Rheumatoid Arthritis
Conditions
Brief summary
This open-label, multi-center study in a local environment will evaluate the safety and the effect on disease activity with regard to reduction in signs and symptoms over 6 months of treatment in patients with moderate to severe active rheumatoid arthritis who experienced an inadequate response to a non-biologic DMARD. Tocilizumab 8 mg/kg will be administered as an intravenous infusion every 4 weeks for a total of 6 infusions as monotherapy or in combination with methotrexate (MTX). The anticipated time of study treatment is 24 weeks.
Interventions
DRUGtocilizumab [RoActemra]
tocilizumab 8 mg/kg intravenous infusion every 4 weeks for a total of 6 infusions
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 rheumatoid arthritis defined as DAS 28\>3.2 * Body weight \</=150 kg * Patient on at least 1 non-biologic DMARD on a stable dose for at least 8 weeks at any time prior to study start * Inadequate clinical response to a stable dose of a non-biologic DMARD
Exclusion criteria
* Major surgery within 8 weeks prior to screening or planned major surgery within 6 months following enrollment * Rheumatic autoimmune disease other than rheumatoid arthritis (RA) * Functional class IV as defined by the ACR classification * History or current inflammatory joint disease other than RA * Previous treatment with any cell depleting therapy * Previous treatment with methotrexate * Previous treatment with tocilizumab * Previous treatment with any biologic drug that is used in the treatment of RA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death | Baseline, every 4 weeks through Week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | DAS28 calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and participant's global assessment (PtGA) of disease activity by Visual analog Scale (VAS; participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤) 3.2 equals (=) low disease activity (LDA), DAS28 greater than (\>) 3.2 to 5.1 = moderate to high disease activity. A reduction of at least 1.2 units in DAS28 was considered clinically significant improvement. |
| Percentage of Participants Achieving LDA Assessed Using DAS28 | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than (\<) 3.2 = LDA. |
| Percentage of Participants Achieving Remission Assessed Using DAS28 | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Participants were considered in remission when reaching a DAS28 score \<2.6. |
| Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) C-reactive protein (CRP) at each visit. |
| Time To Achieve ACR20/ACR50/ACR70 | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via (HAQ, and 5) CRP at each visit. The median time to achieve ACR20/ACR50/ACR70 was calculated using Kaplan-Meier estimates. |
| SJC and TJC | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 28 joints were assessed for swelling and tenderness. Joints were classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) giving a total possible SJC and TJC score of 0 to 28 each. |
| Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | The participants assessed their pain using a 0 to 100 millimeter (mm) horizontal 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. The participants marked the line corresponding to their level of pain and the distance from the left edge was measured. |
| Assessment of Global Disease by the Participant Using VAS | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | The participant's global assessment of disease activity was assessed using a 0 to 100 mm horizontal 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). The participants marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured. |
| Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | The physician's global assessment of disease activity was assessed using 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). The physician marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured. |
| Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | Physical function was assessed using the HAQ. The HAQ scores range from 0 to 3 with, 0: no assistance needed, 1: participant uses a special device for day-to-day activities, 2: participant usually needs help from another person, and 3: participant uses BOTH a special device AND another person's help for day-to-day activities. |
| Mean C-Reactive Protein (CRP) Levels | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | CRP is an acute phase reactant and levels of CRP increase with inflammation. CRP is measured as milligrams per liter (mg/L). |
| Mean Erythrocyte Sedimentation Rate (ESR) Levels | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | ESR is an acute phase reactant and levels of ESR increase with inflammation. ESR is measured as mm/hour. |
| Percentage of Participants Experiencing Fatigue | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | — |
| Number of Participants Who Discontinued Tocilizumab | Week 52 | — |
Countries
Tunisia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants received tocilizumab 8 mg/kg intravenous infusion once every 4 weeks, for a total of 6 infusions during the initial phase of the study. Participants who completed the initial phase and had at least one moderate response according to the EULAR category entered the extension phase and received an additional 6 infusions of 8 mg/kg tocilizumab every 4 weeks. | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Phase | Lack of Efficacy | 1 |
| Extension Phase | Lost to Follow-up | 3 |
| Initial Phase | Adverse Event | 3 |
| Initial Phase | Pregnancy | 1 |
| Initial Phase | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 48.01 years STANDARD_DEVIATION 10.72 |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 51 |
| serious Total, serious adverse events | 3 / 51 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death
Time frame: Baseline, every 4 weeks through Week 52
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death | AEs | 78.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death | SAEs | 5.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death | Related AEs | 15.2 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death | Discontinuation due to AE | 7.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death | Death | 0 percentage of participants |
Secondary
Assessment of Global Disease by the Participant Using VAS
The participant's global assessment of disease activity was assessed using a 0 to 100 mm horizontal 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). The participants marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Baseline (n=51) | 64.7 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 4 (n=51) | 52.9 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 8 (n=48) | 40.9 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 12 (n=47) | 37.1 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 16 (n=48) | 34.4 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 20 (n=45) | 32.6 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 24 (n=46) | 29.3 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 36 (n=44) | 28.7 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 48 (n=41) | 20.1 mm |
| Tocilizumab | Assessment of Global Disease by the Participant Using VAS | Week 52 (n=41) | 24.1 mm |
Secondary
Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS)
The physician's global assessment of disease activity was assessed using 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). The physician marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Baseline (n=51) | 58.8 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 4 (n=51) | 45.9 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 8 (n=48) | 35.5 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 12 (n=47) | 31.1 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 16 (n=48) | 32.3 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 20 (n=45) | 28.9 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 24 (n=46) | 26.4 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 36 (n=44) | 23.5 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 48 (n=41) | 19.6 mm |
| Tocilizumab | Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | Week 52 (n=40) | 19.6 mm |
Secondary
Assessment of Pain by the Participant Using Visual Analog Scale (VAS)
The participants assessed their pain using a 0 to 100 millimeter (mm) horizontal 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. The participants marked the line corresponding to their level of pain and the distance from the left edge was measured.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Baseline (n=50) | 67.6 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 4 (n=48) | 49.4 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 8 (n=47) | 40.6 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 12 (n=47) | 36.0 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 16 (n=48) | 36.1 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 20 (n=45) | 33.2 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 24 (n=46) | 28.5 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 36 (n=44) | 30.0 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 48 (n=41) | 22.9 mm |
| Tocilizumab | Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | Week 52 (n=40) | 23.7 mm |
Secondary
Assessment of Physical Function Using Health Assessment Questionnaire (HAQ)
Physical function was assessed using the HAQ. The HAQ scores range from 0 to 3 with, 0: no assistance needed, 1: participant uses a special device for day-to-day activities, 2: participant usually needs help from another person, and 3: participant uses BOTH a special device AND another person's help for day-to-day activities.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Baseline (n=51) | 1.7 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 4 (n=50) | 1.2 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 8 (n=48) | 1.7 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 12 (n=47) | 0.9 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 16 (n=48) | 0.8 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 20 (n=46) | 0.8 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 24 (n=46) | 0.7 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 36 (n=40) | 1.0 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 48 (n=37) | 0.9 units on a scale |
| Tocilizumab | Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Week 52 (n=38) | 0.8 units on a scale |
Secondary
Mean C-Reactive Protein (CRP) Levels
CRP is an acute phase reactant and levels of CRP increase with inflammation. CRP is measured as milligrams per liter (mg/L).
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Baseline (n=51) | 26.6 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 4 (n=51) | 10.4 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 8 (n=49) | 9.5 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 12 (n=47) | 8.4 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 16 (n=46) | 9.1 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 20 (n=46) | 10.9 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 24 (n=44) | 11.0 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 36 (n=43) | 12.4 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 48 (n=42) | 10.4 mg/L |
| Tocilizumab | Mean C-Reactive Protein (CRP) Levels | Week 52 (n=40) | 7.4 mg/L |
Secondary
Mean Erythrocyte Sedimentation Rate (ESR) Levels
ESR is an acute phase reactant and levels of ESR increase with inflammation. ESR is measured as mm/hour.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Baseline (n=51) | 44.1 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 4 (n=51) | 21.0 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 8 (n=49) | 22.1 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 12 (n=47) | 17.0 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 16 (n=47) | 16.8 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 20 (n=46) | 13.5 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 24 (n=46) | 18.4 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 36 (n=43) | 15.6 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 48 (n=42) | 17.7 mm/hour |
| Tocilizumab | Mean Erythrocyte Sedimentation Rate (ESR) Levels | Week 52 (n=42) | 16.9 mm/hour |
Secondary
Number of Participants Who Discontinued Tocilizumab
Time frame: Week 52
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Number of Participants Who Discontinued Tocilizumab | 1 participants |
Secondary
Percentage of Participants Achieving LDA Assessed Using DAS28
DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than (\<) 3.2 = LDA.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants analyzed at a specific visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 4 (n=51) | 9.8 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 8 (n=49) | 26.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 12 (n=47) | 34.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 16 (n=47) | 36.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 20 (n=46) | 52.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 24 (n=46) | 47.8 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 36 (n=43) | 55.8 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 48 (n=41) | 65.9 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving LDA Assessed Using DAS28 | Week 52 (n=42) | 61.9 percentage of participants |
Secondary
Percentage of Participants Achieving Remission Assessed Using DAS28
DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Participants were considered in remission when reaching a DAS28 score \<2.6.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants analyzed at a specific visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Baseline (n=51) | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 4 (n=51) | 2.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 8 (n=49) | 12.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 12 (n=47) | 23.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 16 (n=47) | 23.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 20 (n=46) | 32.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 24 (n=46) | 41.3 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 36 (n=43) | 44.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 48 (n=41) | 41.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving Remission Assessed Using DAS28 | Week 52 (n=42) | 45.2 percentage of participants |
Secondary
Percentage of Participants Experiencing Fatigue
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24
Population: Safety population; n=number of participants analyzed for the given parameter at the specified visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Experiencing Fatigue | Baseline (n=50) | 22.0 percentage of participants |
| Tocilizumab | Percentage of Participants Experiencing Fatigue | Week 4 (n=49) | 16.3 percentage of participants |
| Tocilizumab | Percentage of Participants Experiencing Fatigue | Week 8 (n=48) | 4.2 percentage of participants |
| Tocilizumab | Percentage of Participants Experiencing Fatigue | Week 12 (n=45) | 13.3 percentage of participants |
| Tocilizumab | Percentage of Participants Experiencing Fatigue | Week 16 (n=47) | 10.6 percentage of participants |
| Tocilizumab | Percentage of Participants Experiencing Fatigue | Week 20 (n=44) | 11.4 percentage of participants |
| Tocilizumab | Percentage of Participants Experiencing Fatigue | Week 24 (n=46) | 10.9 percentage of participants |
Secondary
Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28)
DAS28 calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and participant's global assessment (PtGA) of disease activity by Visual analog Scale (VAS; participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤) 3.2 equals (=) low disease activity (LDA), DAS28 greater than (\>) 3.2 to 5.1 = moderate to high disease activity. A reduction of at least 1.2 units in DAS28 was considered clinically significant improvement.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; number (n)= number of participants analyzed at a specific visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 4 (n=51) | 56.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 8 (n=49) | 81.6 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 12 (n=47) | 83.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 16 (n=47) | 80.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 20 (n=46) | 95.7 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 24 (n=46) | 91.3 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 36 (n=43) | 86.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 48 (n=41) | 92.7 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | Week 52 (n=42) | 90.5 percentage of participants |
Secondary
Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70)
The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) C-reactive protein (CRP) at each visit.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 4 ACR20 | 29.2 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 4 ACR50 | 6.3 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 4 ACR70 | 0.0 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 8 ACR20 | 54.3 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 8 ACR50 | 21.7 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 8 ACR70 | 4.3 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 12 ACR20 | 61.2 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 12 ACR50 | 32.7 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 12 ACR70 | 12.2 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 16 ACR20 | 49.0 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 16 ACR50 | 24.5 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 16 ACR70 | 18.4 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 20 ACR20 | 70.8 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 20 ACR50 | 35.4 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 20 ACR70 | 12.5 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 24 ACR20 | 66.7 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 24 ACR50 | 33.3 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 24 ACR70 | 13.7 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 36 ACR20 | 54.2 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 36 ACR50 | 33.3 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 36 ACR70 | 14.6 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 48 ACR20 | 66.0 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 48 ACR50 | 48.9 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 48 ACR70 | 27.7 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 52 ACR20 | 58.3 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 52 ACR50 | 37.5 percentage of participants |
| Tocilizumab | Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | Week 52 ACR70 | 18.8 percentage of participants |
Secondary
SJC and TJC
28 joints were assessed for swelling and tenderness. Joints were classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) giving a total possible SJC and TJC score of 0 to 28 each.
Time frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population; n=number of participants assessed for the given parameter at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | SJC and TJC | Week 52 SJC (n=40) | 1.9 joints |
| Tocilizumab | SJC and TJC | Week 48 TJC (n=39) | 2.4 joints |
| Tocilizumab | SJC and TJC | Week 48 SJC (n=39) | 1.2 joints |
| Tocilizumab | SJC and TJC | Week 52 TJC (n=40) | 2.8 joints |
| Tocilizumab | SJC and TJC | Baseline TJC (n=51) | 14.3 joints |
| Tocilizumab | SJC and TJC | Baseline SJC (n=51) | 7.0 joints |
| Tocilizumab | SJC and TJC | Week 4 TJC (n=51) | 10.3 joints |
| Tocilizumab | SJC and TJC | Week 4 SJC (n=51) | 5.2 joints |
| Tocilizumab | SJC and TJC | Week 8 TJC (n=46) | 5.0 joints |
| Tocilizumab | SJC and TJC | Week 8 SJC (n=49) | 3.4 joints |
| Tocilizumab | SJC and TJC | Week 12 TJC (n=47) | 5.1 joints |
| Tocilizumab | SJC and TJC | Week 12 SJC (n=47) | 2.6 joints |
| Tocilizumab | SJC and TJC | Week 16 TJC (n=47) | 4.7 joints |
| Tocilizumab | SJC and TJC | Week 16 SJC (n=47) | 3.1 joints |
| Tocilizumab | SJC and TJC | Week 20 TJC (n=46) | 3.4 joints |
| Tocilizumab | SJC and TJC | Week 20 SJC (n=46) | 1.6 joints |
| Tocilizumab | SJC and TJC | Week 24 TJC (n=46) | 3.5 joints |
| Tocilizumab | SJC and TJC | Week 24 SJC (n=46) | 1.6 joints |
| Tocilizumab | SJC and TJC | Week 28 TJC (n=34) | 3.3 joints |
| Tocilizumab | SJC and TJC | Week 28 SJC (n=34) | 1.3 joints |
| Tocilizumab | SJC and TJC | Week 32 TJC (n=34) | 2.5 joints |
| Tocilizumab | SJC and TJC | Week 32 SJC (n=34) | 1.4 joints |
| Tocilizumab | SJC and TJC | Week 36 TJC (n=41) | 3.6 joints |
| Tocilizumab | SJC and TJC | Week 36 SJC (n=41) | 2.0 joints |
| Tocilizumab | SJC and TJC | Week 40 TJC (n=33) | 2.6 joints |
| Tocilizumab | SJC and TJC | Week 40 SJC (n=33) | 1.3 joints |
| Tocilizumab | SJC and TJC | Week 44 TJC (n=34) | 2.6 joints |
| Tocilizumab | SJC and TJC | Week 44 SJC (n=34) | 1.5 joints |
Secondary
Time To Achieve ACR20/ACR50/ACR70
The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via (HAQ, and 5) CRP at each visit. The median time to achieve ACR20/ACR50/ACR70 was calculated using Kaplan-Meier estimates.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52
Population: Safety population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tocilizumab | Time To Achieve ACR20/ACR50/ACR70 | ACR20 | 8.0 weeks |
| Tocilizumab | Time To Achieve ACR20/ACR50/ACR70 | ACR50 | 20.0 weeks |
| Tocilizumab | Time To Achieve ACR20/ACR50/ACR70 | ACR70 | NA weeks |