connective tissue disorders
Osteoarticular fracture (fifth metatarsal)
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Musculoskeletal and connective tissue disorders
Osteomalacia
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous lesions
|
15.7%
8/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
3.9%
2/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
General disorders
Flu syndrome
|
5.9%
3/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Renal and urinary disorders
Urinary infection
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Investigations
Increased ALT/AST
|
29.4%
15/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Investigations
Hypercholesterolemia
|
35.3%
18/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Investigations
Hypertriglyceridemia
|
33.3%
17/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Investigations
Neutropenia
|
15.7%
8/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Investigations
Cytolysis
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Investigations
Reticulocytosis
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Infections and infestations
Oral thrush
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
General disorders
Headache
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Ear and labyrinth disorders
Dizziness
|
3.9%
2/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
General disorders
Asthenia
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Skin and subcutaneous tissue disorders
Erythematous plaque of Elbows
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Gastrointestinal disorders
Hiatal hernia esopahgitis
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Skin and subcutaneous tissue disorders
Erythematous purpuric lesions
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Skin and subcutaneous tissue disorders
Papular skin lesions
|
5.9%
3/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Hepatobiliary disorders
Hyperbilirubinemai
|
3.9%
2/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Gastrointestinal disorders
Lower gastrointestinal bleeding - Hemorrhoids
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
General disorders
Vasodilation of feet
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Blood and lymphatic system disorders
Hyperisonophilia
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
General disorders
Hypokalemia
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
General disorders
Hallux Abscess
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Infections and infestations
Bronchial Infectious syndrome
|
3.9%
2/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
|
Gastrointestinal disorders
Epigastric pain
|
2.0%
1/51 • AEs were recorded from the date of first infusion until the end of study at 52 weeks.
|
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