Rheumatoid Arthritis
Conditions
Brief summary
This open-label single arm study will evaluate the efficacy and safety of tocilizumab added to traditional disease-modifying antirheumatic drugs (DMARDs) in patients with moderate to severe active rheumatoid arthritis and an inadequate response to DMARDs. Patients will receive tocilizumab 8 mg/kg by intravenous infusion every 4 weeks for 24 weeks, in addition to their current non-biologic DMARDs at stable doses. Anticipated time on study treatment is 24 weeks, and the target sample size is 200.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8 mg/kg iv every 4 weeks for 24 weeks
DRUGDMARDs (disease-modifying antirheumatic drugs)
stable doses at investigator's prescription
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>/= 18 years of age * moderate to severe active rheumatoid arthritis of \>/=6 months duration * inadequate clinical response to current non-biologic DMARDs * current DMARDs must be at stable dose for 8 weeks prior to study entry * oral corticosteroids (\</=10mg/day prednisone or equivalent) and NSAIDs must be at stable dose for \>/=4 weeks prior to screening
Exclusion criteria
* rheumatic autoimmune disease other than RA * history of or current inflammatory joint disease other than RA * previous treatment with any biologic DMARD * functional class IV as defined by the ACR classification * intra-articular or parenteral corticosteroids within 6 weeks prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Health Assessment Questionnaire (HAQ) Score | Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal 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. |
| Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment | Weeks 4, 8, 12, 16, 20, and 24 | 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. |
| Change in HAQ Score at Week 24 | Baseline and Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| General Health Score as Assessed by EQ-5D VAS | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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. |
| Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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. |
| Change in General Health Assessed by VAS | Baseline and Week 24 | 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. |
| Disease Activity Score Based on 28-Joint Count (DAS28) | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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. |
| Change in DAS28 Score From Baseline to Week 24 | Baseline and Week 24 | — |
| Pain Score as Assessed by Visual Analogue Scale (VAS) | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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. |
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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. |
| Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Weeks 4, 8, 12, 16, 20, and 24 | 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. |
| C-Reactive Protein | Weeks 4, 8, 12, 16, 20, and 24 | CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein. |
| Erythrocyte Sedimentation Rate | Weeks 4, 8, 12, 16, 20, and 24 | ESR (mm/hr) is used to determine the acute phase response. |
| Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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). |
| European Quality of Life - 5 Dimensions (EQ-5D) Score | Weeks 0, 4, 8, 12, 16, 20, and 24 | 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. |
| Change in EQ-5D Score at Week 24 From Baseline | Baseline and Week 24 | 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. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab 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. | 201 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 49.0 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 174 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 46 / 201 |
| serious Total, serious adverse events | 12 / 201 |
Outcome results
Primary
Change in HAQ Score at Week 24
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.
Time frame: Baseline and Week 24
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Change in HAQ Score at Week 24 | 1.11 units on a scale | Standard Deviation 0.66 |
p-value: <0.001t-test, 2 sided
Primary
Health Assessment Questionnaire (HAQ) Score
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.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Week 12 (n=196) | 1.08 units on a scale | Standard Deviation 0.62 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Week 0 (n=201) | 1.93 units on a scale | Standard Deviation 0.6 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Week 4 (n=199) | 1.49 units on a scale | Standard Deviation 0.65 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Week 8 (n=198) | 1.22 units on a scale | Standard Deviation 0.63 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Week 16 (n=193) | 1.00 units on a scale | Standard Deviation 0.6 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Week 20 (n=193) | 0.90 units on a scale | Standard Deviation 0.61 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Week 24 (n=193) | 0.84 units on a scale | Standard Deviation 0.62 |
| Tocilizumab | Health Assessment Questionnaire (HAQ) Score | Withdrawal visit (n=6) | 1.32 units on a scale | Standard Deviation 1.13 |
Primary
Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
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.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population:
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
| Tocilizumab | 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 |
Secondary
Change in DAS28 Score From Baseline to Week 24
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Change in DAS28 Score From Baseline to Week 24 | 4.097 units on a scale | Standard Deviation 1.289 |
p-value: <0.001t-test, 2 sided
Secondary
Change in EQ-5D Score at Week 24 From Baseline
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.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Change in EQ-5D Score at Week 24 From Baseline | 0.41 units on a scale | Standard Deviation 0.33 |
p-value: <0.001t-test, 2 sided
Secondary
Change in General Health Assessed by VAS
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.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab | Change in General Health Assessed by VAS | 37.3 mm | Standard Deviation 25.75 |
p-value: <0.001t-test, 2 sided
Secondary
C-Reactive Protein
CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | C-Reactive Protein | Week 0 (n=200) | 33.51 mg/L | Standard Deviation 34.86 |
| Tocilizumab | C-Reactive Protein | Week 4 (n=198) | 8.67 mg/L | Standard Deviation 15 |
| Tocilizumab | C-Reactive Protein | Week 8 (n=194) | 7.62 mg/L | Standard Deviation 19 |
| Tocilizumab | C-Reactive Protein | Week 12 (n=196) | 5.43 mg/L | Standard Deviation 16.69 |
| Tocilizumab | C-Reactive Protein | Week 16 (n=191) | 4.66 mg/L | Standard Deviation 13.48 |
| Tocilizumab | C-Reactive Protein | Week 20 (n=193) | 4.92 mg/L | Standard Deviation 14.29 |
| Tocilizumab | C-Reactive Protein | Week 24 (n=189) | 4.78 mg/L | Standard Deviation 12.94 |
| Tocilizumab | C-Reactive Protein | Withdrawal visit (n=6) | 7.00 mg/L | Standard Deviation 0.2 |
Secondary
Disease Activity Score Based on 28-Joint Count (DAS28)
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.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 0 (n=199) | 6.748 units on a scale | Standard Deviation 0.852 |
| Tocilizumab | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 4 (n=197) | 4.665 units on a scale | Standard Deviation 1.227 |
| Tocilizumab | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 8 (n=196) | 3.777 units on a scale | Standard Deviation 1.279 |
| Tocilizumab | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 12 (n=193) | 3.347 units on a scale | Standard Deviation 1.208 |
| Tocilizumab | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 16 (n=193) | 2.956 units on a scale | Standard Deviation 1.23 |
| Tocilizumab | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 20 (n=192) | 2.762 units on a scale | Standard Deviation 1.111 |
| Tocilizumab | Disease Activity Score Based on 28-Joint Count (DAS28) | Week 24 (n=191) | 2.637 units on a scale | Standard Deviation 1.157 |
Secondary
Erythrocyte Sedimentation Rate
ESR (mm/hr) is used to determine the acute phase response.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Erythrocyte Sedimentation Rate | Week 0 (n=201) | 53.33 mm/hr | Standard Deviation 30.82 |
| Tocilizumab | Erythrocyte Sedimentation Rate | Week 4 (n=198) | 15.29 mm/hr | Standard Deviation 13.77 |
| Tocilizumab | Erythrocyte Sedimentation Rate | Week 8 (n=197) | 11.97 mm/hr | Standard Deviation 14.95 |
| Tocilizumab | Erythrocyte Sedimentation Rate | Week 12 (n=193) | 10.00 mm/hr | Standard Deviation 10.82 |
| Tocilizumab | Erythrocyte Sedimentation Rate | Week 16 (n=193) | 11.63 mm/hr | Standard Deviation 17.99 |
| Tocilizumab | Erythrocyte Sedimentation Rate | Week 20 (n=193) | 10.71 mm/hr | Standard Deviation 13.24 |
| Tocilizumab | Erythrocyte Sedimentation Rate | Week 24 (n=193) | 10.95 mm/hr | Standard Deviation 13.52 |
| Tocilizumab | Erythrocyte Sedimentation Rate | Withdrawal visit (n=6) | 15.00 mm/hr | Standard Deviation 4 |
Secondary
European Quality of Life - 5 Dimensions (EQ-5D) Score
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.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Week 0 (n=200) | 0.29 units on a scale | Standard Deviation 0.31 |
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Week 4 (n=199) | 0.49 units on a scale | Standard Deviation 0.24 |
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Week 8 (n=198) | 0.57 units on a scale | Standard Deviation 0.2 |
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Week 12 (n=196) | 0.61 units on a scale | Standard Deviation 0.21 |
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Week 16 (n=193) | 0.64 units on a scale | Standard Deviation 0.19 |
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Week 20 (n=193) | 0.66 units on a scale | Standard Deviation 0.18 |
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Week 24 (n=193) | 0.69 units on a scale | Standard Deviation 0.2 |
| Tocilizumab | European Quality of Life - 5 Dimensions (EQ-5D) Score | Withdrawal visit (n=4) | 0.61 units on a scale | Standard Deviation 0.07 |
Secondary
General Health Score as Assessed by EQ-5D VAS
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.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Week 0 (n=201) | 39.27 mm | Standard Deviation 18.03 |
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Week 4 (n=199) | 50.93 mm | Standard Deviation 18.78 |
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Week 8 (n=198) | 61.79 mm | Standard Deviation 43.45 |
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Week 12 (n=196) | 66.13 mm | Standard Deviation 19.91 |
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Week 16 (n=193) | 70.48 mm | Standard Deviation 19.39 |
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Week 20 (n=192) | 73.31 mm | Standard Deviation 19.58 |
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Week 24 (n=193) | 76.22 mm | Standard Deviation 19.25 |
| Tocilizumab | General Health Score as Assessed by EQ-5D VAS | Withdrawal visit (n=4) | 60.50 mm | Standard Deviation 27.77 |
Secondary
Pain Score as Assessed by Visual Analogue Scale (VAS)
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.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Week 0 (n=201) | 63.82 mm | Standard Deviation 16.71 |
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Week 4 (n=199) | 46.36 mm | Standard Deviation 20.57 |
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Week 8 (n=198) | 36.48 mm | Standard Deviation 18.94 |
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Week 12 (n=196) | 31.90 mm | Standard Deviation 19.83 |
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Week 16 (n=193) | 26.92 mm | Standard Deviation 18.87 |
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Week 20 (n=193) | 24.63 mm | Standard Deviation 19.09 |
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Week 24 (n=193) | 21.96 mm | Standard Deviation 18.87 |
| Tocilizumab | Pain Score as Assessed by Visual Analogue Scale (VAS) | Withdrawal visit (n=6) | 34.50 mm | Standard Deviation 22 |
Secondary
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
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.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR20 Week 4 | 50.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR20 Week 8 | 76.1 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR20 Week 12 | 81.1 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR20 Week 16 | 89.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR20 Week 20 | 91.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR20 Week 24 | 89.1 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR50 Week 4 | 9.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR50 Week 8 | 27.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR50 Week 12 | 49.3 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR50 Week 16 | 61.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR50 Week 20 | 67.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR50 Week 24 | 70.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR70 Week 4 | 3.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR70 Week 8 | 10.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR70 Week 12 | 18.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR70 Week 16 | 26.9 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response | ACR70 Week 20 | 39.3 percentage of participants |
| Tocilizumab | 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
Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
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.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D | Week 4 (n=198) | 42.9 percentage of Participants |
| Tocilizumab | Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D | Week 8 (n=198) | 55.6 percentage of Participants |
| Tocilizumab | Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D | Week 12 (n=196) | 60.2 percentage of Participants |
| Tocilizumab | Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D | Week 16 (n=193) | 65.8 percentage of Participants |
| Tocilizumab | Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D | Week 20 (n=193) | 68.4 percentage of Participants |
| Tocilizumab | Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D | Week 24 (n=193) | 73.1 percentage of Participants |
Secondary
Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
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.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4, No effect (n=195) | 15.9 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4, Moderate effect (n=195) | 72.3 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 4, Good effect (n=195) | 11.8 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8, No effect (n=194) | 5.7 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8, Moderate effect (n=194) | 61.9 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 8, Good effect (=194) | 32.5 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12, No effect (n=191) | 4.7 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12, Moderate effect (n=191) | 47.6 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 12, Good effect (n=191) | 47.6 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16, No effect (n=191) | 2.1 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16, Moderate effect (n=191) | 37.7 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 16, Good effect (n=191) | 60.2 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20, No effect (n=190) | 0.5 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20, Moderate effect (n=190) | 34.2 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 20, Good effect (n=190) | 65.3 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24, No effect (n=189) | 1.1 percentage of participants |
| Tocilizumab | Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | Week 24, Moderate effect (n=189) | 28.6 percentage of participants |
| Tocilizumab | 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
Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
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).
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; n=number of participants assessed at a specific visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 0 moderate activity (n=199) | 2.5 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 0 high activity (n=199) | 97.5 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 4 remission (n=197) | 3.0 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 4 low activity (n=197) | 9.6 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 4 moderate activity (n=197) | 52.8 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 4 high activity (n=197) | 34.5 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 8 remission (n=196) | 17.9 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 8 low activity (n=196) | 15.3 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 8 moderate activity (n=196) | 51.5 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 8 high activity (n=196) | 15.3 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 12 remission (n=193) | 25.4 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 12 low activity (n=193) | 22.8 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 12 moderate activity (n=193) | 42.0 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 12 high activity (n=193) | 9.8 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 16 remission (n=193) | 41.5 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 16 low activity (n=193) | 19.2 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 16 moderate activity (n=193) | 33.2 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 16 high activity (n=193) | 6.2 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 20 remission (n=192) | 44.8 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 20 low activity (n=192) | 20.8 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 20 moderate activity (n=192) | 30.7 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 20 high activity (n=192) | 3.6 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 24 remission (n=191) | 51.3 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 24, low activity (n=191) | 19.4 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 20 moderate activity (n=191) | 26.7 percentage of participants |
| Tocilizumab | Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment | Week 24 high activity (n=191) | 2.6 percentage of participants |