Trial Outcomes & Findings for A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs. (NCT NCT00996203)
NCT ID: NCT00996203
Last Updated: 2018-03-29
Results Overview
HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Withdrawal Visit is the final visit prior to the withdrawal of the subject from the study.
COMPLETED
PHASE4
201 participants
Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit
2018-03-29
Participant Flow
Participant milestones
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) (but not more than 800 mg), intravenously (IV), every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Overall Study
STARTED
|
201
|
|
Overall Study
COMPLETED
|
194
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) (but not more than 800 mg), intravenously (IV), every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Protocol Violation
|
2
|
Baseline Characteristics
A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.
Baseline characteristics by cohort
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Age, Continuous
|
49.0 years
STANDARD_DEVIATION 12.0 • n=93 Participants
|
|
Sex: Female, Male
Female
|
174 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal VisitPopulation: Intent-to-Treat (ITT) population: All participants randomized in the study who received administration of at least one dose of the study drug and who had at least one efficacy assessment performed. n (number) = number of participants assessed at a specific visit.
HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Withdrawal Visit is the final visit prior to the withdrawal of the subject from the study.
Outcome measures
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Health Assessment Questionnaire (HAQ) Score
Week 12 (n=196)
|
1.08 units on a scale
Standard Deviation 0.62
|
|
Health Assessment Questionnaire (HAQ) Score
Week 0 (n=201)
|
1.93 units on a scale
Standard Deviation 0.60
|
|
Health Assessment Questionnaire (HAQ) Score
Week 4 (n=199)
|
1.49 units on a scale
Standard Deviation 0.65
|
|
Health Assessment Questionnaire (HAQ) Score
Week 8 (n=198)
|
1.22 units on a scale
Standard Deviation 0.63
|
|
Health Assessment Questionnaire (HAQ) Score
Week 16 (n=193)
|
1.00 units on a scale
Standard Deviation 0.60
|
|
Health Assessment Questionnaire (HAQ) Score
Week 20 (n=193)
|
0.90 units on a scale
Standard Deviation 0.61
|
|
Health Assessment Questionnaire (HAQ) Score
Week 24 (n=193)
|
0.84 units on a scale
Standard Deviation 0.62
|
|
Health Assessment Questionnaire (HAQ) Score
Withdrawal visit (n=6)
|
1.32 units on a scale
Standard Deviation 1.13
|
PRIMARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, and 24Population: ITT population:
HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Outcome measures
| Measure |
Tocilizumab
n=199 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 12 ≥50% (n=196)
|
42.3 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 4 ≥20% (n=199)
|
51.8 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 4 ≥50% (n=199)
|
15.6 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 4 ≥70% (n=199)
|
5.0 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 8 ≥20% (n=198)
|
72.2 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 8 ≥50% (n=198)
|
28.8 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 8 ≥70% (n=198)
|
13.6 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 12 ≥ 20% (n=196)
|
83.7 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 12 ≥70% (n=196)
|
18.9 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 16 ≥20% (n=193)
|
86.5 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 16 ≥50% (n=193)
|
51.3 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 16 ≥70% (n=193)
|
21.8 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 20 ≥20% (n=193)
|
89.6 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 20 ≥50% (n=193)
|
56.0 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 20 ≥70% (n=193)
|
34.2 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 24 ≥20% (n=193)
|
88.1 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 24 ≥50% (n=193)
|
61.7 percentage of participants
|
|
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Week 24 ≥70% (n=193)
|
38.3 percentage of participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: ITT population
HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Outcome measures
| Measure |
Tocilizumab
n=199 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Change in HAQ Score at Week 24
|
1.11 units on a scale
Standard Deviation 0.66
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
Participant's global assessment of pain was assessed using a 100-millimeter (mm) horizontal VAS (0 to 100 mm) with 0=pain absent and 100=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain.
Outcome measures
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Week 0 (n=201)
|
63.82 mm
Standard Deviation 16.71
|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Week 4 (n=199)
|
46.36 mm
Standard Deviation 20.57
|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Week 8 (n=198)
|
36.48 mm
Standard Deviation 18.94
|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Week 12 (n=196)
|
31.90 mm
Standard Deviation 19.83
|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Week 16 (n=193)
|
26.92 mm
Standard Deviation 18.87
|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Week 20 (n=193)
|
24.63 mm
Standard Deviation 19.09
|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Week 24 (n=193)
|
21.96 mm
Standard Deviation 18.87
|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Withdrawal visit (n=6)
|
34.50 mm
Standard Deviation 22.00
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Outcome measures
| Measure |
Tocilizumab
n=200 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Week 0 (n=200)
|
0.29 units on a scale
Standard Deviation 0.31
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Week 4 (n=199)
|
0.49 units on a scale
Standard Deviation 0.24
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Week 8 (n=198)
|
0.57 units on a scale
Standard Deviation 0.20
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Week 20 (n=193)
|
0.66 units on a scale
Standard Deviation 0.18
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Week 12 (n=196)
|
0.61 units on a scale
Standard Deviation 0.21
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Week 16 (n=193)
|
0.64 units on a scale
Standard Deviation 0.19
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Week 24 (n=193)
|
0.69 units on a scale
Standard Deviation 0.20
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Withdrawal visit (n=4)
|
0.61 units on a scale
Standard Deviation 0.07
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population
EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Minimum clinically significant change in EQ-5D corresponds to the parameter differences before and after treatment = 0.10. Graduations of assessment of the therapy efficacy by EQ-5D are: Difference (Δ) EQ-5D less than (\<)0.10 points: none; 0.10 less than or equal to (≤)Δ EQ-5D ≤0.24: minimal effect; 0.24≤ Δ EQ-5D \<0.31: satisfactory effect; Δ EQ-5D greater than or equal to (≥)0.31 points: pronounced effect.
Outcome measures
| Measure |
Tocilizumab
n=200 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Change in EQ-5D Score at Week 24 From Baseline
|
0.41 units on a scale
Standard Deviation 0.33
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.
Outcome measures
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
General Health Score as Assessed by EQ-5D VAS
Week 8 (n=198)
|
61.79 mm
Standard Deviation 43.45
|
|
General Health Score as Assessed by EQ-5D VAS
Week 12 (n=196)
|
66.13 mm
Standard Deviation 19.91
|
|
General Health Score as Assessed by EQ-5D VAS
Week 16 (n=193)
|
70.48 mm
Standard Deviation 19.39
|
|
General Health Score as Assessed by EQ-5D VAS
Week 24 (n=193)
|
76.22 mm
Standard Deviation 19.25
|
|
General Health Score as Assessed by EQ-5D VAS
Withdrawal visit (n=4)
|
60.50 mm
Standard Deviation 27.77
|
|
General Health Score as Assessed by EQ-5D VAS
Week 0 (n=201)
|
39.27 mm
Standard Deviation 18.03
|
|
General Health Score as Assessed by EQ-5D VAS
Week 4 (n=199)
|
50.93 mm
Standard Deviation 18.78
|
|
General Health Score as Assessed by EQ-5D VAS
Week 20 (n=192)
|
73.31 mm
Standard Deviation 19.58
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality. Positive response was defined as an increase of EQ-5D score by 0.1 or more i.e. it is a clinically significant increase.
Outcome measures
| Measure |
Tocilizumab
n=198 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
Week 4 (n=198)
|
42.9 percentage of Participants
|
|
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
Week 8 (n=198)
|
55.6 percentage of Participants
|
|
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
Week 12 (n=196)
|
60.2 percentage of Participants
|
|
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
Week 16 (n=193)
|
65.8 percentage of Participants
|
|
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
Week 20 (n=193)
|
68.4 percentage of Participants
|
|
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
Week 24 (n=193)
|
73.1 percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population
Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.
Outcome measures
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Change in General Health Assessed by VAS
|
37.3 mm
Standard Deviation 25.75
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
Outcome measures
| Measure |
Tocilizumab
n=199 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 24 (n=191)
|
2.637 units on a scale
Standard Deviation 1.157
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 0 (n=199)
|
6.748 units on a scale
Standard Deviation 0.852
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 4 (n=197)
|
4.665 units on a scale
Standard Deviation 1.227
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 8 (n=196)
|
3.777 units on a scale
Standard Deviation 1.279
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 12 (n=193)
|
3.347 units on a scale
Standard Deviation 1.208
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 16 (n=193)
|
2.956 units on a scale
Standard Deviation 1.230
|
|
Disease Activity Score Based on 28-Joint Count (DAS28)
Week 20 (n=192)
|
2.762 units on a scale
Standard Deviation 1.111
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population
Outcome measures
| Measure |
Tocilizumab
n=199 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Change in DAS28 Score From Baseline to Week 24
|
4.097 units on a scale
Standard Deviation 1.289
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR mm/hour, and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Disease activity: 0=remission (DAS28 less than \[\<\] 2.6), I=low (DAS28 less than or equal to \[≤\]2.6 to \<3.2), II=moderate (DAS28=3.2 to 5.1), III=high (DAS28 greater than \[\>\]5.1).
Outcome measures
| Measure |
Tocilizumab
n=199 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 0 high activity (n=199)
|
97.5 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 4 moderate activity (n=197)
|
52.8 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 8 high activity (n=196)
|
15.3 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 4 remission (n=197)
|
3.0 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 4 low activity (n=197)
|
9.6 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 4 high activity (n=197)
|
34.5 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 8 remission (n=196)
|
17.9 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 8 low activity (n=196)
|
15.3 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 8 moderate activity (n=196)
|
51.5 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 16 low activity (n=193)
|
19.2 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 16 moderate activity (n=193)
|
33.2 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 16 high activity (n=193)
|
6.2 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 0 moderate activity (n=199)
|
2.5 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 12 remission (n=193)
|
25.4 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 12 low activity (n=193)
|
22.8 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 12 moderate activity (n=193)
|
42.0 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 12 high activity (n=193)
|
9.8 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 16 remission (n=193)
|
41.5 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 20 remission (n=192)
|
44.8 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 20 low activity (n=192)
|
20.8 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 20 moderate activity (n=192)
|
30.7 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 20 high activity (n=192)
|
3.6 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 24 remission (n=191)
|
51.3 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 24, low activity (n=191)
|
19.4 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 20 moderate activity (n=191)
|
26.7 percentage of participants
|
|
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Week 24 high activity (n=191)
|
2.6 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
ACR20/50/70 response: ≥20%, ≥50%, or ≥70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) and in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase response: C-reactive protein (CRP) or ESR.
Outcome measures
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR20 Week 4
|
50.2 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR20 Week 8
|
76.1 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR20 Week 12
|
81.1 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR20 Week 16
|
89.6 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR20 Week 20
|
91.0 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR20 Week 24
|
89.1 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR50 Week 4
|
9.5 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR50 Week 8
|
27.4 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR50 Week 12
|
49.3 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR50 Week 16
|
61.2 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR50 Week 20
|
67.7 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR50 Week 24
|
70.6 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR70 Week 4
|
3.0 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR70 Week 8
|
10.0 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR70 Week 12
|
18.4 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR70 Week 16
|
26.9 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR70 Week 20
|
39.3 percentage of participants
|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
ACR70 Week 24
|
44.3 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
The DAS28-based EULAR response criteria were used to measure individual response as no effect, good effect, and moderate effect, depending on the extent of change from baseline and the level of disease activity reached. Good effect: change from baseline \>1.2 with DAS28 score ≤3.2; moderate effect: change from baseline \>1.2 with DAS28 score 3.2 to 5.1 or change from baseline \>0.6 to \<1.2 with DAS28 score \<3.2; no effect: change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 score \>5.1.
Outcome measures
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 4, No effect (n=195)
|
15.9 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 4, Moderate effect (n=195)
|
72.3 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 4, Good effect (n=195)
|
11.8 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 8, No effect (n=194)
|
5.7 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 8, Moderate effect (n=194)
|
61.9 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 8, Good effect (=194)
|
32.5 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 12, No effect (n=191)
|
4.7 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 12, Moderate effect (n=191)
|
47.6 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 12, Good effect (n=191)
|
47.6 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 16, No effect (n=191)
|
2.1 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 16, Moderate effect (n=191)
|
37.7 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 16, Good effect (n=191)
|
60.2 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 20, No effect (n=190)
|
0.5 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 20, Moderate effect (n=190)
|
34.2 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 20, Good effect (n=190)
|
65.3 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 24, No effect (n=189)
|
1.1 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 24, Moderate effect (n=189)
|
28.6 percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Week 24, Good effect (n=189)
|
70.4 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.
Outcome measures
| Measure |
Tocilizumab
n=200 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
C-Reactive Protein
Withdrawal visit (n=6)
|
7.00 mg/L
Standard Deviation 0.20
|
|
C-Reactive Protein
Week 0 (n=200)
|
33.51 mg/L
Standard Deviation 34.86
|
|
C-Reactive Protein
Week 4 (n=198)
|
8.67 mg/L
Standard Deviation 15.00
|
|
C-Reactive Protein
Week 8 (n=194)
|
7.62 mg/L
Standard Deviation 19.00
|
|
C-Reactive Protein
Week 12 (n=196)
|
5.43 mg/L
Standard Deviation 16.69
|
|
C-Reactive Protein
Week 16 (n=191)
|
4.66 mg/L
Standard Deviation 13.48
|
|
C-Reactive Protein
Week 20 (n=193)
|
4.92 mg/L
Standard Deviation 14.29
|
|
C-Reactive Protein
Week 24 (n=189)
|
4.78 mg/L
Standard Deviation 12.94
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, and 24Population: ITT Population; n=number of participants assessed at a specific visit.
ESR (mm/hr) is used to determine the acute phase response.
Outcome measures
| Measure |
Tocilizumab
n=201 Participants
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Erythrocyte Sedimentation Rate
Week 0 (n=201)
|
53.33 mm/hr
Standard Deviation 30.82
|
|
Erythrocyte Sedimentation Rate
Week 4 (n=198)
|
15.29 mm/hr
Standard Deviation 13.77
|
|
Erythrocyte Sedimentation Rate
Week 8 (n=197)
|
11.97 mm/hr
Standard Deviation 14.95
|
|
Erythrocyte Sedimentation Rate
Week 12 (n=193)
|
10.00 mm/hr
Standard Deviation 10.82
|
|
Erythrocyte Sedimentation Rate
Week 16 (n=193)
|
11.63 mm/hr
Standard Deviation 17.99
|
|
Erythrocyte Sedimentation Rate
Week 20 (n=193)
|
10.71 mm/hr
Standard Deviation 13.24
|
|
Erythrocyte Sedimentation Rate
Week 24 (n=193)
|
10.95 mm/hr
Standard Deviation 13.52
|
|
Erythrocyte Sedimentation Rate
Withdrawal visit (n=6)
|
15.00 mm/hr
Standard Deviation 4.00
|
Adverse Events
Tocilizumab
Serious adverse events
| Measure |
Tocilizumab
n=201 participants at risk
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Erysipelatous inflammation
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Nervous system disorders
Cervical myelopathy
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Localized infection
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Wound infection
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Acute pyelonephritis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Subcutaneous abscess
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Pneumonia
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Vascular disorders
Hemorrhagic anemia
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Vascular disorders
Venous thrombosis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Hepatobiliary disorders
Toxic hepatitis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Respiratory, thoracic and mediastinal disorders
Chronic bronchitis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Immune system disorders
Anaphylactic shock
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
Other adverse events
| Measure |
Tocilizumab
n=201 participants at risk
Participants received tocilizumab 8 mg/kg (but not more than 800 mg), IV, every 4 weeks for 24 weeks. Participants received a total of 6 infusions.
|
|---|---|
|
Blood and lymphatic system disorders
Lymphostasis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.5%
3/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Blood and lymphatic system disorders
Anaemia
|
1.00%
2/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.00%
2/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.00%
2/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Eye disorders
Keratitis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Gastrointestinal disorders
Diarrhoea
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Immune system disorders
Hypersensitivity
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Oral herpes
|
1.00%
2/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Respiratory tract infection
|
3.0%
6/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Respiratory tract infection viral
|
3.0%
6/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Acute tonsillitis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Pharyngitis
|
1.00%
2/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Onychomycosis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Infections and infestations
Tracheitis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Investigations
Blood pressure increased
|
1.00%
2/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Investigations
Transaminases increased
|
4.0%
8/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Investigations
Alanine aminotransferase increased
|
4.5%
9/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Investigations
Aspartate aminotransferase increased
|
2.5%
5/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Musculoskeletal and connective tissue disorders
Lower limb fracture
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Musculoskeletal and connective tissue disorders
Upper limb fracture
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Musculoskeletal and connective tissue disorders
Synovitis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Renal and urinary disorders
Pyelonephritis chronic
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Renal and urinary disorders
Renal colic
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Reproductive system and breast disorders
Prostatitis
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Skin and subcutaneous tissue disorders
Skin reactions
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Surgical and medical procedures
Tooth extraction
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Vascular disorders
Haemorrhoids
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
|
Vascular disorders
Hypertension
|
0.50%
1/201 • From baseline Visit up to 24 weeks or until withdrawal
|
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