Rheumatoid Arthritis
Conditions
Brief summary
This randomized, parallel-group, placebo-controlled, multicenter study will evaluate the reduction in disease activity and the safety of tocilizumab (RoActemra/Actemra) in combination with traditional disease-modifying anti-rheumatic drugs (DMARDs) in patients with active, moderate to severe rheumatoid arthritis. In the double-blind part of the study, patients will be randomized to receive either 162 mg tocilizumab or placebo subcutaneously every 2 weeks for 24 weeks using a pre-filled syringe. In the open-label part of the study, patients will be randomized to receive 162 mg tocilizumab subcutaneously every 2 weeks from Week 24 to Week 96 using a pre-filled syringe or an auto-injector.
Interventions
DRUGTocilizumab 162 mg
Tocilizumab will be supplied in a ready-to-use, single-use, pre-filled syringe. Patients and/or caregivers will be trained to administer the injection.
DRUGPlacebo
Placebo will be supplied in a ready-to-use, single-use, pre-filled syringe. Patients and/or caregivers will be trained to administer the injection.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, ≥ years of age. * Moderate to severe rheumatoid arthritis of ≥ 6 months duration. * Receiving treatment on an outpatient basis. * Swollen joint count (SJC) ≥ 6 (66 joint count) and tender joint count (TJC)≥ 8 (68 joint count) at screening and study start. * On a stable dose of disease-modifying anti-rheumatic drugs for at least 8 weeks prior to study start.
Exclusion criteria
* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. * Rheumatic autoimmune disease other than rheumatoid arthritis, Secondary Sjögren's Syndrome with rheumatoid arthritis is allowed. * Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis. * Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16 years. * Prior history of or current inflammatory joint disease other than rheumatoid arthritis. * History of malignancy, active or recurrent infections, positive to hepatitis B surface antigen or hepatitis C antibody, active tuberculosis, serious allergy to biologics, or a history of diverticular disease or other symptomatic GI conditions that might predispose to perforations. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24 | Baseline to Week 24 | A patient had an ACR20 response if there was at least a 20% improvement, ie, reduction from baseline, in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, left end=no disease activity \[symptom-free and no arthritis symptoms\], right end=maximum disease activity; patient assessment of pain in previous 24 hours on a VAS (left end=no pain and right end=unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and acute-phase reactant (either C-reactive protein or erythrocyte sedimentation rate). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of ACR20, ACR50, and ACR70 Responses | Baseline to Week 24 | Time to first ACR response was calculated as the number of days between the date of the first ACR response minus the date of the first dose of study drug. Median days are reported. |
| Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24 | Baseline to Week 24 | Joints (28 joints) will be assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation on physical examination. |
| Change From Baseline in C-reactive Protein at Week 24 | Baseline to Week 24 | — |
| Change From Baseline in Erythrocyte Sedimentation Rate at Week 24 | Baseline to Week 24 | — |
| Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score | Baseline to Week 24 | Patients and physicians assessed the patient's disease activity in the previous 24 hours on a 100 mm visual analog scale, where the extreme left end of the line represented no disease activity (symptom-free and no arthritis symptoms) and the extreme right end represented maximum disease activity. Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity. |
| Change From Baseline in the Patient's Pain Visual Analog Score | Baseline to Week 24 | Patients assessed their pain in the previous 24 hours on a visual analog scale, where the extreme left end of the line represented no pain and the extreme right end represented unbearable pain. Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain. |
| Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 | Baseline to Week 24 | The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. |
| Percentage of Patients With ACR50 and ACR70 Responses at Week 24 | Baseline to Week 24 | A patient had an ACR50 response if there was at least a 50% improvement in the ACR scores. A patient had an ACR70 response if there was at least a 70% improvement in the ACR scores. |
| Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24 | Baseline to Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. |
| Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24 | Baseline to Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. |
| Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24 | Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. |
| Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | Baseline to Week 24 | Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score \> 3.2 to ≤ 5.1, a change from baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score \> 5.1, a change from baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores \> 3.2. |
| Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24 | Baseline to Week 24 | The degree of joint damage was assessed using the van der Heijde modified total Sharp score (mTSS). The methodology quantifies the extent of bone erosions for 44 joints and joint space narrowing (JSN) for 42 joints, with higher scores representing greater damage. The independent read of X-ray images was performed by 2 primary readers. In case of discrepancy between the 2 primary readers, an adjudicator was involved. The mTSS can range from 0 to 448 with a higher score indicating more joint damage. A negative change score indicates improvement. |
| Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24 | Baseline to Week 24 | The SF-36 Health Survey uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A positive change score indicates an improvement in HRQoL. |
| Change From Baseline in Hemoglobin at Week 24 | Baseline to Week 24 | — |
| Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24 | Baseline to Week 24 | The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Colombia, Greece, Guatemala, Hungary, Israel, Malaysia, Mexico, New Zealand, Panama, Philippines, Poland, Russia, South Africa, Spain, Switzerland, Thailand, United States
Participant flow
Pre-assignment details
Of the 656 patients randomized into the study (437 to the tocilizumab arm and 219 to the placebo arm), 438 patients received tocilizumab as their first dose and 218 received placebo as their first dose because of a dose administration error with 1 patient.
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab 162 mg sc Patients received tocilizumab 162 mg subcutaneously (sc) every 2 weeks for 24 weeks. | 437 |
| Placebo sc Patients received placebo subcutaneously (sc) every 2 weeks for 24 weeks. | 218 |
| Total | 655 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Treatment Period | Adverse Event (Except Anaphylaxis) | 9 | 3 | 0 | 0 |
| Double-blind Treatment Period | Death | 2 | 0 | 0 | 0 |
| Double-blind Treatment Period | Escape | 2 | 2 | 0 | 0 |
| Double-blind Treatment Period | Lack of Efficacy | 1 | 2 | 0 | 0 |
| Double-blind Treatment Period | Lost to Follow-up | 4 | 0 | 0 | 0 |
| Double-blind Treatment Period | Physician Decision | 1 | 0 | 0 | 0 |
| Double-blind Treatment Period | Withdrawal by Subject | 9 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Tocilizumab 162 mg sc | Placebo sc | Total |
|---|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 11.49 | 52.0 years STANDARD_DEVIATION 11.67 | 52.1 years STANDARD_DEVIATION 11.54 |
| Sex: Female, Male Female | 375 Participants | 180 Participants | 555 Participants |
| Sex: Female, Male Male | 62 Participants | 38 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 212 / 437 | 65 / 218 | 89 / 168 | 35 / 61 | 33 / 59 |
| serious Total, serious adverse events | 36 / 437 | 8 / 218 | 17 / 168 | 2 / 61 | 0 / 59 |
Outcome results
Primary
Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24
A patient had an ACR20 response if there was at least a 20% improvement, ie, reduction from baseline, in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, left end=no disease activity \[symptom-free and no arthritis symptoms\], right end=maximum disease activity; patient assessment of pain in previous 24 hours on a VAS (left end=no pain and right end=unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and acute-phase reactant (either C-reactive protein or erythrocyte sedimentation rate).
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab 162 mg sc | Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24 | 60.9 Percentage of patients |
| Placebo sc | Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24 | 31.5 Percentage of patients |
p-value: <0.00195% CI: [22, 37]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in C-reactive Protein at Week 24
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in C-reactive Protein at Week 24 | -1.7 mg/dL | Standard Deviation 2.6 |
| Placebo sc | Change From Baseline in C-reactive Protein at Week 24 | -0.1 mg/dL | Standard Deviation 1.8 |
Secondary
Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24 | -3.3 Units on a scale | Standard Deviation 1.4 |
| Placebo sc | Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24 | -1.8 Units on a scale | Standard Deviation 1.3 |
Secondary
Change From Baseline in Erythrocyte Sedimentation Rate at Week 24
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in Erythrocyte Sedimentation Rate at Week 24 | -36.4 mm/hr | Standard Deviation 23.6 |
| Placebo sc | Change From Baseline in Erythrocyte Sedimentation Rate at Week 24 | -9.5 mm/hr | Standard Deviation 22.7 |
Secondary
Change From Baseline in Hemoglobin at Week 24
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in Hemoglobin at Week 24 | 11.0 g/L | Standard Deviation 12.6 |
| Placebo sc | Change From Baseline in Hemoglobin at Week 24 | 0.0 g/L | Standard Deviation 7.1 |
Secondary
Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24
Joints (28 joints) will be assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation on physical examination.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24 | Tender Joint Count | -14.8 Joint count | Standard Deviation 15 |
| Tocilizumab 162 mg sc | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24 | Swollen Joint Count | -9.6 Joint count | Standard Deviation 9.7 |
| Placebo sc | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24 | Tender Joint Count | -8.1 Joint count | Standard Deviation 14.2 |
| Placebo sc | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24 | Swollen Joint Count | -5.9 Joint count | Standard Deviation 10.2 |
Secondary
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 | -0.5 Units on a scale | Standard Deviation 0.6 |
| Placebo sc | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 | -0.3 Units on a scale | Standard Deviation 0.6 |
Secondary
Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score
Patients and physicians assessed the patient's disease activity in the previous 24 hours on a 100 mm visual analog scale, where the extreme left end of the line represented no disease activity (symptom-free and no arthritis symptoms) and the extreme right end represented maximum disease activity. Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score | Patient's Global Assessment VAS, N=346, 123 | -32.0 Units on a scale | Standard Deviation 27.6 |
| Tocilizumab 162 mg sc | Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score | Physician's Global Assessment VAS, N=348, 124 | -36.9 Units on a scale | Standard Deviation 22.5 |
| Placebo sc | Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score | Patient's Global Assessment VAS, N=346, 123 | -20.9 Units on a scale | Standard Deviation 25.2 |
| Placebo sc | Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score | Physician's Global Assessment VAS, N=348, 124 | -30.7 Units on a scale | Standard Deviation 25.8 |
Secondary
Change From Baseline in the Patient's Pain Visual Analog Score
Patients assessed their pain in the previous 24 hours on a visual analog scale, where the extreme left end of the line represented no pain and the extreme right end represented unbearable pain. Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in the Patient's Pain Visual Analog Score | -28.1 Units on a scale | Standard Deviation 27.2 |
| Placebo sc | Change From Baseline in the Patient's Pain Visual Analog Score | -15.0 Units on a scale | Standard Deviation 28.3 |
Secondary
Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24
The SF-36 Health Survey uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A positive change score indicates an improvement in HRQoL.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24 | Physical Component | 7.2 Units on a scale | Standard Deviation 8 |
| Tocilizumab 162 mg sc | Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24 | Mental Component | 6.1 Units on a scale | Standard Deviation 10.8 |
| Placebo sc | Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24 | Physical Component | 4.3 Units on a scale | Standard Deviation 5.9 |
| Placebo sc | Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24 | Mental Component | 3.0 Units on a scale | Standard Deviation 9.7 |
Secondary
Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24
The degree of joint damage was assessed using the van der Heijde modified total Sharp score (mTSS). The methodology quantifies the extent of bone erosions for 44 joints and joint space narrowing (JSN) for 42 joints, with higher scores representing greater damage. The independent read of X-ray images was performed by 2 primary readers. In case of discrepancy between the 2 primary readers, an adjudicator was involved. The mTSS can range from 0 to 448 with a higher score indicating more joint damage. A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tocilizumab 162 mg sc | Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24 | 0.62 Units on a scale | Standard Deviation 2.692 |
| Placebo sc | Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24 | 1.23 Units on a scale | Standard Deviation 2.816 |
Secondary
Percentage of Patients With ACR50 and ACR70 Responses at Week 24
A patient had an ACR50 response if there was at least a 50% improvement in the ACR scores. A patient had an ACR70 response if there was at least a 70% improvement in the ACR scores.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 162 mg sc | Percentage of Patients With ACR50 and ACR70 Responses at Week 24 | ACR50 | 39.8 Percentage of patients |
| Tocilizumab 162 mg sc | Percentage of Patients With ACR50 and ACR70 Responses at Week 24 | ACR70 | 19.7 Percentage of patients |
| Placebo sc | Percentage of Patients With ACR50 and ACR70 Responses at Week 24 | ACR50 | 12.3 Percentage of patients |
| Placebo sc | Percentage of Patients With ACR50 and ACR70 Responses at Week 24 | ACR70 | 5.0 Percentage of patients |
Secondary
Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.
Time frame: Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab 162 mg sc | Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24 | 32.0 Percentage of patients |
| Placebo sc | Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24 | 4.0 Percentage of patients |
Secondary
Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab 162 mg sc | Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24 | 45.2 Percentage of patients |
| Placebo sc | Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24 | 15.3 Percentage of patients |
Secondary
Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24
The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab 162 mg sc | Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24 | 58.0 Percentage of patients |
| Placebo sc | Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24 | 46.8 Percentage of patients |
Secondary
Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24
Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score \> 3.2 to ≤ 5.1, a change from baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score \> 5.1, a change from baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores \> 3.2.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab 162 mg sc | Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | Good Response | 41.7 Percentage of patients |
| Tocilizumab 162 mg sc | Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | Moderate Response | 44.9 Percentage of patients |
| Tocilizumab 162 mg sc | Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | No Response | 13.4 Percentage of patients |
| Placebo sc | Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | Moderate Response | 54.3 Percentage of patients |
| Placebo sc | Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | No Response | 31.9 Percentage of patients |
| Placebo sc | Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | Good Response | 13.8 Percentage of patients |
Secondary
Time to Onset of ACR20, ACR50, and ACR70 Responses
Time to first ACR response was calculated as the number of days between the date of the first ACR response minus the date of the first dose of study drug. Median days are reported.
Time frame: Baseline to Week 24
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tocilizumab 162 mg sc | Time to Onset of ACR20, ACR50, and ACR70 Responses | ACR50 | 115 Days |
| Tocilizumab 162 mg sc | Time to Onset of ACR20, ACR50, and ACR70 Responses | ACR70 | 174 Days |
| Tocilizumab 162 mg sc | Time to Onset of ACR20, ACR50, and ACR70 Responses | ACR20 | 57 Days |
| Placebo sc | Time to Onset of ACR20, ACR50, and ACR70 Responses | ACR50 | NA Days |
| Placebo sc | Time to Onset of ACR20, ACR50, and ACR70 Responses | ACR70 | NA Days |
| Placebo sc | Time to Onset of ACR20, ACR50, and ACR70 Responses | ACR20 | 86 Days |