Rheumatoid Arthritis
Conditions
Brief summary
This Phase IIIb, multicenter, open label, single arm study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab as monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active rheumatoid arthritis who are either naïve to or have an inadequate response to prior non-biologic or/and biologic DMARDs. The anticipated time on study treatment is 52 weeks. Those participants who will complete the 60-week study period and have achieved Disease Activity Score 28 (DAS28) remission or a good European League Against Rheumatism (EULAR) response at 52 weeks will be eligible to enter the extension phase until tocilizumab is commercially available and reimbursed in Greece.
Interventions
DRUGAzathioprine
Participants may receive azathioprine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.
DRUGChloroquine
Participants may receive chloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.
DRUGHydroxychloroquine
Participants may receive hydroxychloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.
DRUGLeflunomide
Participants may receive leflunomide as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.
DRUGMethotrexate
Participants may receive methotrexate as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.
DRUGSulfasalazine
Participants may receive sulfasalazine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.
DRUGTocilizumab
Participants will receive tocilizumab at a fixed dose of 162 mg SC QW either as monotherapy or in combination with non-biologic DMARDs.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria * Oral corticosteroids (less than or equal to \[\</=\] 10 milligrams per day \[mg/day\] prednisolone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for greater than or equal to \[\>/=\] 4 weeks prior to baseline * Permitted non biologic DMARDs are allowed if a stable dose for at least 4 weeks prior to baseline * Receiving treatment on an outpatient basis, not including tocilizumab * Females of childbearing potential and males with female partners of childbearing potential must agree to use a reliable means of contraception during the study; females of childbearing potential must use a reliable means of contraception for at least 3 month following the last dose of tocilizumab
Exclusion criteria
* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline * Rheumatic autoimmune disease other than rheumatoid arthritis; secondary Sjögren's syndrome with rheumatoid arthritis is permitted * Functional Class 4 as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis * Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16 * Prior history of or current inflammatory joint disease other than rheumatoid arthritis * Participants with lack of peripheral venous access * Exposure to tocilizumab (either intravenous \[IV\] or SC) at any time prior to baseline * Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of screening * Previous treatment with any cell-depending therapies * Treatment with IV gamma globulin, plasmapheresis within 6 months of baseline * Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline * Immunization with a live/attenuated vaccine within 4 weeks prior to baseline * Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation * History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies * Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease * Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections * Any major episode of infection requiring hospitalization of treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening * Active tuberculosis (TB) requiring treatment within the previous 3 years * Positive for hepatitis B surface antigen or hepatitis C antibody * Primary or secondary immunodeficiency (history of or currently active) * Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years * Pregnant or breast feeding women * History of alcohol, drug or chemical abuse within 1 year prior to screening * Neuropathies or other conditions that interfere with pain evaluation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24 | Week 24 | DAS28-ESR score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), patient global assessment of disease activity (PGA) (general health \[GH\]) using visual analog scale (VAS): 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in millimeters per hour \[mm/hr\]). The score is calculated using the following formula: DAS28-ESR = \[0.56 multiplied by (\*) square root (√) of TJC28\] plus (+) \[0.28\*√SJC28\]+\[0.70\*the natural logarithm (ln) ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score of less than (\<) 2.6 represents DAS28-ESR remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Weeks 28, 32, 36, 40, 44, 48, 52 | DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = \[0.56 \* √TJC28 + \[0.28\*√SJC28\]+\[0.70\*ln ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score \<2.6 represents DAS28-ESR remission. DAS28-ESR score greater than or equal to (\>/=) 2.6 and \<3.2 represents LDA. |
| Change From Baseline in DAS28-ESR up to Week 52 | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = \[0.56 \* √TJC28 + \[0.28\*√SJC28\]+\[0.70\*ln ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. A negative change from baseline indicates an improvement. |
| Number of Participants With American College of Rheumatology 20 (ACR20) Response | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | ACR20 response was defined as \>/=20% improvement from baseline in both TJC28 and SJC28 as well as in 3 out of 5 additional parameters: Separate patient and physician's global assessment of disease activity on VAS (0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS), patient's assessment of pain on VAS (0 mm=no pain to 100 mm=unbearable pain, displayed on the 100 mm horizontal VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without any difficulty to 3=unable to do), and acute phase response (ESR in mm/hr, for a total possible score of 0 to 10). |
| Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Response to treatment was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the baseline visit. Participants with a score lesser than or equal to (\</=) 3.2 and reduction of greater than (\>) 1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score \</=5.1 with reduction of \>0.6 to \</=1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to \</=1.2 points, or any score with reduction \</=0.6 points, were assessed as having 'no response'. |
| Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | SDAI is an index for measuring disease activity. SDAI is the numerical sum of five outcome parameters: TJC28 and SJC28, PGA and physician global assessment of disease activity assessed on VAS (0 centimeter \[cm\]-10 cm); 0 cm= no disease activity and 10 cm= worst disease activity, and CRP (in milligrams per deciliter \[mg/dL\]). SDAI total score ranges from 0 to 86, with higher scores indicating increased (or severe) disease activity. SDAI score \</=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity. |
| Change From Baseline in TJC28 up to Week 52 | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | 28 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 28. A negative change from baseline indicated improvement. |
| Change From Baseline in SJC28 up to Week 52 | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | 28 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 28. A negative change from baseline indicated improvement. |
| Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation | From Baseline up to Week 52 | — |
| Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Weeks 24, 28, 32, 36, 40, 44, 48, 52 | DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = \[0.56 \* √TJC28 + \[0.28\*√SJC28\]+\[0.70\*ln ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score \<2.6 represents DAS28-ESR remission. The percentage reported for Week 24 is based on confirmation on switching to SC tocilizumab monotherapy. |
| Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60) | All samples were tested using a screening assay and, if positive, by a confirmation assay to determine specificity and a neutralizing assay to test for the ability to inhibit the activity of tocilizumab. Number of participants with a positive assay result for screening assay (ATA - Screen), confirmatory assay (ATA - Confirmatory), and neutralizing assay (ATA - Neutralizing) was reported separately. |
| Soluble Interleukin-6 Receptor (sIL-6R) Levels | Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60) | — |
| Tocilizumab Serum Levels | Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60) | — |
| PGA, Using VAS Score | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | PGA was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as no disease activity (symptom-free and no arthritis symptoms) and the extreme right end = 100 mm, and was described as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity). |
| Patient Assessment of Pain, Using VAS Score | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | The participant's level of pain was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as no pain and the extreme right end = 100 mm, and was described as unbearable pain. Higher values correspond to worst state of participant (higher level of pain). |
| HAQ-DI Score | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | The Stanford HAQ-DI is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Responses in each component set were scored from 0 (without any difficulty) to 3 (unable to do). The highest score recorded for any question in a category determines the score for the category, unless aids, devices, or help from another person was required. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3. Scores of 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 as moderate to severe disability, and 2 to 3 as severe to very severe disability. |
| Percentage of Participants Who Received All Planned Study Medication (Compliance) | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Compliance (in terms of percentage of participants who received all planned study medication) was assessed on the basis of participant diary cards and return records. |
| Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | FACIT-Fatigue total score is sum of FACIT-General subscale score and FACIT-Fatigue (additional concerns) subscale score. FACT-General consists of 27 questions grouped in 4 domains of general health-related quality of life: physical well-being, social/family well-being, emotional well-being, and functional well-being; each item ranges from 0 (not at all) to 4 (very much). FACT-General score ranges between 0-108. FACIT-Fatigue subscale is a 13-item questionnaire that evaluates self-reported fatigue and its impact upon daily activities. Each item ranges from 0 (Not at all) to 4 (Very much). For all items, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue subscale score for a total possible score of 0 (worse score) to 52 (better score). FACIT-Fatigue total score (FACT-G plus FACT-F subscale scores) ranges from 0 (better score) to 160 (worse score). |
| Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation | From Baseline up to Week 52 | Reasons for corticosteroid dose reduction included: Safety Reasons (including elevated liver function test results, respiratory infections, infections and infestations, gastrointestinal disorders etc.); Other Reasons (disease remission, improvement etc.); and Unknown Reasons (including no reason). Number of participants by reasons (Safety, Other, Unknown) for corticosteroid dose reduction or discontinuation were reported. |
Countries
Greece
Participant flow
Recruitment details
Participants were enrolled in 9 locations in Greece
Pre-assignment details
A total of 100 participants were enrolled, out of which 97 participants received treatment. Analyses were performed in 97 participants.
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Participants received tocilizumab 162 mg SC injection QW either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment was according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant might either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52. | 97 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Anaphylaxis or serious hypersensitivity | 2 |
| Overall Study | Insufficient therapeutic response | 13 |
| Overall Study | Lost to Follow-up | 10 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Tocilizumab |
|---|---|
| Age, Continuous | 56.27 years STANDARD_DEVIATION 12.77 |
| Sex: Female, Male Female | 86 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 31 | 38 / 66 |
| serious Total, serious adverse events | 2 / 31 | 5 / 66 |
Outcome results
Primary
Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24
DAS28-ESR score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), patient global assessment of disease activity (PGA) (general health \[GH\]) using visual analog scale (VAS): 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in millimeters per hour \[mm/hr\]). The score is calculated using the following formula: DAS28-ESR = \[0.56 multiplied by (\*) square root (√) of TJC28\] plus (+) \[0.28\*√SJC28\]+\[0.70\*the natural logarithm (ln) ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score of less than (\<) 2.6 represents DAS28-ESR remission.
Time frame: Week 24
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24 | 40 percentage of participants |
Secondary
Change From Baseline in DAS28-ESR up to Week 52
DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = \[0.56 \* √TJC28 + \[0.28\*√SJC28\]+\[0.70\*ln ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. A negative change from baseline indicates an improvement.
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 20 | -2.93 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 2 | -0.99 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 4 | -1.70 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 8 | -2.20 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 12 | -2.56 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 16 | -2.59 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 24 | -3.14 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 28 | -3.22 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 32 | -3.34 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 36 | -3.32 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 40 | -3.40 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 44 | -3.45 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 48 | -3.42 units on a scale |
| Tocilizumab | Change From Baseline in DAS28-ESR up to Week 52 | Change at Week 52 | -3.40 units on a scale |
Secondary
Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52
SDAI is an index for measuring disease activity. SDAI is the numerical sum of five outcome parameters: TJC28 and SJC28, PGA and physician global assessment of disease activity assessed on VAS (0 centimeter \[cm\]-10 cm); 0 cm= no disease activity and 10 cm= worst disease activity, and CRP (in milligrams per deciliter \[mg/dL\]). SDAI total score ranges from 0 to 86, with higher scores indicating increased (or severe) disease activity. SDAI score \</=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity.
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 2 | -3.41 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 4 | -6.54 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 8 | -8.72 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 12 | -11.07 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 16 | -13.47 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 20 | -13.88 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 24 | -14.08 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 28 | -15.37 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 32 | -16.09 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 36 | -15.61 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 40 | -14.86 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 44 | -16.31 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 48 | -16.47 units on a scale |
| Tocilizumab | Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52 | Change at Week 52 | -17.35 units on a scale |
Secondary
Change From Baseline in SJC28 up to Week 52
28 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 28. A negative change from baseline indicated improvement.
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 2 | -1.82 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 4 | -3.08 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 8 | -4.71 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 12 | -5.24 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 16 | -5.79 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 20 | -6.06 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 24 | -6.60 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 28 | -6.65 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 32 | -6.73 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 36 | -6.76 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 40 | -6.91 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 44 | -6.82 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 48 | -6.63 swollen joints |
| Tocilizumab | Change From Baseline in SJC28 up to Week 52 | Change at Week 52 | -6.98 swollen joints |
Secondary
Change From Baseline in TJC28 up to Week 52
28 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 28. A negative change from baseline indicated improvement.
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 2 | -1.30 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 4 | -3.26 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 8 | -4.97 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 12 | -5.82 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 16 | -6.39 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 20 | -7.03 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 24 | -7.72 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 28 | -7.91 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 32 | -8.38 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 36 | -8.28 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 40 | -8.22 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 44 | -8.63 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 48 | -8.26 tender joints |
| Tocilizumab | Change From Baseline in TJC28 up to Week 52 | Change at Week 52 | -8.75 tender joints |
Secondary
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score
FACIT-Fatigue total score is sum of FACIT-General subscale score and FACIT-Fatigue (additional concerns) subscale score. FACT-General consists of 27 questions grouped in 4 domains of general health-related quality of life: physical well-being, social/family well-being, emotional well-being, and functional well-being; each item ranges from 0 (not at all) to 4 (very much). FACT-General score ranges between 0-108. FACIT-Fatigue subscale is a 13-item questionnaire that evaluates self-reported fatigue and its impact upon daily activities. Each item ranges from 0 (Not at all) to 4 (Very much). For all items, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue subscale score for a total possible score of 0 (worse score) to 52 (better score). FACIT-Fatigue total score (FACT-G plus FACT-F subscale scores) ranges from 0 (better score) to 160 (worse score).
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 1 | 89.68 units on a scale | Standard Deviation 24.32 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 2 | 91.83 units on a scale | Standard Deviation 22.91 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 4 | 100.38 units on a scale | Standard Deviation 24.36 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 8 | 103.16 units on a scale | Standard Deviation 26.28 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 12 | 106.39 units on a scale | Standard Deviation 24.74 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 16 | 110.17 units on a scale | Standard Deviation 24.96 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 20 | 112.60 units on a scale | Standard Deviation 25.5 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 24 | 114.21 units on a scale | Standard Deviation 25.23 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 28 | 114.85 units on a scale | Standard Deviation 26.95 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 32 | 117.01 units on a scale | Standard Deviation 26 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 36 | 116.50 units on a scale | Standard Deviation 26.17 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 40 | 116.59 units on a scale | Standard Deviation 26.2 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 44 | 119.67 units on a scale | Standard Deviation 26.64 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 48 | 119.83 units on a scale | Standard Deviation 26.51 |
| Tocilizumab | Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score | Week 52 | 121.82 units on a scale | Standard Deviation 25.34 |
Secondary
HAQ-DI Score
The Stanford HAQ-DI is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Responses in each component set were scored from 0 (without any difficulty) to 3 (unable to do). The highest score recorded for any question in a category determines the score for the category, unless aids, devices, or help from another person was required. The HAQ-DI score was calculated as the sum of the category scores divided by the number of categories scored, giving a possible range of scores from 0 to 3. Scores of 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 as moderate to severe disability, and 2 to 3 as severe to very severe disability.
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | HAQ-DI Score | Week 1 | 1.31 units on a scale | Standard Deviation 0.66 |
| Tocilizumab | HAQ-DI Score | Week 2 | 1.22 units on a scale | Standard Deviation 0.64 |
| Tocilizumab | HAQ-DI Score | Week 4 | 1.09 units on a scale | Standard Deviation 0.66 |
| Tocilizumab | HAQ-DI Score | Week 8 | 0.91 units on a scale | Standard Deviation 0.66 |
| Tocilizumab | HAQ-DI Score | Week 12 | 0.82 units on a scale | Standard Deviation 0.58 |
| Tocilizumab | HAQ-DI Score | Week 16 | 0.72 units on a scale | Standard Deviation 0.59 |
| Tocilizumab | HAQ-DI Score | Week 20 | 0.68 units on a scale | Standard Deviation 0.56 |
| Tocilizumab | HAQ-DI Score | Week 24 | 0.66 units on a scale | Standard Deviation 0.55 |
| Tocilizumab | HAQ-DI Score | Week 28 | 0.66 units on a scale | Standard Deviation 0.57 |
| Tocilizumab | HAQ-DI Score | Week 32 | 0.59 units on a scale | Standard Deviation 0.58 |
| Tocilizumab | HAQ-DI Score | Week 36 | 0.63 units on a scale | Standard Deviation 0.58 |
| Tocilizumab | HAQ-DI Score | Week 40 | 0.60 units on a scale | Standard Deviation 0.59 |
| Tocilizumab | HAQ-DI Score | Week 44 | 0.59 units on a scale | Standard Deviation 0.61 |
| Tocilizumab | HAQ-DI Score | Week 48 | 0.56 units on a scale | Standard Deviation 0.59 |
| Tocilizumab | HAQ-DI Score | Week 52 | 0.54 units on a scale | Standard Deviation 0.6 |
Secondary
Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation
Reasons for corticosteroid dose reduction included: Safety Reasons (including elevated liver function test results, respiratory infections, infections and infestations, gastrointestinal disorders etc.); Other Reasons (disease remission, improvement etc.); and Unknown Reasons (including no reason). Number of participants by reasons (Safety, Other, Unknown) for corticosteroid dose reduction or discontinuation were reported.
Time frame: From Baseline up to Week 52
Population: Full analysis set. Overall number of participants analyzed = participants with corticosteroid dose reduction/discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation | Safety | 6 participants |
| Tocilizumab | Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation | Other | 10 participants |
| Tocilizumab | Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation | Unknown | 2 participants |
Secondary
Number of Participants With American College of Rheumatology 20 (ACR20) Response
ACR20 response was defined as \>/=20% improvement from baseline in both TJC28 and SJC28 as well as in 3 out of 5 additional parameters: Separate patient and physician's global assessment of disease activity on VAS (0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS), patient's assessment of pain on VAS (0 mm=no pain to 100 mm=unbearable pain, displayed on the 100 mm horizontal VAS), Health Assessment Questionnaire - Disability Index (HAQ-DI) (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without any difficulty to 3=unable to do), and acute phase response (ESR in mm/hr, for a total possible score of 0 to 10).
Time frame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 20 | 16 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 24 | 9 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 28 | 13 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 32 | 10 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 36 | 11 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 40 | 10 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 44 | 12 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 48 | 13 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 52 | 15 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 2 | 19 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 4 | 19 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 8 | 23 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 12 | 9 participants |
| Tocilizumab | Number of Participants With American College of Rheumatology 20 (ACR20) Response | Week 16 | 13 participants |
Secondary
Number of Participants With Anti-Tocilizumab Antibodies (ATA)
All samples were tested using a screening assay and, if positive, by a confirmation assay to determine specificity and a neutralizing assay to test for the ability to inhibit the activity of tocilizumab. Number of participants with a positive assay result for screening assay (ATA - Screen), confirmatory assay (ATA - Confirmatory), and neutralizing assay (ATA - Neutralizing) was reported separately.
Time frame: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 1: ATA - Screen | 7 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 1: ATA - Confirmatory | 4 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 1: ATA - Neutralizing | 0 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 12: ATA - Screen | 3 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 12: ATA - Confirmatory | 0 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 12: ATA - Neutralizing | 0 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 24: ATA - Screen | 3 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 24: ATA - Confirmatory | 1 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 24: ATA - Neutralizing | 1 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 36: ATA - Screen | 2 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 36: ATA - Confirmatory | 0 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 36: ATA - Neutralizing | 0 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 52: ATA - Screen | 2 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 52: ATA - Confirmatory | 0 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 52: ATA - Neutralizing | 0 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 60: ATA - Screen | 1 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 60: ATA - Confirmatory | 1 participants |
| Tocilizumab | Number of Participants With Anti-Tocilizumab Antibodies (ATA) | Week 60: ATA - Neutralizing | 0 participants |
Secondary
Patient Assessment of Pain, Using VAS Score
The participant's level of pain was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as no pain and the extreme right end = 100 mm, and was described as unbearable pain. Higher values correspond to worst state of participant (higher level of pain).
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 1 | 46.40 mm | Standard Deviation 27.43 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 2 | 52.04 mm | Standard Deviation 24.46 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 4 | 49.87 mm | Standard Deviation 23.35 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 8 | 42.72 mm | Standard Deviation 23.2 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 12 | 37.21 mm | Standard Deviation 21.29 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 16 | 34.24 mm | Standard Deviation 22.49 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 20 | 31.00 mm | Standard Deviation 19.42 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 24 | 29.57 mm | Standard Deviation 19.66 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 28 | 29.63 mm | Standard Deviation 19.07 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 32 | 25.50 mm | Standard Deviation 17.95 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 36 | 26.78 mm | Standard Deviation 22.13 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 40 | 27.50 mm | Standard Deviation 21.93 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 44 | 26.88 mm | Standard Deviation 19.96 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 48 | 23.61 mm | Standard Deviation 18.63 |
| Tocilizumab | Patient Assessment of Pain, Using VAS Score | Week 52 | 23.98 mm | Standard Deviation 20.19 |
Secondary
Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24
DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = \[0.56 \* √TJC28 + \[0.28\*√SJC28\]+\[0.70\*ln ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score \<2.6 represents DAS28-ESR remission. DAS28-ESR score greater than or equal to (\>/=) 2.6 and \<3.2 represents LDA.
Time frame: Weeks 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 28: Remission | 5.1 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 36: Remission | 4.1 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 40: Remission | 9.5 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 48: Remission | 8.5 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 32: Remission | 8.1 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 44: Remission | 6.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 52: Remission | 6 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 28: LDA | 7.6 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 32: LDA | 1.4 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 36: LDA | 6.8 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 40: LDA | 6.8 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 44: LDA | 6.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 48: LDA | 4.2 percentage of participants |
| Tocilizumab | Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24 | Week 52: LDA | 9 percentage of participants |
Secondary
Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24
DAS28-ESR score is a measure of participant's disease activity calculated using TJC28, SJC28, PGA using VAS 0 mm=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in mm/hr) for a total possible score of 0 to 10. The score is calculated using the following formula: DAS28-ESR = \[0.56 \* √TJC28 + \[0.28\*√SJC28\]+\[0.70\*ln ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score \<2.6 represents DAS28-ESR remission. The percentage reported for Week 24 is based on confirmation on switching to SC tocilizumab monotherapy.
Time frame: Weeks 24, 28, 32, 36, 40, 44, 48, 52
Population: Per protocol analysis. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 28 | 34.2 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 32 | 36.5 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 36 | 36.5 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 40 | 36.5 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 44 | 35.2 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 48 | 35.7 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 52 | 38.8 percentage of participants |
| Tocilizumab | Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24 | Week 24 | 38.7 percentage of participants |
Secondary
Percentage of Participants Who Received All Planned Study Medication (Compliance)
Compliance (in terms of percentage of participants who received all planned study medication) was assessed on the basis of participant diary cards and return records.
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 1 | 66 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 2 | 97.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 4 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 8 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 12 | 98.9 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 16 | 97.6 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 20 | 98.8 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 24 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 28 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 32 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 36 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 40 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 44 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 48 | 100 percentage of participants |
| Tocilizumab | Percentage of Participants Who Received All Planned Study Medication (Compliance) | Week 52 | 100 percentage of participants |
Secondary
Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation
Time frame: From Baseline up to Week 52
Population: Full analysis set. Overall number of participants analyzed = participants who used corticosteroids during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tocilizumab | Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation | 48.6 percentage of participants |
Secondary
Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria
Response to treatment was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the baseline visit. Participants with a score lesser than or equal to (\</=) 3.2 and reduction of greater than (\>) 1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score \</=5.1 with reduction of \>0.6 to \</=1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to \</=1.2 points, or any score with reduction \</=0.6 points, were assessed as having 'no response'.
Time frame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Overall number of participants analyzed = participants evaluable for this outcome measure. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 2: Good response | 9.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 2: Moderate response | 44.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 2: No response | 45.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 4: Good response | 9.5 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 4: Moderate response | 38.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 4: No response | 51.6 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 8: Good response | 10.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 8: Moderate response | 23.6 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 8: No response | 65.6 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 12: Good response | 9.2 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 12: Moderate response | 20.7 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 12: No response | 70.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 16: Good response | 5.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 16: Moderate response | 15.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 16: No response | 78.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 20: Good response | 6.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 20: Moderate response | 26.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 20: No response | 67.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 24: Good response | 6.2 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 24: Moderate response | 21.2 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 24: No response | 72.6 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 28: Good response | 6.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 28: Moderate response | 11.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 28: No response | 82.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 32: Good response | 0 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 32: Moderate response | 18.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 32: No response | 81.1 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 36: Good response | 1.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 36: Moderate response | 14.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 36: No response | 83.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 40: Good response | 5.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 40: Moderate response | 17.6 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 40: No response | 77 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 44: Good response | 2.8 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 44: Moderate response | 13.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 44: No response | 83.3 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 48: Good response | 5.7 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 48: Moderate response | 11.4 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 48: No response | 82.9 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 52: Good response | 94 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 52: Moderate response | 6 percentage of participants |
| Tocilizumab | Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria | Week 52: No response | 0 percentage of participants |
Secondary
PGA, Using VAS Score
PGA was assessed on a 0 to 100 mm horizontal VAS. The extreme left end of the line = 0 mm, and was described as no disease activity (symptom-free and no arthritis symptoms) and the extreme right end = 100 mm, and was described as maximum disease activity (maximum arthritis disease activity). Higher values correspond to worst state of participant (high disease activity).
Time frame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | PGA, Using VAS Score | Week 1 | 28.26 mm | Standard Deviation 20.25 |
| Tocilizumab | PGA, Using VAS Score | Week 2 | 27.57 mm | Standard Deviation 20.08 |
| Tocilizumab | PGA, Using VAS Score | Week 4 | 28.36 mm | Standard Deviation 19.37 |
| Tocilizumab | PGA, Using VAS Score | Week 8 | 32.28 mm | Standard Deviation 22.09 |
| Tocilizumab | PGA, Using VAS Score | Week 12 | 28.73 mm | Standard Deviation 23.01 |
| Tocilizumab | PGA, Using VAS Score | Week 16 | 24.40 mm | Standard Deviation 19.02 |
| Tocilizumab | PGA, Using VAS Score | Week 20 | 28.15 mm | Standard Deviation 20.22 |
| Tocilizumab | PGA, Using VAS Score | Week 24 | 32.63 mm | Standard Deviation 23.44 |
| Tocilizumab | PGA, Using VAS Score | Week 28 | 26.02 mm | Standard Deviation 18.79 |
| Tocilizumab | PGA, Using VAS Score | Week 32 | 27.08 mm | Standard Deviation 20.98 |
| Tocilizumab | PGA, Using VAS Score | Week 36 | 30.79 mm | Standard Deviation 22.37 |
| Tocilizumab | PGA, Using VAS Score | Week 40 | 30.50 mm | Standard Deviation 21.93 |
| Tocilizumab | PGA, Using VAS Score | Week 44 | 25.79 mm | Standard Deviation 16.33 |
| Tocilizumab | PGA, Using VAS Score | Week 48 | 23.86 mm | Standard Deviation 19.11 |
| Tocilizumab | PGA, Using VAS Score | Week 52 | 23.08 mm | Standard Deviation 17.08 |
Secondary
Soluble Interleukin-6 Receptor (sIL-6R) Levels
Time frame: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 1 | 39450 nanograms per milliliter (ng/mL) | Standard Deviation 10740 |
| Tocilizumab | Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 12 | 553.43 nanograms per milliliter (ng/mL) | Standard Deviation 120.36 |
| Tocilizumab | Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 24 | 572.03 nanograms per milliliter (ng/mL) | Standard Deviation 136.68 |
| Tocilizumab | Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 36 | 570.78 nanograms per milliliter (ng/mL) | Standard Deviation 139.16 |
| Tocilizumab | Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 52 | 537.73 nanograms per milliliter (ng/mL) | Standard Deviation 152.55 |
| Tocilizumab | Soluble Interleukin-6 Receptor (sIL-6R) Levels | Week 60 | 42850 nanograms per milliliter (ng/mL) | Standard Deviation 13800 |
Secondary
Tocilizumab Serum Levels
Time frame: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
Population: Full analysis set. Here, Number analyzed = number of participants analyzed for this outcome measure at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tocilizumab | Tocilizumab Serum Levels | Week 1 | 0.38 microgrms per milliliter (mcg/mL) | Standard Deviation 0.17 |
| Tocilizumab | Tocilizumab Serum Levels | Week 12 | 41.98 microgrms per milliliter (mcg/mL) | Standard Deviation 25.04 |
| Tocilizumab | Tocilizumab Serum Levels | Week 24 | 44.67 microgrms per milliliter (mcg/mL) | Standard Deviation 28.83 |
| Tocilizumab | Tocilizumab Serum Levels | Week 36 | 47.90 microgrms per milliliter (mcg/mL) | Standard Deviation 28.29 |
| Tocilizumab | Tocilizumab Serum Levels | Week 52 | 45.37 microgrms per milliliter (mcg/mL) | Standard Deviation 28.13 |
| Tocilizumab | Tocilizumab Serum Levels | Week 60 | 6.46 microgrms per milliliter (mcg/mL) | Standard Deviation 4.28 |