Rheumatoid Arthritis
Conditions
Brief summary
This open-label, single arm study will investigate the safety, tolerability and efficacy of tocilizumab monotherapy, or combination therapy with non-biologic disease modifying antirheumatic drugs (DMARDs), in patients with severe active RA. Patients will receive tocilizumab 8mg/kg iv as a 60 minute infusion every 4 weeks for a total of 6 infusions. The anticipated time on study treatment is 3-12 months, and the target sample size is \>500 individuals.
Interventions
DRUGtocilizumab [RoActemra/Actemra]
8mg/kg iv (60 minute infusion)
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
* male and non-pregnant or nursing female patients \>=18 years of age; * body weight \<=150kg; * moderate to severe active RA (DAS28 \>=3.2) of \>=6 months duration; * on \>=1 non-biologic DMARDs at a stable dose for a period of \>= 8 weeks prior to start of treatment; * inadequate clinical response to a stable dose of non-biologic DMARD or anti-TNF therapy; * if receiving oral corticosteroids, the dose must have been stable for at least 25 of 28 days prior to start of treatment.
Exclusion criteria
* major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment; * rheumatic autoimmune disease other than RA; * prior history of, or current inflammatory joint disease other than RA; * functional class IV as defined by the ACR Classification of Functional Status in RA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs): Overall Summary | Weeks 4, 8, 12, 16, 20, and 24 | Percentage of participants with AEs, serious AEs (SAEs), related AEs, related SAEs, severe AEs, with AEs leading to withdrawal or dose modification, with infection, serious infection, infusion reactions, infusion reactions during an infusion, infusion reactions within 24 hours of an infusion, major adverse cardiac event (MACE), or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Low Disease Activity or Remission Based on DAS28 - Number of Participants With an Event | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity was defined as DAS28 ≤3.2 and remission was defined as DAS28 \<2.6. |
| Time to Low Disease Activity and Remission Based on DAS28 Score - Time to Event | Baseline,Weeks 4, 8, 12, 16, 20, and 24 | The time to low disease activity or remission was calculated as the number of days from study Day 1 to the first occurrence of low disease activity or remission. Participants who did not achieve low disease activity on or before Week 24 or who withdrew from the study prior to achieving low disease activity were considered censored. DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity defined as DAS28 ≤3.2 and remission defined as DAS28 \<2.6. |
| Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Weeks 4, 8, 12, 16, 20, and 24 | DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1. If the EULAR response could not be determined, it was set to 'No response'. |
| DAS28 Scores by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. A negative change from baseline indicates improvement. |
| Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Weeks 4, 8, 12, 16, 20, and 24 | ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (visual analog scale \[VAS\]); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI); or acute phase reactant (ESR or C-reactive protein \[CRP\]). Participants who did not have the required data to assess ACR status at a given visit were classified as non-responders. |
| Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response - Number of Participants With an Event | Weeks 4, 8, 12, 16, 20, and 24 | ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the HAQ-DI; or acute phase reactant (ESR or CRP). |
| Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response | Weeks 4, 8, 12, 16, 20, and 24 | ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the HAQ-DI; or acute phase reactant (ESR or CRP). Time to ACR response was calculated as the number of days from day 1 of study to the date of first achievement of ACR response. Data represent median time for responders only. |
| Swollen Joint Count by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 66. A negative change from baseline indicates improvement. |
| Tender Joint Count by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 68. A negative change from baseline indicates improvement. |
| Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity was defined as DAS28 less than or equal to (≤)3.2 and remission was defined as DAS28 less than (\<)2.6. |
| Physician's Global Assessment of Disease Activity by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 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=0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme=100 mm as maximum disease activity (maximum arthritis disease activity). The physician marked the line and the distance from the left edge was recorded. A negative change from baseline indicated improvement. |
| Patient's Global Assessment of Pain by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The participants assessed their pain using a 0 to 100 mm horizontal VAS. The left-hand extreme of the line=0 mm, and is described as no pain and the right-hand extreme=100 mm as unbearable pain. The participant marked the line and the distance from the left edge was recorded. A negative change from baseline indicated improvement. |
| C-Reactive Protein by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The test for CRP (mg per deciliter \[mg/dL\]) is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. |
| Erythrocyte Sedimentation Rate by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | ESR (mm/hr) is a blood test used to monitor therapy in inflammatory diseases such as rheumatoid arthritis (RA) and reflects acute phase reactant levels. Active disease in RA is defined by an ESR greater than 30 mm/hr. Change from baseline is computed as the value at each week minus the baseline value. A negative value in change from baseline indicates an improvement. |
| HAQ-DI Scores by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. |
| Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of \>3 points were considered clinically meaningful. |
| Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The HAQ-DI scale ranges from 0 to 3, where higher scores represent higher disease activity. A score of \<0.5 represents clinical remission. A participant achieves a clinically meaningful improvement in HAQ-DI if they had a reduction from baseline of ≥0.22. |
| Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | FACIT-Fatigue is a 13-item questionnaire; participants 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 participant's fatigue. 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 the participant's health status. |
| Patient's Global Assessment of Disease Activity by Visit | Baseline, Weeks 4, 8, 12, 16, 20, and 24 | The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line=0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme=100 mm, as maximum disease activity (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded. A negative change from baseline indicated improvement. |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, India, Ireland, Italy, Luxembourg, Netherlands, Poland, Portugal, Romania, Saudi Arabia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab 8 mg/kg Participants received tocilizumab 8 mg/kg IV once every 4 weeks for 20 weeks (total of 6 infusions). | 1,681 |
| Total | 1,681 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative | 11 |
| Overall Study | Adverse Event | 76 |
| Overall Study | Death | 4 |
| Overall Study | Lack of Efficacy | 46 |
| Overall Study | Lost to Follow-up | 10 |
| Overall Study | Physician Decision | 20 |
| Overall Study | Protocol Violation | 15 |
| Overall Study | Withdrawal by Subject | 33 |
Baseline characteristics
| Characteristic | Tocilizumab 8 mg/kg |
|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 12.34 |
| Sex: Female, Male Female | 1356 Participants |
| Sex: Female, Male Male | 325 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 370 / 1,681 |
| serious Total, serious adverse events | 131 / 1,681 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs): Overall Summary
Percentage of participants with AEs, serious AEs (SAEs), related AEs, related SAEs, severe AEs, with AEs leading to withdrawal or dose modification, with infection, serious infection, infusion reactions, infusion reactions during an infusion, infusion reactions within 24 hours of an infusion, major adverse cardiac event (MACE), or death.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: Safety population: all participants included in the study who received at least 1 dose of study medication and who had at least 1 postbaseline assessment of safety (post-baseline laboratory data, vital signs, or adverse events). number (n) equals (=) number of participants analyzed for the parameter within the specific population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Any AE | 77.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Related AE | 58.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Severe AE | 7.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | SAE | 7.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Related SAE | 3.5 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | AE leading to withdrawal | 5.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | AE leading to dose modification | 10.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Infection | 35.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Serious infection | 2.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Any infusion reaction (during or within 24 hours) | 17.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Infusion reaction during infusion | 6.7 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Infusion reaction within 24 hours of infusion | 12.6 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | MACE | 0.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Adverse Events (AEs): Overall Summary | Death | 0.2 percentage of participants |
Secondary
C-Reactive Protein by Visit
The test for CRP (mg per deciliter \[mg/dL\]) is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | C-Reactive Protein by Visit | Baseline (n=1681) | 1.94 mg/dL | Standard Deviation 2.775 |
| Tocilizumab | C-Reactive Protein by Visit | Week 4 (n=1649) | 0.52 mg/dL | Standard Deviation 1.834 |
| Tocilizumab | C-Reactive Protein by Visit | Change at Week 4 (n=1649) | -1.40 mg/dL | Standard Deviation 2.243 |
| Tocilizumab | C-Reactive Protein by Visit | Week 8 (n=1613) | 0.36 mg/dL | Standard Deviation 1.372 |
| Tocilizumab | C-Reactive Protein by Visit | Change at Week 8 (n=1613) | -1.59 mg/dL | Standard Deviation 2.474 |
| Tocilizumab | C-Reactive Protein by Visit | Week 12 (n=1571) | 0.28 mg/dL | Standard Deviation 1.247 |
| Tocilizumab | C-Reactive Protein by Visit | Change at Week 12 (n=1571) | -1.63 mg/dL | Standard Deviation 2.532 |
| Tocilizumab | C-Reactive Protein by Visit | Week 16 (n=1525) | 0.23 mg/dL | Standard Deviation 0.798 |
| Tocilizumab | C-Reactive Protein by Visit | Change at Week 16 (n=1525) | -1.70 mg/dL | Standard Deviation 2.655 |
| Tocilizumab | C-Reactive Protein by Visit | Week 20 (n=1481) | 0.23 mg/dL | Standard Deviation 1.078 |
| Tocilizumab | C-Reactive Protein by Visit | Change at Week 20 (n=1481) | -1.68 mg/dL | Standard Deviation 2.573 |
| Tocilizumab | C-Reactive Protein by Visit | Week 24 (n=1448) | 0.19 mg/dL | Standard Deviation 0.802 |
| Tocilizumab | C-Reactive Protein by Visit | Change at Week 24 (n=1448) | -1.74 mg/dL | Standard Deviation 2.608 |
Secondary
DAS28 Scores by Visit
DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. A negative change from baseline indicates improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | DAS28 Scores by Visit | Baseline (n=1677) | 5.96 units on a scale | Standard Deviation 1.201 |
| Tocilizumab | DAS28 Scores by Visit | Week 4 (n=1635) | 4.12 units on a scale | Standard Deviation 1.451 |
| Tocilizumab | DAS28 Scores by Visit | Change at Week 4 (n=1631) | -1.84 units on a scale | Standard Deviation 1.165 |
| Tocilizumab | DAS28 Scores by Visit | Week 8 (n=1594) | 3.35 units on a scale | Standard Deviation 1.442 |
| Tocilizumab | DAS28 Scores by Visit | Change at Week 8 (n=1590) | -2.60 units on a scale | Standard Deviation 1.336 |
| Tocilizumab | DAS28 Scores by Visit | Week 12 (n=1556) | 3.03 units on a scale | Standard Deviation 1.431 |
| Tocilizumab | DAS28 Scores by Visit | Change at Week 12 (n=1552) | -2.92 units on a scale | Standard Deviation 1.429 |
| Tocilizumab | DAS28 Scores by Visit | Week 16 (n=1509) | 2.80 units on a scale | Standard Deviation 1.459 |
| Tocilizumab | DAS28 Scores by Visit | Change at Week 16 (n=1506) | -3.14 units on a scale | Standard Deviation 1.464 |
| Tocilizumab | DAS28 Scores by Visit | Week 20 (n=1467) | 2.63 units on a scale | Standard Deviation 1.428 |
| Tocilizumab | DAS28 Scores by Visit | Change at Week 20 (n=1463) | -3.14 units on a scale | Standard Deviation 1.488 |
| Tocilizumab | DAS28 Scores by Visit | Week 24 (n=1455) | 2.52 units on a scale | Standard Deviation 1.378 |
| Tocilizumab | DAS28 Scores by Visit | Change at Week 24 (n=1451) | -3.42 units on a scale | Standard Deviation 1.438 |
Secondary
Erythrocyte Sedimentation Rate by Visit
ESR (mm/hr) is a blood test used to monitor therapy in inflammatory diseases such as rheumatoid arthritis (RA) and reflects acute phase reactant levels. Active disease in RA is defined by an ESR greater than 30 mm/hr. Change from baseline is computed as the value at each week minus the baseline value. A negative value in change from baseline indicates an improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Baseline (n=1681) | 39.20 mm/hr | Standard Deviation 26.843 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Week 4 (n=1642) | 13.13 mm/hr | Standard Deviation 16.468 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Change at Week 4 (n=1642) | -26.07 mm/hr | Standard Deviation 21.863 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Week 8 (n=1603) | 10.26 mm/hr | Standard Deviation 14.935 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Change at Week 8 (n=1603) | -28.93 mm/hr | Standard Deviation 23.945 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Week 12 (n=1567) | 8.97 mm/hr | Standard Deviation 12.527 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Change at Week 12 (n=1567) | -30.02 mm/hr | Standard Deviation 24.543 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Week 16 (n=1520) | 8.39 mm/hr | Standard Deviation 12.23 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Change at Week 16 (n=1520) | -30.43 mm/hr | Standard Deviation 24.703 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Week 20 (n=1474) | 7.81 mm/hr | Standard Deviation 11.653 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Change at Week 20 (n=1474) | -31.01 mm/hr | Standard Deviation 24.648 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Week 24 (n=1463) | 7.90 mm/hr | Standard Deviation 11.485 |
| Tocilizumab | Erythrocyte Sedimentation Rate by Visit | Change at Week 24 (n=1463) | -31.01 mm/hr | Standard Deviation 24.796 |
Secondary
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit
FACIT-Fatigue is a 13-item questionnaire; participants 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 participant's fatigue. 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 the participant's health status.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Baseline (n=1674) | 25.91 units on a scale | Standard Deviation 11.262 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Week 4 (n=1647) | 30.95 units on a scale | Standard Deviation 11.133 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Change at Week 4 (n=1640) | 5.01 units on a scale | Standard Deviation 8.916 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Week 8 (n=1611) | 33.51 units on a scale | Standard Deviation 10.865 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Change at Week 8 (n=1605) | 7.50 units on a scale | Standard Deviation 10.036 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Week 12 (n=1573) | 34.98 units on a scale | Standard Deviation 11.069 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Change at Week 12 (n=1568) | 8.86 units on a scale | Standard Deviation 10.463 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Week 16 (n=1529) | 35.78 units on a scale | Standard Deviation 10.959 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Change at Week 16 (n=1524) | 9.68 units on a scale | Standard Deviation 10.89 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Week 20 (n=1488) | 36.45 units on a scale | Standard Deviation 10.848 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Change at Week 20 (n=1483) | 10.31 units on a scale | Standard Deviation 10.947 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Week 24 (n=1466) | 36.92 units on a scale | Standard Deviation 10.823 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score by Visit | Change at Week 24 (n=1461) | 10.76 units on a scale | Standard Deviation 10.934 |
Secondary
HAQ-DI Scores by Visit
HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | HAQ-DI Scores by Visit | Baseline (n=1673) | 1.49 units on a scale | Standard Deviation 0.637 |
| Tocilizumab | HAQ-DI Scores by Visit | Week 4 (n=1648) | 1.27 units on a scale | Standard Deviation 0.665 |
| Tocilizumab | HAQ-DI Scores by Visit | Change at Week 4 (n=1641) | -022 units on a scale | Standard Deviation 0.448 |
| Tocilizumab | HAQ-DI Scores by Visit | Week 8 (n=1607) | 1.12 units on a scale | Standard Deviation 0.677 |
| Tocilizumab | HAQ-DI Scores by Visit | Change at Week 8 (n=1600) | -0.37 units on a scale | Standard Deviation 0.511 |
| Tocilizumab | HAQ-DI Scores by Visit | Week 12 (n=1570) | 1.03 units on a scale | Standard Deviation 0.684 |
| Tocilizumab | HAQ-DI Scores by Visit | Change at Week 12 (n=1562) | -0.46 units on a scale | Standard Deviation 0.553 |
| Tocilizumab | HAQ-DI Scores by Visit | Week 16 (n=1524) | 0.99 units on a scale | Standard Deviation 0.69 |
| Tocilizumab | HAQ-DI Scores by Visit | Change at Week 16 (n=1517) | -0.50 units on a scale | Standard Deviation 0.566 |
| Tocilizumab | HAQ-DI Scores by Visit | Week 20 (n=1483) | 0.95 units on a scale | Standard Deviation 0.687 |
| Tocilizumab | HAQ-DI Scores by Visit | Change at Week 20 (n=1476) | -0.53 units on a scale | Standard Deviation 0.573 |
| Tocilizumab | HAQ-DI Scores by Visit | Week 24 (n=1459) | 0.92 units on a scale | Standard Deviation 0.697 |
| Tocilizumab | HAQ-DI Scores by Visit | Change at Week 24 (n=1451) | -0.57 units on a scale | Standard Deviation 0.585 |
Secondary
Patient's Global Assessment of Disease Activity by Visit
The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line=0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme=100 mm, as maximum disease activity (maximum arthritis disease activity). The line was marked by the participant and the distance from the left edge was recorded. A negative change from baseline indicated improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Baseline (n=1677) | 62.52 mm | Standard Deviation 21.192 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Week 4 (n=1653) | 47.20 mm | Standard Deviation 23.945 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Change at Week 4 (n=1649) | -15.32 mm | Standard Deviation 23.852 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Week 8 (n=1610) | 37.95 mm | Standard Deviation 24.377 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Change at Week 8 (n=1606) | -24.52 mm | Standard Deviation 25.972 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Week 12 (n=1569) | 33.27 mm | Standard Deviation 23.474 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Change at Week 12 (n=1565) | -28.98 mm | Standard Deviation 25.885 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Week 16 (n=1525) | 30.92 mm | Standard Deviation 23.72 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Change at Week 16 (n=1522) | -31.42 mm | Standard Deviation 26.213 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Week 20 (n=1488) | 28.74 mm | Standard Deviation 22.948 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Change at Week 20 (n=1484) | -33.42 mm | Standard Deviation 26.16 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Week 24 (n=1472) | 26.68 mm | Standard Deviation 22.07 |
| Tocilizumab | Patient's Global Assessment of Disease Activity by Visit | Change at Week 24 (n=1468) | -35.53 mm | Standard Deviation 25.558 |
Secondary
Patient's Global Assessment of Pain by Visit
The participants assessed their pain using a 0 to 100 mm horizontal VAS. The left-hand extreme of the line=0 mm, and is described as no pain and the right-hand extreme=100 mm as unbearable pain. The participant marked the line and the distance from the left edge was recorded. A negative change from baseline indicated improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Baseline (n=1675) | 57.51 mm | Standard Deviation 22.582 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Week 4 (n=1654) | 43.10 mm | Standard Deviation 23.563 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Change at Week 4 (n=1648) | -14.41 mm | Standard Deviation 23.441 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Week 8 (n=1612) | 34.93 mm | Standard Deviation 23.711 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Change at Week 8 (n=1606) | -22.51 mm | Standard Deviation 25.138 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Week 12 (n=1572) | 31.02 mm | Standard Deviation 23.342 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Change at Week 12 (n=1566) | -26.21 mm | Standard Deviation 26.036 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Week 16 (n=1525) | 28.56 mm | Standard Deviation 23.016 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Change at Week 16 (n=1521) | -28.59 mm | Standard Deviation 26.079 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Week 20 (n=1489) | 26.76 mm | Standard Deviation 22.456 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Change at Week 20 (n=1483) | -30.29 mm | Standard Deviation 26.417 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Week 24 (n=1473) | 24.90 mm | Standard Deviation 21.398 |
| Tocilizumab | Patient's Global Assessment of Pain by Visit | Change at Week 24 (n=1468) | -32.13 mm | Standard Deviation 25.925 |
Secondary
Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit
ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (visual analog scale \[VAS\]); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI); or acute phase reactant (ESR or C-reactive protein \[CRP\]). Participants who did not have the required data to assess ACR status at a given visit were classified as non-responders.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 4, ACR20 | 36.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 4, ACR50 | 10.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 4, ACR70 | 2.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 4, ACR90 | 0.3 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 8, ACR20 | 55.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 8, ACR50 | 26.9 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 8, ACR70 | 10.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 8, ACR90 | 2.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 12, ACR20 | 61.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 12, ACR50 | 36.3 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 12, ACR70 | 17.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 12, ACR90 | 4.8 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 16, ACR20 | 64.1 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 16, ACR50 | 40.2 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 16, ACR70 | 21.1 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 16, ACR90 | 5.8 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 20, ACR20 | 65.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 20, ACR50 | 44.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 20, ACR70 | 22.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 20, ACR90 | 6.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 24, ACR20 | 66.9 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 24, ACR50 | 46.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 24, ACR70 | 26.4 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving an American College of Rheumatology 20 Percent (%), 50%, 70%, or 90% Improvement (ACR20/ACR50/ACR70/ACR90) by Visit | Week 24, ACR90 | 8.7 percentage of participants |
Secondary
Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit
DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1. If the EULAR response could not be determined, it was set to 'No response'.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 4, Good Response | 24.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 4, Moderate Response | 52.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 4, No Response | 22.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 8, Good Response | 44.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 8, Moderate Response | 40.8 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 8, No Response | 14.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 12, Good Response | 51.3 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 12, Moderate Response | 34.9 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 12, No Response | 13.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 16, Good Response | 57.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 16, Moderate Response | 27.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 16, No Response | 15.5 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 20, Good Response | 59.3 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 20, Moderate Response | 23.7 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 20, No Response | 17.0 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 24, Good Response | 59.6 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 24, Moderate Response | 23.8 percentage of participants |
| Tocilizumab | Percentage of Participants Achieving a Response by European League Against Rheumatism (EULAR) Response Category and Visit | Week 24, No Response | 16.6 percentage of participants |
Secondary
Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit
DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity was defined as DAS28 less than or equal to (≤)3.2 and remission was defined as DAS28 less than (\<)2.6.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; no imputation of missing data was performed for this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Baseline, low disease activity (n=1677) | 1.1 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Baseline, DAS28 <2.6 (n=1677) | 0.2 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 4, low disease activity (n=1635) | 27.6 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 4, DAS28 <2.6 (n=1635) | 14.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 8, low disease activity (n=1594) | 49.2 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 8, DAS28 <2.6 (n=1594) | 32.6 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 12, low disease activity (n=1556) | 57.3 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 12, DAS28 <2.6 (n=1556) | 40.0 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 16, low disease activity (n=1509) | 64.7 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 16, DAS28 <2.6 (n=1509) | 48.4 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 20, low disease activity (n=1467) | 69.3 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 20, DAS28 <2.6 (n=1467) | 54.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 24, low disease activity (n=1455) | 69.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved Low Disease Activity or Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) by Visit | Week 24, DAS28 <2.6 (n=1455) | 56.8 percentage of participants |
Secondary
Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit
The HAQ-DI scale ranges from 0 to 3, where higher scores represent higher disease activity. A score of \<0.5 represents clinical remission. A participant achieves a clinically meaningful improvement in HAQ-DI if they had a reduction from baseline of ≥0.22.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Baseline, Remission (n=1673) | 5.9 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 4, Remission (n=1648) | 12.6 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 4, Clinically meaningful improvement (n=1641) | 47.7 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 8, Remission (n=1607) | 19.0 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 8, Clinically meaningful improvement (n=1600) | 60.4 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 12, Remission (n=1570) | 23.9 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 12 Clinically meaningful improvement (n=1562) | 65.7 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 16, Remission (n=1524) | 26.4 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 16 Clinically meaningful improvement (n=1517) | 68.7 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 20, Remission (n=1483) | 28.1 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 20 Clinically meaningful improvement (n=1476) | 70.6 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 24, Remission (n=1459) | 31.5 percentage of participants |
| Tocilizumab | Percentage of Participants With HAQ-DI Clinical Remission and Clinically Meaningful Improvement By Visit | Week 24, Clinically meaningful improvement(n=1451) | 72.7 percentage of participants |
Secondary
Physician's Global Assessment of Disease Activity by Visit
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=0 mm, and is described as no disease activity (symptom-free and no arthritis symptoms) and the right-hand extreme=100 mm as maximum disease activity (maximum arthritis disease activity). The physician marked the line and the distance from the left edge was recorded. A negative change from baseline indicated improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Baseline (n=1675) | 58.82 mm | Standard Deviation 17.886 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Week 4 (n=1645) | 39.79 mm | Standard Deviation 19.858 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Change at Week 4 (n=1640) | -18.93 mm | Standard Deviation 20.126 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Week 8 (n=1605) | 30.01 mm | Standard Deviation 18.671 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Change at Week 8 (n=1601) | -28.65 mm | Standard Deviation 21.19 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Week 12 (n=1567) | 25.71 mm | Standard Deviation 18.217 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Change at Week 12 (n=1563) | -32.72 mm | Standard Deviation 21.295 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Week 16 (n=1525) | 23.17 mm | Standard Deviation 17.646 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Change at Week 16 (n=1521) | -35.49 mm | Standard Deviation 21.636 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Week 20 (n=1482) | 21.18 mm | Standard Deviation 17.064 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Change at Week 20 (n=1478) | -37.33 mm | Standard Deviation 21.855 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Week 24 (n=1459) | 19.53 mm | Standard Deviation 17.183 |
| Tocilizumab | Physician's Global Assessment of Disease Activity by Visit | Change at Week 24 (n=1455) | -39.10 mm | Standard Deviation 21.984 |
Secondary
Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit
The SF-36 covers 8 health dimensions including 4 physical subscales (physical function, role-physical, bodily pain, and general health) and 4 mental subscales (vitality, social function, role-emotional, and mental health). The scores range from a minimum of 0 to a maximum of 100, with a higher score indicating better quality of life. Improvements of \>3 points were considered clinically meaningful.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Baseline (n=1671) | 31.39 units on a scale | Standard Deviation 9.813 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Week 4 (n=1647) | 34.17 units on a scale | Standard Deviation 10.398 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Change at Week 4 (1639) | 2.79 units on a scale | Standard Deviation 8.064 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Week 8 (n=1608) | 36.39 units on a scale | Standard Deviation 10.829 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Change at Week 8 (n=1598) | 4.95 units on a scale | Standard Deviation 9.088 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Week 12 (n=1573) | 37.69 units on a scale | Standard Deviation 11.096 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Change at Week 12 (n=1564) | 6.19 units on a scale | Standard Deviation 9.751 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Week 16 (n=1529) | 38.41 units on a scale | Standard Deviation 11.139 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Change at Week 16 (n=1521) | 6.89 units on a scale | Standard Deviation 9.85 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Week 20 (n=1487) | 39.21 units on a scale | Standard Deviation 11.123 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Change at Week 20 (n=1479) | 7.66 units on a scale | Standard Deviation 10.306 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Week 24 (n=1465) | 39.52 units on a scale | Standard Deviation 11.302 |
| Tocilizumab | Short Form-36 (SF-36) Physical Functioning Domain Scores by Visit | Change at Week 24 (n=1457) | 7.92 units on a scale | Standard Deviation 10.211 |
Secondary
Swollen Joint Count by Visit
Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 66. A negative change from baseline indicates improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; missing data were handled using the LOCF approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Swollen Joint Count by Visit | Baseline | 12.76 swollen joints | Standard Deviation 9.183 |
| Tocilizumab | Swollen Joint Count by Visit | Week 4 | 9.24 swollen joints | Standard Deviation 10.371 |
| Tocilizumab | Swollen Joint Count by Visit | Change at Week 4 | -3.52 swollen joints | Standard Deviation 10.882 |
| Tocilizumab | Swollen Joint Count by Visit | Week 8 | 6.56 swollen joints | Standard Deviation 8.799 |
| Tocilizumab | Swollen Joint Count by Visit | Change at Week 8 | -6.20 swollen joints | Standard Deviation 10.597 |
| Tocilizumab | Swollen Joint Count by Visit | Week 12 | 5.62 swollen joints | Standard Deviation 8.324 |
| Tocilizumab | Swollen Joint Count by Visit | Change at Week 12 | -7.14 swollen joints | Standard Deviation 10.737 |
| Tocilizumab | Swollen Joint Count by Visit | Week 16 | 5.24 swollen joints | Standard Deviation 8.441 |
| Tocilizumab | Swollen Joint Count by Visit | Change at Week 16 | -7.52 swollen joints | Standard Deviation 11.114 |
| Tocilizumab | Swollen Joint Count by Visit | Week 20 | 4.77 swollen joints | Standard Deviation 8.15 |
| Tocilizumab | Swollen Joint Count by Visit | Change at Week 20 | -7.99 swollen joints | Standard Deviation 11.13 |
| Tocilizumab | Swollen Joint Count by Visit | Week 24 | 4.60 swollen joints | Standard Deviation 8.216 |
| Tocilizumab | Swollen Joint Count by Visit | Change at Week 24 | -8.16 swollen joints | Standard Deviation 11.179 |
Secondary
Tender Joint Count by Visit
Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 68. A negative change from baseline indicates improvement.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; missing data were handled using the last observation carried forward (LOCF) approach.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Tender Joint Count by Visit | Baseline | 22.82 tender joints | Standard Deviation 15.019 |
| Tocilizumab | Tender Joint Count by Visit | Week 4 | 16.55 tender joints | Standard Deviation 15.024 |
| Tocilizumab | Tender Joint Count by Visit | Change at Week 4 | -6.27 tender joints | Standard Deviation 13.384 |
| Tocilizumab | Tender Joint Count by Visit | Week 8 | 12.21 tender joints | Standard Deviation 13.227 |
| Tocilizumab | Tender Joint Count by Visit | Change at Week 8 | -10.61 tender joints | Standard Deviation 13.96 |
| Tocilizumab | Tender Joint Count by Visit | Week 12 | 10.47 tender joints | Standard Deviation 12.831 |
| Tocilizumab | Tender Joint Count by Visit | Change at Week 12 | -12.35 tender joints | Standard Deviation 14.611 |
| Tocilizumab | Tender Joint Count by Visit | Week 16 | 9.75 tender joints | Standard Deviation 12.372 |
| Tocilizumab | Tender Joint Count by Visit | Change at Week 16 | -13.06 tender joints | Standard Deviation 14.876 |
| Tocilizumab | Tender Joint Count by Visit | Week 20 | 9.31 tender joints | Standard Deviation 12.326 |
| Tocilizumab | Tender Joint Count by Visit | Change at Week 20 | -13.51 tender joints | Standard Deviation 15.312 |
| Tocilizumab | Tender Joint Count by Visit | Week 24 | 8.74 tender joints | Standard Deviation 12.115 |
| Tocilizumab | Tender Joint Count by Visit | Change at Week 24 | -14.08 tender joints | Standard Deviation 15.52 |
Secondary
Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response
ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the HAQ-DI; or acute phase reactant (ESR or CRP). Time to ACR response was calculated as the number of days from day 1 of study to the date of first achievement of ACR response. Data represent median time for responders only.
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; only participants with a response (ACR20/ACR50/ACR70/ACR90) were included in the analysis. n=number of participants with a response for the specified parameter
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response | ACR20 (n=1431) | 57.0 days |
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response | ACR50 (n=1075) | 84.0 days |
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response | ACR70 (n=659) | 90.0 days |
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response | ACR90 (n=232) | 113.0 days |
Secondary
Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response - Number of Participants With an Event
ACR20, ACR50, ACR70, and ACR90 are defined as ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in: swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) and ≥20%, ≥50%, ≥70%, or ≥90% improvement, respectively, in 3 of following 5 assessments: Patient's Global Assessment of Pain (VAS); Patient's Global Assessment of Disease Activity (VAS); Investigator/Physician's Global Assessment of Disease Activity (VAS); participant's assessment of disability measured by the HAQ-DI; or acute phase reactant (ESR or CRP).
Time frame: Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response - Number of Participants With an Event | ACR20 | 1431 participants |
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response - Number of Participants With an Event | ACR50 | 1075 participants |
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response - Number of Participants With an Event | ACR70 | 659 participants |
| Tocilizumab | Time to Achieve ACR20, ACR50, ACR70 and ACR90 Response - Number of Participants With an Event | ACR90 | 232 participants |
Secondary
Time to Low Disease Activity and Remission Based on DAS28 Score - Time to Event
The time to low disease activity or remission was calculated as the number of days from study Day 1 to the first occurrence of low disease activity or remission. Participants who did not achieve low disease activity on or before Week 24 or who withdrew from the study prior to achieving low disease activity were considered censored. DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity defined as DAS28 ≤3.2 and remission defined as DAS28 \<2.6.
Time frame: Baseline,Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population with DAS28 ≤3.2
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tocilizumab | Time to Low Disease Activity and Remission Based on DAS28 Score - Time to Event | Low disease activity (n=1320) | 63.0 days |
| Tocilizumab | Time to Low Disease Activity and Remission Based on DAS28 Score - Time to Event | Remission (n=1127) | 112.0 days |
Secondary
Time to Low Disease Activity or Remission Based on DAS28 - Number of Participants With an Event
DAS28 calculated from the number of swollen joints and tender joints using the 28 joints count, the ESR (mm/hr) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Low disease activity was defined as DAS28 ≤3.2 and remission was defined as DAS28 \<2.6.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Population: ITT population; Only population with complete DAS28 data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Time to Low Disease Activity or Remission Based on DAS28 - Number of Participants With an Event | Low disease activity | 1320 participants |
| Tocilizumab | Time to Low Disease Activity or Remission Based on DAS28 - Number of Participants With an Event | DAS28 <2.6 | 1127 participants |