Rheumatoid Arthritis
Conditions
Brief summary
This 2 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with active rheumatoid arthritis who currently have an inadequate response to DMARD therapy. Patients will be randomized 2:1 to receive tocilizumab 8mg/kg iv or placebo iv every 4 weeks, in conjunction with stable DMARD therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks for 24 weeks
DRUGPlacebo
iv every 4 weeks for 24 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* adult patients, 18-70 years of age; * rheumatoid arthritis for \>= 6 months; * receiving permitted DMARDs, at a stable dose, for \>= 8 weeks prior to baseline; * current inadequate clinical response to DMARDs.
Exclusion criteria
* major surgery, including joint surgery, within 8 weeks before entering study, or planned major surgery within 6 months following randomization; * rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis; * unsuccessful treatment with an anti-TNF agent; * previous treatment with tocilizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 | Week 24 | To achieve an ACR20 response required at least a 20% improvement, compared with baseline, in both (tender joints count)TJC and (swollen joints count) SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire disease index (HAQ-DI) and C-reactive protein (CRP). CRP was used primarily for the calculation of the ACR response; if missing, Erythrocyte Sedimentation Rate (ESR) was substituted. ITT sensitivity analysis was carried out using an alternative imputation method (last observation carried forward \[LOCF\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24 | Baseline and Week 24 | The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A negative change from Baseline indicated improvement. |
| Percentage of Participants With ACR50 and ACR70 Responses at Week 24 | Week 24 | To achieve an ACR50 or ACR 70 response required at least a 50% or 70% improvement, compared with baseline in both TJC and SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, HAQ-DI and CRP. CRP was used primarily for the calculation of the ACR response; if missing, ESR was substituted. |
| Number of Participants Who Received Escape Therapy | 24 Weeks | Participants who did not achieve a 20% improvement from baseline in both SJC and TJC at week 16 could, if requested and deemed necessary by the investigator, receive escape therapy, comprising adjustment of the background DMARD dose and/or treatment with a different traditional DMARD. |
| Change in Tender and Swollen Joint Counts From Baseline to Week 24 | Baseline and Week 24 | 68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68. 66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. |
| Change in Participant's Global Assessment of Pain From Baseline to Week 24 | Baseline and Week 24 | The participants assessed their pain on a 0 to 100 mm VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. A negative change indicated improvement. |
| Change in C-Reactive Protein From Baseline to Week 24 | Baseline and Week 24 | The serum concentration of CRP an acute phase inflammatory marker, is measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement. |
| Change in ESR From Baseline to Week 24 | Baseline and Week 24 | The ESR was measured in mm/hour. A reduction in the level is considered an improvement. |
| Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24 | Baseline and Week 24 | The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity). |
| Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score | Baseline and Week 24 | FACIT-F is a 13-item questionnaire. Patients 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 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 (worse score) to 52 (better score). A higher score reflects an improvement in health status. |
| Mean Rheumatoid Factor at Baseline and Week 24 | Baseline and 24 Weeks | Rheumatoid factor (RF) is a disease characteristic and more than 85% of the participants studied were positive for the factor. These data are from patients who were RF positive. RF level was reported in international units/milliliter (IU/mL). A positive RF= \>15 IU/mL. |
| Change in Hemoglobin From Baseline to Week 24 | Baseline and 24 Weeks | Levels of hemoglobin were determined in grams/liter (g/L)as a measure of anemia in participants |
| Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24 | Baseline and 24 Weeks | HAQ-DI is a self-completed participant questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement. |
| Percentage of Participants With ACR20 Response by First Week of Onset | Weeks 2, 4, 8, 12, 16, 20, and 24 | ACR 20 responses are summarized by first onset as a percentage of the total number of responders at week 24. The number of participants first achieving an ACR20 response at each time point is represented by treatment arm as a proportion of the total number of participants that had an ACR20 response at Week 24 using n as the denominator. |
| Time to First Low Disease Activity | Weeks 2, 4, 8, 12, 16, 20, and 24 | Time to Low disease activity was calculated as the number of days from the first dose of drug administration to the date of first achievement of DAS28≤3.2. |
| Time to First Remission | Weeks 2, 4, 8, 12, 16, 20, and 24 | Time to first Remission was calculated as the number of days from the date of first dose of study drug administration to the date of first achievement of DAS\<2.6 |
| Percentage of Participants With Low Disease Activity and in Clinical Remission | Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 | DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, ESR 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. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo + DMARDs Participants received placebo intravenously every 4 weeks up to 24 weeks in combination with stable DMARD therapy | 69 |
| Tocilizumab + DMARDs Participants received tocilizumab 8 mg/kg intravenously every 4 weeks up to 24 weeks in combination with stable DMARD therapy | 139 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo + DMARDs | Tocilizumab + DMARDs | Total |
|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 11.68 | 46.8 years STANDARD_DEVIATION 11.01 | 47.1 years STANDARD_DEVIATION 11.22 |
| Sex: Female, Male Female | 55 Participants | 120 Participants | 175 Participants |
| Sex: Female, Male Male | 14 Participants | 19 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 68 | 59 / 139 |
| serious Total, serious adverse events | 4 / 68 | 1 / 139 |
Outcome results
Primary
Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24
To achieve an ACR20 response required at least a 20% improvement, compared with baseline, in both (tender joints count)TJC and (swollen joints count) SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire disease index (HAQ-DI) and C-reactive protein (CRP). CRP was used primarily for the calculation of the ACR response; if missing, Erythrocyte Sedimentation Rate (ESR) was substituted. ITT sensitivity analysis was carried out using an alternative imputation method (last observation carried forward \[LOCF\]).
Time frame: Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + DMARDs | Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 | ITT Population | 24.6 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 | ITT Population (Sensitivity) | 24.6 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 | ITT Population | 69.8 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 | ITT Population (Sensitivity) | 73.4 Percentage of Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
FACIT-F is a 13-item questionnaire. Patients 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 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 (worse score) to 52 (better score). A higher score reflects an improvement in health status.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score | 2.08 units on a scale | Standard Deviation 7.684 |
| Tocilizumab + DMARDs | Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score | 6.51 units on a scale | Standard Deviation 9.244 |
p-value: 0.000395% CI: [1.8, 5.9]ANCOVA
Secondary
Change in C-Reactive Protein From Baseline to Week 24
The serum concentration of CRP an acute phase inflammatory marker, is measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change in C-Reactive Protein From Baseline to Week 24 | -0.083 mg/dL | Standard Deviation 2.31 |
| Tocilizumab + DMARDs | Change in C-Reactive Protein From Baseline to Week 24 | -1.865 mg/dL | Standard Deviation 2.152 |
p-value: <0.000195% CI: [-2.1464, -1.3303]ANCOVA
Secondary
Change in ESR From Baseline to Week 24
The ESR was measured in mm/hour. A reduction in the level is considered an improvement.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change in ESR From Baseline to Week 24 | -4.4 mm/hour | Standard Deviation 22.46 |
| Tocilizumab + DMARDs | Change in ESR From Baseline to Week 24 | -42.7 mm/hour | Standard Deviation 26.23 |
p-value: <0.000195% CI: [-44.7, -33.7]ANCOVA
Secondary
Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24
HAQ-DI is a self-completed participant questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Time frame: Baseline and 24 Weeks
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24 | -0.06 units on a scale | Standard Deviation 0.522 |
| Tocilizumab + DMARDs | Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24 | -0.52 units on a scale | Standard Deviation 0.554 |
p-value: <0.000195% CI: [-0.56, -0.28]ANCOVA
Secondary
Change in Hemoglobin From Baseline to Week 24
Levels of hemoglobin were determined in grams/liter (g/L)as a measure of anemia in participants
Time frame: Baseline and 24 Weeks
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change in Hemoglobin From Baseline to Week 24 | -1.0 g/L | Standard Deviation 11.7 |
| Tocilizumab + DMARDs | Change in Hemoglobin From Baseline to Week 24 | 12.0 g/L | Standard Deviation 14.1 |
p-value: <0.000195% CI: [9.125, 16.786]ANCOVA
Secondary
Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24
The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the participant. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as maximum disease activity (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24 | -8.7 mm | Standard Deviation 26.27 |
| Tocilizumab + DMARDs | Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24 | -26.4 mm | Standard Deviation 24.69 |
p-value: <0.000195% CI: [-25.3, -12.9]ANCOVA
Secondary
Change in Participant's Global Assessment of Pain From Baseline to Week 24
The participants assessed their pain on a 0 to 100 mm VAS. The left-hand extreme of the line equals 0 mm, and is described as no pain and the right-hand extreme equals 100 mm as unbearable pain. A negative change indicated improvement.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change in Participant's Global Assessment of Pain From Baseline to Week 24 | -5.9 mm | Standard Deviation 23.97 |
| Tocilizumab + DMARDs | Change in Participant's Global Assessment of Pain From Baseline to Week 24 | -23.5 mm | Standard Deviation 25.78 |
p-value: <0.000195% CI: [-25.2, -12.7]ANCOVA
Secondary
Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24
The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as maximum disease activity (maximum arthritis disease activity).
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + DMARDs | Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24 | -9.9 mm | Standard Deviation 22.61 |
| Tocilizumab + DMARDs | Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24 | -29.1 mm | Standard Deviation 22.43 |
p-value: <0.000195% CI: [-24.5, -14]ANCOVA
Secondary
Change in Tender and Swollen Joint Counts From Baseline to Week 24
68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68. 66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + DMARDs | Change in Tender and Swollen Joint Counts From Baseline to Week 24 | Swollen Joint Count | -4.5 Joints | Standard Deviation 11.61 |
| Placebo + DMARDs | Change in Tender and Swollen Joint Counts From Baseline to Week 24 | Tender Joint Count | -6.2 Joints | Standard Deviation 12.31 |
| Tocilizumab + DMARDs | Change in Tender and Swollen Joint Counts From Baseline to Week 24 | Swollen Joint Count | -9.9 Joints | Standard Deviation 9.26 |
| Tocilizumab + DMARDs | Change in Tender and Swollen Joint Counts From Baseline to Week 24 | Tender Joint Count | -16.5 Joints | Standard Deviation 12.06 |
Comparison: Placebo + DMARDs Vs Tocilizumab + DMARDs analysis for Swollen Joint Countp-value: <0.000195% CI: [-6.6, -2.8]ANCOVA
Comparison: Placebo + DMARDs Vs Tocilizumab + DMARDs analysis for Tender Joint Countp-value: <0.000195% CI: [-11.3, -6.1]ANCOVA
Secondary
Mean Rheumatoid Factor at Baseline and Week 24
Rheumatoid factor (RF) is a disease characteristic and more than 85% of the participants studied were positive for the factor. These data are from patients who were RF positive. RF level was reported in international units/milliliter (IU/mL). A positive RF= \>15 IU/mL.
Time frame: Baseline and 24 Weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + DMARDs | Mean Rheumatoid Factor at Baseline and Week 24 | Baseline, n = 61, 125 | 179.5 IU/mL | Standard Deviation 199.57 |
| Placebo + DMARDs | Mean Rheumatoid Factor at Baseline and Week 24 | Week 24, n = 57, 118 | 198.6 IU/mL | Standard Deviation 277.06 |
| Tocilizumab + DMARDs | Mean Rheumatoid Factor at Baseline and Week 24 | Baseline, n = 61, 125 | 262.2 IU/mL | Standard Deviation 360.39 |
| Tocilizumab + DMARDs | Mean Rheumatoid Factor at Baseline and Week 24 | Week 24, n = 57, 118 | 204.6 IU/mL | Standard Deviation 365.25 |
p-value: 0.059995% CI: [-139.5, 2.9]ANCOVA
Secondary
Number of Participants Who Received Escape Therapy
Participants who did not achieve a 20% improvement from baseline in both SJC and TJC at week 16 could, if requested and deemed necessary by the investigator, receive escape therapy, comprising adjustment of the background DMARD dose and/or treatment with a different traditional DMARD.
Time frame: 24 Weeks
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + DMARDs | Number of Participants Who Received Escape Therapy | 4 Number of participants |
| Tocilizumab + DMARDs | Number of Participants Who Received Escape Therapy | 0 Number of participants |
Secondary
Percentage of Participants With ACR20 Response by First Week of Onset
ACR 20 responses are summarized by first onset as a percentage of the total number of responders at week 24. The number of participants first achieving an ACR20 response at each time point is represented by treatment arm as a proportion of the total number of participants that had an ACR20 response at Week 24 using n as the denominator.
Time frame: Weeks 2, 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 8 | 5.9 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 16 | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 4 | 23.5 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 20 | 17.6 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 12 | 17.6 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 24 | 17.6 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 2 | 17.6 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 24 | 3.1 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 2 | 21.6 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 4 | 22.7 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 8 | 30.9 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 12 | 15.5 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 16 | 5.2 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR20 Response by First Week of Onset | First onset at Week 20 | 1.0 Percentage of Participants |
Secondary
Percentage of Participants With ACR50 and ACR70 Responses at Week 24
To achieve an ACR50 or ACR 70 response required at least a 50% or 70% improvement, compared with baseline in both TJC and SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, HAQ-DI and CRP. CRP was used primarily for the calculation of the ACR response; if missing, ESR was substituted.
Time frame: Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + DMARDs | Percentage of Participants With ACR50 and ACR70 Responses at Week 24 | ACR 50 | 10.1 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With ACR50 and ACR70 Responses at Week 24 | ACR 70 | 2.9 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR50 and ACR70 Responses at Week 24 | ACR 50 | 38.8 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With ACR50 and ACR70 Responses at Week 24 | ACR 70 | 12.9 Percentage of Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: 0.0345Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Low Disease Activity and in Clinical Remission
DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, ESR 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. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (\>)3.2 to 5.1 = moderate to high disease activity.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24
Population: ITT Population; n=number of participants analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 2 Remission first achieved (n= 67,138) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Baseline Low Disease Activity (n= 69,139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Baseline Remission (n=69, 139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Baseline Remission first achieved (n=69, 139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 2 Low Disease Activity (n= 67,138) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 2 Remission (n= 67,138) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 4 Low Disease Activity (n= 67,139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 4 Remission (n=67,139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 4 Remission first achieved (n=67,139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 8 Low Disease Activity (n= 67,139) | 1.5 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 8 Remission (n=67,139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 8 Remission first achieved (n=67,139) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 12 Low Disease Activity (n=65,138) | 3.1 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 12 Remission (n=65,138) | 3.1 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 12 Remission first achieved (n=65,138) | 3.1 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 16 Low Disease Activity (n=65,136) | 6.2 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 16 Remission (n=65,136) | 1.5 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 16 Remission first achieved (n=65,136) | 1.5 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 20 Low Disease Activity (n=63,134) | 3.2 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 20 Remission (n=63,134) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 20 Remission first achieved (n=63,134) | 0 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 24 Low Disease Activity (n=64,131) | 4.7 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 24 Remission (n=64,131) | 3.1 Percentage of Participants |
| Placebo + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 24 Remission first achieved (n=64,131) | 1.6 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 24 Remission (n=64,131) | 30.5 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 4 Remission (n=67,139) | 5.0 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 12 Low Disease Activity (n=65,138) | 37.7 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Baseline Low Disease Activity (n= 69,139) | 0 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 20 Low Disease Activity (n=63,134) | 46.3 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Baseline Remission (n=69, 139) | 0 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 12 Remission (n=65,138) | 21.0 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Baseline Remission first achieved (n=69, 139) | 0 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 24 Low Disease Activity (n=64,131) | 46.6 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 2 Low Disease Activity (n= 67,138) | 2.2 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 12 Remission first achieved (n=65,138) | 10.1 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 2 Remission (n= 67,138) | 0.7 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 2 Remission first achieved (n= 67,138) | 0.7 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 20 Remission (n=63,134) | 29.1 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 4 Low Disease Activity (n= 67,139) | 12.9 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 16 Low Disease Activity (n=65,136) | 39.0 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 24 Remission first achieved (n=64,131) | 4.6 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 4 Remission first achieved (n=67,139) | 5.0 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 16 Remission (n=65,136) | 24.3 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 8 Low Disease Activity (n= 67,139) | 24.5 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 20 Remission first achieved (n=63,134) | 7.5 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 8 Remission (n=67,139) | 12.9 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 16 Remission first achieved (n=65,136) | 7.4 Percentage of Participants |
| Tocilizumab + DMARDs | Percentage of Participants With Low Disease Activity and in Clinical Remission | Week 8 Remission first achieved (n=67,139) | 8.6 Percentage of Participants |
Secondary
Time to First Low Disease Activity
Time to Low disease activity was calculated as the number of days from the first dose of drug administration to the date of first achievement of DAS28≤3.2.
Time frame: Weeks 2, 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + DMARDs | Time to First Low Disease Activity | NA Days |
| Tocilizumab + DMARDs | Time to First Low Disease Activity | 139 Days |
Secondary
Time to First Remission
Time to first Remission was calculated as the number of days from the date of first dose of study drug administration to the date of first achievement of DAS\<2.6
Time frame: Weeks 2, 4, 8, 12, 16, 20, and 24
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + DMARDs | Time to First Remission | NA Days |
| Tocilizumab + DMARDs | Time to First Remission | NA Days |