Trial Outcomes & Findings for A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic and/or Biologic DMARDS (NCT NCT01149057)
NCT ID: NCT01149057
Last Updated: 2016-11-02
Results Overview
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
COMPLETED
PHASE4
145 participants
Baseline, Week 24
2016-11-02
Participant Flow
Participant milestones
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilograms (mg/kg) intravenous (IV) infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Overall Study
STARTED
|
145
|
|
Overall Study
COMPLETED
|
88
|
|
Overall Study
NOT COMPLETED
|
57
|
Reasons for withdrawal
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilograms (mg/kg) intravenous (IV) infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Overall Study
Lack of Efficacy
|
16
|
|
Overall Study
Adverse Event
|
13
|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Positive Hepatitis B Core Antibody
|
5
|
|
Overall Study
B Cell Depletion
|
4
|
|
Overall Study
Participant Non-Compliance
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
High Parathyroid Hormone Value
|
1
|
|
Overall Study
Other
|
6
|
Baseline Characteristics
A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic and/or Biologic DMARDS
Baseline characteristics by cohort
| Measure |
Tocilizumab
n=145 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Age, Continuous
|
53.4 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
|
Gender
Female
|
121 Participants
n=5 Participants
|
|
Gender
Male
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: ITT population. Number of participants analysed=participants with available data for this endpoint. Here, 'n' signifies participants with available data at specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=142 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 24 in Intent-to-treat (ITT) Population
Baseline (n=142)
|
21.2 units on a scale
Standard Deviation 11.8
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 24 in Intent-to-treat (ITT) Population
Change From Baseline at Week 24 (n=118)
|
5.4 units on a scale
Standard Deviation 9.6
|
PRIMARY outcome
Timeframe: Baseline, Week 48Population: ITT population. Number of participants analyzed=participants with available data at specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=97 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in FACIT Fatigue Score at Week 48 in ITT Population
|
6.7 units on a scale
Standard Deviation 10.5
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: ITT population. Number of participants analyzed=participants with available data at specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=75 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in FACIT Fatigue Score at Week 72 in ITT Population
|
7.1 units on a scale
Standard Deviation 10.7
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: ITT population. Number of participants analyzed=participants with available data at specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=83 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in FACIT Fatigue Score at Week 96 in ITT Population
|
7.3 units on a scale
Standard Deviation 10.4
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: Per Protocol (PP) population: all participants who completed the study. Number of participants analyzed=participants with available data for this outcome. Here 'n' signifies the participants with available data for specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=86 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in FACIT Fatigue Score at Week 24 in Per Protocol (PP) Population
Baseline (n=86)
|
20.9 units on a scale
Standard Deviation 10.9
|
|
Change From Baseline in FACIT Fatigue Score at Week 24 in Per Protocol (PP) Population
Change From Baseline at Week 24 (n=80)
|
5.0 units on a scale
Standard Deviation 9.7
|
PRIMARY outcome
Timeframe: Baseline, Week 48Population: Per Protocol (PP) population. Number of participants analyzed=participants with available data for specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=81 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in FACIT Fatigue Score at Week 48 in PP Population
|
6.8 units on a scale
Standard Deviation 10.5
|
PRIMARY outcome
Timeframe: Baseline, Week 72Population: Per Protocol (PP) population. Number of participants analyzed=participants with available data for specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=71 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in FACIT Fatigue Score at Week 72 in PP Population
|
7.3 units on a scale
Standard Deviation 10.9
|
PRIMARY outcome
Timeframe: Baseline, Week 96Population: Per Protocol (PP) population. Number of participants analyzed=participants with available data for specified time point.
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Outcome measures
| Measure |
Tocilizumab
n=83 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in FACIT Fatigue Score at Week 96 in PP Population
|
7.3 units on a scale
Standard Deviation 10.4
|
SECONDARY outcome
Timeframe: Baseline, End of the study (up to Week 100)Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number of participants with available data for specified category.
BMD was measured by dual energy X-ray absorptiometry (DXA) and T-scores (a standard deviation \[SD\] compared with the peak BMD value of an adult aged from 20 to 30 years) were calculated. Osteopenia was defined by a T-score between -1 and -2.5 SD and osteoporosis as a T-score below -2.5 SD, according to the World Health Organization (WHO) guidelines. T-scores for L1-L4 lumbar spine, total spine, total hip (left), and femoral neck (left) were calculated.
Outcome measures
| Measure |
Tocilizumab
n=137 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
L1-L4: Baseline (n=40)
|
-0.81 T-score
Standard Deviation 1.35
|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
L1-L4: Change From Baseline at End (n=22)
|
-0.05 T-score
Standard Deviation 0.39
|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
Total Spine: Baseline (n=109)
|
-1.13 T-score
Standard Deviation 1.33
|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
Total Spine: Change From Baseline at End (n=65)
|
0.04 T-score
Standard Deviation 0.50
|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
Total Hip-Left: Baseline (n=124)
|
-0.67 T-score
Standard Deviation 1.16
|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
Total Hip-Left: Change From Baseline at End (n=76)
|
0.10 T-score
Standard Deviation 0.37
|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
Neck-Left: Baseline (n=137)
|
-1.11 T-score
Standard Deviation 1.17
|
|
Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study
Neck-Left: Change From Baseline at End (n=85)
|
-0.05 T-score
Standard Deviation 0.36
|
SECONDARY outcome
Timeframe: Weeks 24, 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number participants with available data for specified category.
Remission was defined as DAS28 score less than (\<) 2.6. The DAS28 score was a measure of the participant's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity (visual analog scale \[VAS\]: 0=no disease activity to 100=maximum disease activity) and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. In case of missing ESR value, C-Reactive Protein (CRP) was used to calculate DAS28. Higher scores represented higher disease activity.
Outcome measures
| Measure |
Tocilizumab
n=115 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Number of Participants Achieving Remission According to Disease Activity Score 28 (DAS28) at Weeks 24, 48, 72, and 96
Week 24 (n=115)
|
35 participants
|
|
Number of Participants Achieving Remission According to Disease Activity Score 28 (DAS28) at Weeks 24, 48, 72, and 96
Week 48 (n=95)
|
37 participants
|
|
Number of Participants Achieving Remission According to Disease Activity Score 28 (DAS28) at Weeks 24, 48, 72, and 96
Week 72 (n=73)
|
27 participants
|
|
Number of Participants Achieving Remission According to Disease Activity Score 28 (DAS28) at Weeks 24, 48, 72, and 96
Week 96 (n=72)
|
33 participants
|
SECONDARY outcome
Timeframe: Weeks 24, 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies number of participants with available data for specified category.
Remission was defined as DAS28 score \<2.6. The DAS28 score was a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity.
Outcome measures
| Measure |
Tocilizumab
n=115 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Percentage of Participants Achieving Remission According to DAS28 at Weeks 24, 48, 72, and 96
Week 24 (n=115)
|
30.4 percentage of participants
|
|
Percentage of Participants Achieving Remission According to DAS28 at Weeks 24, 48, 72, and 96
Week 48 (n=95)
|
38.9 percentage of participants
|
|
Percentage of Participants Achieving Remission According to DAS28 at Weeks 24, 48, 72, and 96
Week 72 (n=73)
|
37.0 percentage of participants
|
|
Percentage of Participants Achieving Remission According to DAS28 at Weeks 24, 48, 72, and 96
Week 96 (n=72)
|
45.8 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 24, 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies number of participants with available data for specified category.
The DAS28 score was a measure of the participant's disease activity calculated using the TJC \[28 joints\], SJC \[28 joints\], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity. EULAR Good response: DAS28 ≤3.2 and a change from Baseline \<-1.2. EULAR Moderate response: DAS28 greater than (\>) 3.2 to less than or equal to (≤) 5.1 or a change from Baseline \<-0.6 to greater than or equal to (≥) -1.2.
Outcome measures
| Measure |
Tocilizumab
n=114 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Percentage of Participants With DAS28 Good or Moderate European League Against Rheumatism (EULAR) Response at Weeks 24, 48, 72 and 96
Week 24 (n=114)
|
94.8 percentage of participants
|
|
Percentage of Participants With DAS28 Good or Moderate European League Against Rheumatism (EULAR) Response at Weeks 24, 48, 72 and 96
Week 48 (n=94)
|
94.7 percentage of participants
|
|
Percentage of Participants With DAS28 Good or Moderate European League Against Rheumatism (EULAR) Response at Weeks 24, 48, 72 and 96
Week 72 (n=73)
|
90.4 percentage of participants
|
|
Percentage of Participants With DAS28 Good or Moderate European League Against Rheumatism (EULAR) Response at Weeks 24, 48, 72 and 96
Week 96 (n=72)
|
94.5 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 24, 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies number of participants with available data for specified category.
SDAI was calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity (VAS 0-10 centimeter \[cm\]), and level of CRP. SDAI total score 0-86; higher scores = greater effect due to disease activity. Remission was defined as SDAI score ≤3.3. Low disease activity was defined as SDAI score ≤11.0.
Outcome measures
| Measure |
Tocilizumab
n=107 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Remission at Week 24 (n=107)
|
10.3 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 24 (n=107)
|
41.1 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Remission at Week 48 (n=86)
|
11.6 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 48 (n=86)
|
39.5 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Remission at Week 72 (n=60)
|
16.7 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 72 (n=60)
|
51.7 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Remission at Week 96 (n=72)
|
13.9 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 96 (n=72)
|
44.5 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 24, 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies number of participants with available data for specified category.
CDAI was calculated by a simple numerical sum of tender and swollen joint count (based on 28-joint assessment) and the patient and physician global disease assessment (VAS 0-10 cm). CDAI total score 0-76; higher scores = greater effect due to disease activity. Remission was defined as CDAI score ≤2.8. Low disease activity was defined as CDAI score ≤10.0.
Outcome measures
| Measure |
Tocilizumab
n=120 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Remission at Week 24 (n=120)
|
6.7 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 24 (n=120)
|
37.5 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Remission at Week 48 (n=97)
|
9.3 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 48 (n=97)
|
36.1 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Remission at Week 72 (n=75)
|
10.7 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 72 (n=75)
|
42.7 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Remission at Week 96 (n=80)
|
17.5 percentage of participants
|
|
Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96
Low Disease Activity at Week 96 (n=80)
|
47.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline; Weeks 24, 48, 72 and 96Population: ITT population. Here, 'n' signifies the number of participants with available data at specified timepoints.
68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from baseline indicated improvement.
Outcome measures
| Measure |
Tocilizumab
n=145 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in TJC At Weeks 24, 48, 72, and 96
Baseline (n=145)
|
22.8 tender joints
Standard Deviation 14.2
|
|
Change From Baseline in TJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 24 (n=124)
|
-13.4 tender joints
Standard Deviation 13.5
|
|
Change From Baseline in TJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 48 (n=99)
|
-15.2 tender joints
Standard Deviation 13.4
|
|
Change From Baseline in TJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 72 (n=79)
|
-13.9 tender joints
Standard Deviation 14.5
|
|
Change From Baseline in TJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 96 (n=84)
|
-14.5 tender joints
Standard Deviation 12.4
|
SECONDARY outcome
Timeframe: Baseline; Weeks 24, 48, 72 and 96Population: ITT population. Here, 'n' signifies the number of participants with available data at specified timepoints.
66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from baseline indicated improvement.
Outcome measures
| Measure |
Tocilizumab
n=145 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in SJC At Weeks 24, 48, 72, and 96
Baseline (n=145)
|
11.0 swollen joints
Standard Deviation 6.6
|
|
Change From Baseline in SJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 24 (n=124)
|
-7.3 swollen joints
Standard Deviation 6.7
|
|
Change From Baseline in SJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 48 (n=99)
|
-7.3 swollen joints
Standard Deviation 6.4
|
|
Change From Baseline in SJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 72 (n=79)
|
-7.6 swollen joints
Standard Deviation 6.8
|
|
Change From Baseline in SJC At Weeks 24, 48, 72, and 96
Change From Baseline at Week 96 (n=84)
|
-7.8 swollen joints
Standard Deviation 6.8
|
SECONDARY outcome
Timeframe: Weeks 24, 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number participants with available data for specified category.
ACR20 response: ≥20% improvement in TJC; ≥20% improvement in SJC; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ-DI\]); and either CRP or ESR. ACR50 response required ≥50% improvement in the above criteria and ACR70 response required ≥70% improvement in the above criteria.
Outcome measures
| Measure |
Tocilizumab
n=121 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR20: Week 24 (n=121)
|
48.8 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR20: Week 48 (n=96)
|
63.5 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR20: Week 72 (n=76)
|
60.5 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR20: Week 96 (n=81)
|
58.0 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR50: Week 24 (n=121)
|
24.8 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR50: Week 48 (n=96)
|
28.1 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR50: Week 72 (n=76)
|
34.2 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR50: Week 96 (n=81)
|
35.8 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR70: Week 24 (n=121)
|
11.6 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR70: Week 48 (n=96)
|
15.6 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR70: Week 72 (n=76)
|
21.1 percentage of partcipants
|
|
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96
ACR70: Week 96 (n=81)
|
21.0 percentage of partcipants
|
SECONDARY outcome
Timeframe: Baseline; Weeks 20, 44, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number participants with available data for specified category.
Outcome measures
| Measure |
Tocilizumab
n=138 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96
Baseline (n=138)
|
12.4 gram per deciliter
Standard Deviation 1.4
|
|
Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96
Change From Baseline at Week 20 (n=122)
|
0.7 gram per deciliter
Standard Deviation 1.0
|
|
Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96
Change From Baseline at Week 44 (n=91)
|
1.2 gram per deciliter
Standard Deviation 1.2
|
|
Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96
Change From Baseline at Week 72 (n=73)
|
1.0 gram per deciliter
Standard Deviation 1.1
|
|
Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96
Change From Baseline at Week 96 (n=80)
|
1.2 gram per deciliter
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number participants with available data for specified category.
Outcome measures
| Measure |
Tocilizumab
n=133 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
C-reactive Protein Level
Baseline (n=133)
|
2.8 milligram per deciliter
Standard Deviation 5.6
|
|
C-reactive Protein Level
Week 8 (n=114)
|
0.3 milligram per deciliter
Standard Deviation 1.2
|
|
C-reactive Protein Level
Week 16 (n=116)
|
0.3 milligram per deciliter
Standard Deviation 0.6
|
|
C-reactive Protein Level
Week 24 (n=112)
|
0.2 milligram per deciliter
Standard Deviation 0.6
|
|
C-reactive Protein Level
Week 36 (n=87)
|
0.3 milligram per deciliter
Standard Deviation 0.8
|
|
C-reactive Protein Level
Week 48 (n=89)
|
0.2 milligram per deciliter
Standard Deviation 0.3
|
|
C-reactive Protein Level
Week 72 (n=64)
|
0.2 milligram per deciliter
Standard Deviation 0.6
|
|
C-reactive Protein Level
Week 96 (n=75)
|
0.5 milligram per deciliter
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number participants with available data for specified category.
Outcome measures
| Measure |
Tocilizumab
n=138 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Erythrocyte Sedimentation Rate
Baseline (n=138)
|
45.3 millimeter per hour
Standard Deviation 27.1
|
|
Erythrocyte Sedimentation Rate
Week 8 (n=125)
|
10.6 millimeter per hour
Standard Deviation 11.6
|
|
Erythrocyte Sedimentation Rate
Week 16 (n=122)
|
11.3 millimeter per hour
Standard Deviation 14.9
|
|
Erythrocyte Sedimentation Rate
Week 24 (n=118)
|
8.8 millimeter per hour
Standard Deviation 8.8
|
|
Erythrocyte Sedimentation Rate
Week 36 (n=99)
|
9.8 millimeter per hour
Standard Deviation 12.0
|
|
Erythrocyte Sedimentation Rate
Week 48 (n=96)
|
8.3 millimeter per hour
Standard Deviation 10.7
|
|
Erythrocyte Sedimentation Rate
Week 72 (n=76)
|
9.0 millimeter per hour
Standard Deviation 9.5
|
|
Erythrocyte Sedimentation Rate
Week 96 (n=74)
|
7.4 millimeter per hour
Standard Deviation 8.4
|
SECONDARY outcome
Timeframe: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number participants with available data for specified category.
The mean score of pain as assessed by participants using a 100-mm horizontal VAS, where the left endpoint (0) indicated "No pain," and the right endpoint (100) indicated "Unbearable pain". Higher score indicated higher pain.
Outcome measures
| Measure |
Tocilizumab
n=143 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Participant Assessment of Pain (VAS)
Baseline (n=143)
|
70.3 mm
Standard Deviation 22.3
|
|
Participant Assessment of Pain (VAS)
Week 8 (n=136)
|
51.6 mm
Standard Deviation 26.7
|
|
Participant Assessment of Pain (VAS)
Week 16 (n=132)
|
53.0 mm
Standard Deviation 28.5
|
|
Participant Assessment of Pain (VAS)
Week 24 (n=123)
|
49.4 mm
Standard Deviation 26.8
|
|
Participant Assessment of Pain (VAS)
Week 36 (n=104)
|
44.7 mm
Standard Deviation 28.5
|
|
Participant Assessment of Pain (VAS)
Week 48 (n=100)
|
46.3 mm
Standard Deviation 28.8
|
|
Participant Assessment of Pain (VAS)
Week 72 (n=76)
|
42.3 mm
Standard Deviation 27.9
|
|
Participant Assessment of Pain (VAS)
Week 96 (n=82)
|
44.9 mm
Standard Deviation 28.0
|
SECONDARY outcome
Timeframe: Baseline; Weeks 24, 48, 72 and 96Population: ITT population. Number of participants analyzed=participants with available data for this endpoint. Here, 'n' signifies the number participants with available data for specified category.
HAQ: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Outcome measures
| Measure |
Tocilizumab
n=138 Participants
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96
Baseline (n=138)
|
1.8 units on a scale
Standard Deviation 0.7
|
|
Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96
Change From Baseline at Week 24 (n=112)
|
-0.4 units on a scale
Standard Deviation 0.6
|
|
Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96
Change From Baseline at Week 48 (n=92)
|
-0.4 units on a scale
Standard Deviation 0.6
|
|
Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96
Change From Baseline at Week 72 (n=73)
|
-0.4 units on a scale
Standard Deviation 0.6
|
|
Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96
Change From Baseline at Week 96 (n=81)
|
-0.5 units on a scale
Standard Deviation 0.6
|
Adverse Events
Tocilizumab
Serious adverse events
| Measure |
Tocilizumab
n=145 participants at risk
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Cardiac disorders
Angina unstable
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Cardiac disorders
Myocardial infarction (Acute myocardial infarction and Myocardial infarction)
|
1.4%
2/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Cardiac disorders
Pericardial effusion
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Gastrointestinal disorders
Duodenitis
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Gastrointestinal disorders
Gastric fistula
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Gastrointestinal disorders
Gastric perforation
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Gastrointestinal disorders
Gastritis
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
General disorders
Chest pain
|
1.4%
2/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
General disorders
Pelvic mass
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Hepatobiliary disorders
Cholangitis
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Cellulitis
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Diverticulitis
|
1.4%
2/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Otitis media chronic
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Pneumonia
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Urinary tract infection
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Investigations
Alanine aminotransferase/Aspartate aminotransferase elevations
|
1.4%
2/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Investigations
Catheterization cardiac
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast carcinoma
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Cerebrovascular accident
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Headache
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Hydrocephalus
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Syncope
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Transient ischaemic attack
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Renal and urinary disorders
Renal colic
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Skin and subcutaneous tissue disorders
Erysipelas
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Surgical and medical procedures
Cataract operation
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Surgical and medical procedures
Cystocele repair
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Surgical and medical procedures
Hernia repair
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Surgical and medical procedures
Hysterectomy
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Surgical and medical procedures
Lens extraction
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Surgical and medical procedures
Obesity surgery
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Immune system disorders
Type IV hypersensitivity reaction
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Vascular disorders
Hypertension
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Vascular disorders
Rectal hemorrhage
|
0.69%
1/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
Other adverse events
| Measure |
Tocilizumab
n=145 participants at risk
Participants received tocilizumab 8 mg/kg IV infusion every 4 weeks for a period of 96 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
22.1%
32/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.3%
12/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Upper respiratory tract infection
|
17.2%
25/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Viral Infection
|
9.7%
14/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Urinary tract infection
|
7.6%
11/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
9/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Investigations
Alanine aminotransferase/Aspartate aminotransferase elevations
|
32.4%
47/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
6.2%
9/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Musculoskeletal and connective tissue disorders
Exacerbation of rheumatoid arthritis
|
8.3%
12/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Nervous system disorders
Headache
|
5.5%
8/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.9%
10/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.5%
8/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
|
Gastrointestinal disorders
Nausea and Vomiting
|
6.2%
9/145 • From baseline up to 4 weeks after last dose of the study medication (up to Week 100)
|
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 only after the first publication or presentation that involves the Overall Study. The 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